CN101010276B

CN101010276B - Novel cyclohexane derivative, prodrug thereof and salt thereof, and therapeutic agent containing the same for diabetes

Info

Publication number: CN101010276B
Application number: CN200580029174XA
Authority: CN
Inventors: 松冈宏治; 佐藤勉; 西本昌弘; 新间信夫
Original assignee: Chugai Pharmaceutical Co Ltd
Current assignee: Chugai Pharmaceutical Co Ltd
Priority date: 2004-07-26
Filing date: 2005-07-26
Publication date: 2011-01-12
Anticipated expiration: 2025-07-26
Also published as: CN101010276A; ZA200700755B

Abstract

A cyclohexane derivative having the function of reducing a blood sugar level and having preferable properties required of medicines, such as long-lasting drug activity, metabolic stability, and safety; and a medicinal composition for use in the prevention or treatment of diseases attributable to hyperglycemia, such as diabetes, e.g., insulin dependent diabetes mellitus (type 1 diabetes) or noninsulin-dependent diabetes mellitus (type 2 diabetes), complications of diabetes, and obesity. The derivative is a compound represented by the formula (I): (wherein A is -O-, -CH2-, or -NH-; nis an integer selected between 0 and 1; R6and R7 each independently is hydrogen or C1-6 alkyl; m is an integer selected among 1-3; Q is selected among the following formulae Q1 to Q5; Ar1 is optionally substituted arylene or optionally substituted heteroarylene, provided that the heteroarylene may be bonded to an aromatic carbocycle or aromatic heterocycle to form a fused ring; and Ar2 is optionally substituted aryl or optionally substituted heteroaryl), a prodrug of the compound, or a pharmaceutically acceptable salt of either. Also provided are a medicine, a medicinal composition, or the like each containing the compound.

Description

Cyclohexane derivant, its prodrug and salt thereof and the remedy for diabetes that contains it

Technical field

The present invention relates to a kind of as medicine useful cyclohexane derivant or its prodrug or their pharmaceutically useful salt.In more detail, in particular, the present invention relates to a kind of Na that can pass through to suppress ⁺-glucose symporter 2 (SGLT2) is used as the prevention or useful cyclohexane derivant and the prodrug and their salt of therapeutical agent of the disease that causes because of hyperglycemia of diabetes, diabetic complication, obesity of insulin-dependent diabetes (type 1 diabetes), Regular Insulin dependent/non-dependent diabetes (diabetes B) etc. etc.

Background technology

In recent years, owing to reasons such as the Occidentalizing of dietetic life, chronic exercise deficiencies, cause the diabetic subject to increase gradually.Among the diabetic subject, because chronic hyperglycemia makes insulin secretion and insulin sensitivity all reduce, this further makes blood glucose value rise, and causes the deterioration of symptom.Up to now, as remedy for diabetes, use biguanide drug, sulfonylurea medicine, glycosidase inhibitor, insulin resistant property improvement medicine etc.But according to reports, biguanide drug has the side effect of lactic acidosis; The sulfonylurea medical instrument has hypoglycemic side effect; Glycosidase inhibitor has the side effect of diarrhoea etc.; Therefore people urgently wish to develop a class the remedy for diabetes with new role mechanism different with these medicines, and this is present present situation.

According to reports, as phlorizin from natural glucose-derivative, be suppressed at the absorption again of superfluous glucose in the kidney by the sodium dependent glucose symporter 2 (SGLT2) that exists in the S1 position that is suppressed near the uriniferous tubules kidney, promote the drainage of glucose, demonstrate the effect (with reference to non-patent literature 1) of lowering blood glucose, hereafter to now, based on the research actively expansion of the remedy for diabetes that suppresses SGLT2.

For example, open 2000-80041 communique (patent documentation 1), international disclose No. 01/068660 (patent documentation 2), international disclosing in No. 04/007517 (patent documentation 3) etc., reported compound as the inhibitor use of SGLT2 the spy.But, the problem that exists is that the compound of putting down in writing in phlorizin and the above-mentioned patent application all has glucose as part-structure, if with they oral administrations at present, then because the Glycosylase that exists etc. and hydrolysis takes place easily in the small intestine, thereby pharmacological action is rapidly disappeared.In addition, according to reports, in the occasion of phlorizin, Phloretin as the aglycon part suppresses to promote the sugar of dispersion pattern to carry body consumingly, for example, and according to reports, if throw to Phloretin to rat vein, the detrimentally affect (for example, with reference to non-patent literature 2) that glucose concn reduces in the brain then can take place.

Therefore, in order to prevent this decomposition, improve assimilated efficiency that people are carrying out compound is transformed into the trial of prodrug.But, throwing the occasion of giving prodrug, wish that this prodrug is in target organ or positively metabolism takes place in its vicinity and change active compound into, but, there are various metabolic enzymes in vivo, and individual difference is very big, often is difficult to the effect that prodrug is played stably.In addition, people are attempting changing the glycosidic bond of compound into C-C (with reference to patent documentation 4～8), require further raising to comprise the characteristic as medicine such as active and metabolic stability.

[patent documentation 1]

The spy opens the 2000-080041 communique

[patent documentation 2]

International No. 01/068660 brochure [パ Application Off レ Star ト] that disclose

[patent documentation 3]

The international brochure that discloses No. 04/007517

[patent documentation 4]

No. the 2001/041674th, U.S. Patent Application Publication

[patent documentation 5]

No. the 2002/137903rd, U.S. Patent Application Publication

[patent documentation 6]

The international brochure that discloses No. 01/027128

[patent documentation 7]

The international brochure that discloses No. 02/083066

[patent documentation 8]

The international brochure that discloses No. 04/013118

[non-patent literature 1]

J.Clin.Invest., the 93rd the volume, the 1037th page, 1994 years

[non-patent literature 2]

Stroke, the 14th volume, the 388th page, nineteen eighty-three

Summary of the invention

The objective of the invention is to, a kind of cyclohexane derivant that has good characteristic as medicine is provided.Another object of the present invention is, provides a kind of and particularly has blood sugar reduction effect, and then have the cyclohexane derivant as the good characteristic of medicine such as drug effect persistence, metabolic stability or security.And then, a further object of the present invention is, the pharmaceutical composition of the disease that causes because of hyperglycemia of a kind of diabetes that are used for prevention or treatment insulin-dependent diabetes (type 1 diabetes), Regular Insulin dependent/non-dependent diabetes (diabetes B) etc., diabetic complication, obesity etc. is provided.

In order to achieve the above object, the present inventor has carried out meticulous research, and the result has obtained having good SGLT2 by the cyclohexane derivant that formula (I) is represented and suppressed active knowledge, so far finishes the present invention.

That is,, provide cyclohexane derivant or its prodrug or their pharmaceutically useful salt by formula (I) expression according to 1 aspect of the present invention:

[changing 1]

[in the formula, A is-O-,-CH ₂-or-NH-;

The integer of n for from 0 and 1, selecting;

R ⁶And R ⁷Be hydrogen atom or C independently of one another ₁-C ₆Alkyl;

The integer of m for from 1～3, selecting;

Q is selected from the Q that is expressed from the next ¹～Q ⁵:

[changing 2]

R ¹, R ², R ³, R ⁴And R ⁵The C that be selected from hydrogen atom, hydroxyl independently of one another, can be replaced by the Ra more than 1 ₁-C ₆Alkyl, the C that can be replaced by the Ra more than 1 ₁-C ₆Alkoxyl group, the C that can be replaced by the Rb more than 1 ₇-C ₁₄Aralkoxy and-OC (=O) Rx;

Rx is can be by the C of the replacement of the Ra more than 1 ₁-C ₆Alkyl, the aryl that can be replaced by the Rb more than 1, the heteroaryl that can be replaced by the Rb more than 1, the C that can be replaced by the Ra more than 1 ₁-C ₆Alkoxyl group or-NReRf;

Ar ¹Be the arylidene that can be replaced by the Rb more than 1 or the heteroarylidene that can be replaced by the Rb more than 1, this heteroarylidene also can form condensed ring with aromatic carbon ring or heteroaromatic;

Ar ²Be the aryl that can be replaced by the Rb more than 1 or the heteroaryl that can be replaced by the Rb more than 1;

The C that Ra is selected from halogen atom, hydroxyl, cyano group, nitro, carboxyl independently of one another, can be replaced by the Rc more than 1 ₁-C ₆Alkoxyl group, the aryl that can be replaced by the Rd more than 1, the aryloxy that can be replaced by the Rd more than 1, the heteroaryl that can be replaced by the Rd more than 1, heteroaryloxy, sulfydryl, the C that can be replaced by the Rd more than 1 ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulfinyl, C ₁-C ₆Alkyl sulphonyl ,-NRfRg and the C that can be replaced by the Rc more than 1 ₁-C ₆Alkyl-carbonyl;

Rb is selected from independently of one another can be by the C of the replacement of the Rc more than 1 ₁-C ₆Alkyl, the C that can be replaced by the Rc more than 1 ₁-C ₆Alkenyl, the C that can be replaced by the Rc more than 1 ₃-C ₈Cycloalkyl, the C that can be replaced by the Rd more than 1 ₇-C ₁₄Aralkyl, halogen atom, hydroxyl, cyano group, nitro, carboxyl, the C that can be replaced by the Rc more than 1 ₁-C ₆Alkoxyl group, the aryl that can be replaced by the Rd more than 1, the aryloxy that can be replaced by the Rd more than 1, the heteroaryl that can be replaced by the Rd more than 1, heteroaryloxy, sulfydryl, the C that can be replaced by the Rd more than 1 ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulfinyl, C ₁-C ₆Alkyl sulphonyl ,-NRfRg, the C that can be replaced by the Rc more than 1 ₁-C ₆Alkyl-carbonyl, C ₁-C ₃Alkylene dioxo base, heterocyclic radical ,-CO ₂Ri and-CONRiRj;

The C that Rc is selected from halogen atom, hydroxyl, cyano group, nitro, carboxyl independently of one another, can be replaced by the halogen atom more than 1 ₁-C ₆Alkoxyl group, the aryl that can be replaced by the Rd more than 1, the aryloxy that can be replaced by the Rd more than 1, the heteroaryl that can be replaced by the Rd more than 1, heteroaryloxy, amino, the C that can be replaced by the Rd more than 1 ₁-C ₆Alkylamino and two (C ₁-C ₆Alkyl) amino;

Rd is selected from independently of one another can be by the C of the replacement of the halogen atom more than 1 ₁-C ₆Alkyl, the C that can be replaced by the halogen atom more than 1 ₁-C ₆Alkoxyl group, the C that can be replaced by the halogen atom more than 1 ₇-C ₁₄Aralkyl, halogen atom, hydroxyl, cyano group, nitro, amino, C ₁-C ₆Alkylamino and two (C ₁-C ₆Alkyl) amino;

The C that Re is hydrogen atom, can be replaced by the Rc more than 1 ₁-C ₆Alkyl, the aryl that can be replaced by the Rd more than 1 or the heteroaryl that can be replaced by the Rd more than 1;

Rf is the hydrogen atom or the C that can be replaced by the Rc more than 1 ₁-C ₆Alkyl;

The C that Rg is hydrogen atom, can be replaced by the Rc more than 1 ₁-C ₆Alkyl, the C that can be replaced by the Rc more than 1 ₁-C ₆Alkyl-carbonyl, the aryl that can be replaced by the Rd more than 1, the heteroaryl that can be replaced by the Rd more than 1, formamyl, the C that can be replaced by the Rc more than 1 ₁-C ₆Alkoxy carbonyl or the C that can be replaced by the Rc more than 1 ₁-C ₆Alkyl sulphonyl; Perhaps

Re with Rf and Rf and Rg also can with the nitrogen-atoms of their institute's bondings, form 4～7 yuan of heterocycles;

The C that Ri and Rj are selected from hydrogen atom independently of one another, can be replaced by the Rc more than 1 ₁-C ₆Alkyl, the C that can be replaced by the Rc more than 1 ₃-C ₈Cycloalkyl and the C that can be replaced by the Rd more than 1 ₇-C ₁₄Aralkyl].

According to a further aspect in the invention, providing n is 1 cyclohexane derivant or its prodrug or their pharmaceutically useful salt by formula (I) expression.Herein, A be preferably-O-or-NH-.In addition, at Ar ¹On the replacement mode preferably, substituting group-(CR ⁶R ⁷) _m-Ar ²Being bonded to bonding has on the adjacent annular atoms of the annular atoms of substituent A, for example at Ar ¹Be the occasion of phenylene, preferred ortho position replaces body; In addition, for example at Ar ¹Be the occasion of inferior thienyl, preferred 2,3 replace or 3,4 replacements; And then, for example at Ar ¹Be the occasion of pyridylidene [pyridinylene], preferred 2,3 replacements, 3,4 replace, 4,5 replacements or 5,6 replace.In addition, at Ar ¹Be the occasion of inferior pyrazolyl [pyrazolylene], preferred 3,4 replacements, 4,5 replace or 1,5 replacement.Substituent A and substituting group-(CR should be described ⁶R ⁷) _m-Ar ²Also can with the theheterocyclic nitrogen atom bonding.

According to other aspects of the invention, providing n is 0 cyclohexane derivant or its prodrug or their pharmaceutically useful salt by formula (I) expression.Herein, at Ar ¹On the replacement mode preferably, substituting group-(CR ⁶R ⁷) _m-Ar ²Be bonded to from bonding have the annular atoms of Q leave the ring of 2 atoms former on, for example at Ar ¹Be the occasion of phenylene, preferred between the position replace body; In addition, for example at Ar ¹Be the occasion of pyridylidene, preferred 2,4 replacements, 3,5 replace, 4,6 replacements or 1,6 replace; And then, for example at Ar ¹Be the occasion of inferior indyl [indolylene], preferred 1,3 replacement, 3,4 replaces, 4,6 replacements or 5,7 replace.In addition, at Ar ¹Be the occasion of inferior pyrazolyl, preferred 1,3 replacement, 3,5 replaces or 1,4 replacement.Substituent A and substituting group-(CR should be described ⁶R ⁷) _m-Ar ²Also can with the theheterocyclic nitrogen atom bonding.

In above-mentioned formula (I), m is preferably 1.In addition, Ar ¹Be preferably phenylene, naphthylidene, inferior thienyl, pyridylidene, inferior indyl or inferior pyrazolyl, be preferably phenylene, inferior thienyl, pyridylidene or inferior indyl (these groups also can be replaced by the Rb more than 1) especially.

In above-mentioned formula (I), m is preferably 1, in addition, and Ar ²Be preferably phenyl, naphthyl, thienyl, benzofuryl, benzothienyl, Ben Bing Er Evil cyclopentadienyl [benzodioxolyl], 2,3-dihydro benzo furyl or 2,3-dihydrobenzo thienyl, be preferably phenyl, Ben Bing Er Evil cyclopentadienyl or 2 especially, 3-dihydro benzo furyl (these groups also can be replaced by the Rb more than 1).

At above-mentioned formula Q ¹～Q ⁵In, R ¹, R ², R ³, R ⁴, and R ⁵Preferably independently of one another for be selected from hydroxyl and-the OC (=O) group of Rx.

According to other aspects of the invention, provide that a kind of m is 1, n is 1, A for-O-or-NH-, Ar ¹Be selected from phenylene, naphthylidene, inferior thienyl, pyridylidene, inferior indyl or inferior pyrazolyl (these groups can be replaced by the Rb more than 1), Ar ²Be phenyl, naphthyl, thienyl, benzofuryl, benzothienyl, Ben Bing Er Evil cyclopentadienyl, 2,3-dihydro benzo furyl or 2,3-dihydrobenzo thienyl (these groups can be replaced by the Rb more than 1), R ¹, R ², R ³, R ⁴, and R ⁵Be selected from independently of one another hydroxyl and-OC (=O) compound Rx, above-mentioned formula (I) or its prodrug or their pharmaceutically useful salt.

According to other aspects of the invention, provide that a kind of m is 1, n is 0, Ar ¹Be phenylene, naphthylidene, inferior thienyl base, pyridylidene, inferior indyl or inferior pyrazolyl (these groups can be replaced by the Rb more than 1), Ar ²Be phenyl, naphthyl, thienyl, benzofuryl, benzothienyl, Ben Bing Er Evil cyclopentadienyl, 2,3-dihydro benzo furyl or 2,3-dihydrobenzo thienyl (these groups can be replaced by the Rb more than 1), R ¹, R ², R ³, R ⁴, and R ⁵Be selected from independently of one another hydroxyl and-OC (=O) compound Rx, above-mentioned formula (I) or its prodrug or their pharmaceutically useful salt.

And then, according to other aspects of the invention, provide compound or its prodrug or their the pharmaceutically useful salt from following, selected:

[2-(4-methoxy-benzyl) phenyl]-5a-carbon [carba]-β-D-glucopyranoside [グ Le コピラノシ De glucopyranoside];

[1S, 2R, 3R, 4R, 6S]-4-methylol-6-[3-(4-methoxy-benzyl) phenyl] hexanaphthene-1,2, the 3-triol;

[2-(4-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclopentyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-benzyl chloride base) phenyl]-5a-carbon-β-D-glucopyranoside;

(2-benzyl phenyl)-5a-carbon-β-D-glucopyranoside;

[2-(4-isopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-n-propyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methyl sulfane base [sulfanyl] benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[3-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-p-methoxy-phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-6-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-fluorophenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[5-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methyl sulphonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3, the 4-dimethoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-hydroxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyano group benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-aminomethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[5-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxycarbonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-formamyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-N, N-formyl-dimethylamino benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-ethoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-difluoro-methoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-tertiary butyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-yl]-5a-carbon-β-D-glucopyranoside;

[3-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-3-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside; And

[2-(3-fluoro-4-methoxy-benzyl) phenyl]-5a-carbon-α-D-glucopyranoside;

[4-(4-cyclopropyl benzyl) pyridin-3-yl]-5a-carbon-β-D-glucopyranoside;

[2-(4-carboxyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-vinyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

2-[4-(2,2-difluoroethylene base) benzyl] phenyl }-5a-carbon-β-D-glucopyranoside;

[2-(2,3-Dihydrobenzofuranes-5-ylmethyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-fluoro-4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxyl group-3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-pyrazol-1-yl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-chloro-4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3, the 4-methylenedioxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclobutyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-ethanoyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-5-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside;

[2-(thionaphthene-2-yl) aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

(R)-2-[1-(4-cyclopropyl phenyl) ethyl] phenyl }-5a-carbon-β-D-glucopyranoside;

(S)-2-[1-(4-cyclopropyl phenyl) ethyl] phenyl }-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclopropyl benzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside;

[5-chloro-2-(4-cyclopropyl benzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside;

(1R, 2S, 3R, 6R)-6-[2-(4-cyclopropyl benzyl) phenoxy group]-4-(methylol) hexamethylene-4-alkene-1,2, the 3-triol;

(1R, 2S, 3R, 6R)-and 4-methylol-6-[2-(4-methoxy-benzyl) phenoxy group] hexamethylene-4-alkene-1,2, the 3-triol;

(1R, 2S, 3S, 6R)-4-[3-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-4-alkene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-and 1-[5-(4-Ethylbenzyl)-2, the 4-Dimethoxyphenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-and 4-[5-(4-Ethylbenzyl)-2, the 4-Dimethoxyphenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-aminomethyl phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-aminomethyl phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-and 1-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl] methylol hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-Trifluoromethoxyphen-l]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-isopropyl benzyl)-2-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-hydroxybenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-hydroxy phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-cyclopropyl benzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol;

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-fluorophenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1S, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-fluorophenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol;

(1S, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4S, 6R)-4-[1-(4-Ethylbenzyl)-1H-indol-3-yl]-6-(methylol) hexamethylene-1,2, the 3-triol.

According to other aspects of the invention, provide a kind of as Na ⁺-glucose symporter inhibitor pharmaceutical composition that use, that contain the compound of above-mentioned formula (I).

According to other aspects of the invention, providing a kind of is used for prevention or treats insulin-dependent diabetes (type 1 diabetes) for example or Regular Insulin dependent/non-dependent diabetes diabetes such as (diabetes Bs), the diabetic complication or pharmaceutical composition obesity, that contain the compound of above-mentioned formula (I) that cause because of hyperglycemia.

According to other aspects of the invention, provide a kind of comprise with effective therapeutic dose of the compound or its salt of above-mentioned formula (I) to patient's administration, insulin-dependent diabetes (type 1 diabetes), Regular Insulin dependent/non-dependent diabetes diabetes such as (diabetes Bs) and the diabetic complication that causes because of hyperglycemia, the prevention or the methods of treatment of obesity.

At above-mentioned formula Q ¹～Q ⁵In, R ¹, R ², R ³, and R ⁴Also can be independently of one another for being selected from for example hydroxyl, C ₁-C ₆Alkoxyl group, C ₇-C ₁₄Aralkoxy or-OC (=O) group of Rx, especially, R ¹, R ², R ³, R ⁴, and R ⁵Preferably be all hydroxyl.

In The compounds of this invention, n is preferably 1, and in this occasion, A is preferably-O-,-NH-, be preferably especially-O-.

In above-mentioned formula (I), Ar ¹And Ar ²Can be replaced by 1～4 substituent R b that selects independently separately; And, be preferably halogen atom as Rb; Hydroxyl; Can be selected from the C that halogen atom, hydroxyl or amino substituting group replace by 1～4 ₁-C ₆Alkyl and C ₃-C ₈Cycloalkyl; Can be selected from the C that halogen atom, hydroxyl or amino substituting group replace by 1～4 ₁-C ₆Alkoxyl group and C ₁-C ₆Alkylthio; Cyano group; C ₁-C ₆Alkyl sulphonyl; Nitro; Carboxyl; (herein, Re is hydrogen atom, C to-NReRf ₁-C ₆Alkyl, C ₁-C ₆Alkyl-carbonyl, formamyl, C ₁-C ₆Alkyl sulphonyl or C ₁-C ₆Carbalkoxy; Rf is hydrogen atom or C ₁-C ₆Alkyl); 5 or 6 yuan of heteroaryls; Perhaps 4～6 yuan of heterocyclic radicals.

By Ar ¹In the group of expression, arylidene is meant by aromatic carbon ring, preferably contain the divalent group that carbon number is 6～10 aromatic carbon ring, comprises for example phenylene, naphthylidene etc.Heteroarylidene is meant the divalent group that contains heteroaromatic, preferred 6～10 yuan heteroaromatic, comprises heteroarylidene that contains for example pyrrole ring, indole ring, thiphene ring, thionaphthene ring, furan nucleus, cumarone ring, pyridine ring, quinoline ring, isoquinoline 99.9 ring, thiazole ring, benzothiazole ring, isothiazole ring, benzisothiazole ring, pyrazoles ring, indazole Huan, oxazole ring, benzoxazole ring, isoxazole ring, benzoisoxazole ring, imidazole ring, benzoglyoxaline ring, triazole ring, benzotriazole ring, pyrimidine ring, uridylic ring, pyrazine ring, pyridazine ring etc.Especially, Ar ¹Preferred phenylene, naphthylidene or contain the heteroarylidene of pyridine ring, pyrrole ring, indole ring, thiphene ring, thionaphthene ring, furan nucleus, cumarone ring, pyrazoles ring, more preferably phenylene, inferior thienyl, pyridylidene and inferior indyl.

By Ar ²In the group of expression, aryl is meant phenyl, naphthyl, Azulene base [azulenyl]; Heteroaryl is meant pyrryl, indyl, pyridyl, quinolyl, isoquinolyl, thienyl, benzothienyl, furyl, benzofuryl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazole base, pyrazolyl, indazolyl, oxazolyl, benzoxazolyl, isoxazolyl, benzoisoxazole base, imidazolyl, benzimidazolyl-, triazolyl, benzotriazole base, pyrimidyl, uracil base, pyrazinyl, pyridazinyl etc.; Ar ²Be preferably phenyl, naphthyl, thienyl, benzothienyl, Ben Bing Er Evil cyclopentadienyl, furyl, benzofuryl or 2,3-dihydro benzo furyl, more preferably phenyl, Ben Bing Er Evil cyclopentadienyl or 2,3-dihydro benzo furyl.

In this specification sheets, " C ₁-C ₆Alkyl " be meant straight chain shape, the catenate alkyl of carbon number 1～6; for example comprise methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, 3-methyl butyl, 2-methyl butyl, 1-methyl butyl, 1-ethyl propyl, n-hexyl, 4-methyl amyl, 3-methyl amyl, 2-methyl amyl, 1-methyl amyl, 3-ethyl-butyl and 2-ethyl-butyl etc.As preferred C ₁-C ₆Alkyl can list the alkyl of a straight chain shape for example or a catenate carbon number 1～3, special preferable methyl, ethyl.

In this specification sheets, " C ₃-C ₈Cycloalkyl " be meant and the cyclic alkyl of carbon number 3～8 for example comprise cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group etc.

In this specification sheets, " C ₁-C ₆Alkoxyl group " be meant the alkoxyl group of alkyl that has the straight or branched of carbon number 1～6 as moieties; for example comprise methoxyl group, oxyethyl group, positive propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert.-butoxy, n-pentyloxy, 3-methyl butoxy, 2-methyl butoxy, 1-methyl butoxy, 1-ethyl propoxy-, positive hexyloxy, 4-methyl pentyloxy, 3-methyl pentyloxy, 2-methyl pentyloxy, 1-methyl pentyloxy, 3-ethyl butoxy etc.

In this specification sheets, " aryl " is meant the aryl of the aromatic hydrocarbyl with carbon number 6～10, for example comprises phenyl, 1-naphthyl and 2-naphthyl etc.

In this specification sheets, " C ₇-C ₁₄Aralkyl " be meant that the carbon number that contains aryl defined above is 7～14 aralkyl, for example be meant benzyl, 1-styroyl, 2-styroyl, 1-naphthyl methyl, 2-naphthyl methyl etc.

In this specification sheets, " C ₇-C ₁₄Aralkoxy " be meant contain aralkyl defined above, carbon number is 7～14 aralkoxy, for example, benzyloxy, 1-benzene oxyethyl group, 2-benzene oxyethyl group, 1-naphthyl methoxyl group, 2-naphthyl methoxyl group etc.

In this specification sheets, " heteroaryl " is meant heteroatomic 5～10 yuan of aromatic heterocycles that are independently selected from Sauerstoffatom, nitrogen-atoms and sulphur atom that contain more than 1, for example comprise furyl, thienyl, pyrryl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazole base, thiadiazolyl group, triazolyl, tetrazyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, indyl, quinolyl, isoquinolyl etc.Preferred heteroaryl is 5～6 yuan of heteroaryls of pyrryl, pyrazolyl, imidazolyl, pyridyl etc., preferred especially pyrazolyl.

In this specification sheets, " aryloxy " is meant the aryloxy that has the aromatic hydrocarbyl of carbon number 6～10 defined above as aryl moiety, for example comprises phenoxy group, 1-naphthyloxy and 2-naphthyloxy etc.

In this specification sheets, " heteroaryloxy " is meant to have to contain as heteroaryl moieties and defined abovely is selected from Sauerstoffatom more than 1 or 1, the heteroaryloxy of heteroatomic 5～10 yuan of aromatic heterocycles of nitrogen-atoms and sulphur atom, for example comprise furans oxygen base, thiophene oxy, pyrroles's oxygen base, imidazoles oxygen base, pyrazoles oxygen base oxazole oxygen base isoxazole oxygen base, thiazole oxygen base, isothiazole oxygen base oxadiazole oxygen base, thiadiazoles oxygen base, triazole oxygen base, tetrazolium oxygen base, pyridyloxy, 2-pyrimidinyl oxy, pyrazine oxygen base, pyridazine oxygen base, indoxyl, quinoline oxy (キノリニ Le オキシ), isoquinoline 99.9 oxygen base etc.Preferred heteroaryloxy is 5～6 yuan of ring heteroaryloxies.

In this specification sheets, " C ₁-C ₆Alkylamino " be meant the alkylamino of alkyl that has the straight or branched of carbon number 1～6 as moieties; for example comprise methylamino-, ethylamino, n-propylamine base, isopropylamino, n-butyl amine base, Zhong Ding amino, isobutyl amino, uncle's fourth amino, pentylamine base, 3-methyl fourth amino, 2-methyl fourth amino, 1-methyl fourth amino, 1-ethyl third amino, just oneself amino, 4-methylpent amino, 3-methylpent amino, 2-methylpent amino, 1-methylpent amino, 3-ethyl fourth amino and 2-ethyl fourth amino etc.

In this specification sheets, " two (C ₁-C ₆Alkyl) amino " be meant to have 2 dialkyl amidos as the alkyl of the straight or branched of the carbon number 1～6 of moieties, the part of these 2 alkyl can be identical or different.Should " two (C ₁-C ₆Alkyl) amino " in; for example comprise dimethylamino, diethylin, two n-propylamine bases, diisopropylaminoethyl, two n-butyl amine bases, methyl-n-butyl amine base, methyl-Zhong Ding amino, methyl-isobutyl amino, methyl-uncle's fourth amino, ethyl-n-butyl amine base, ethyl-Zhong Ding amino, ethyl-isobutyl amino and ethyl-uncle's fourth amino etc.

In this specification sheets, " C ₁-C ₆Alkylthio " be meant the alkylthio of alkyl that has the straight or branched of carbon number 1～6 as moieties; for example comprise methylthio group, ethylmercapto group, positive rosickyite base, iprotiazem base, positive butylthio, secondary butylthio, isobutyl sulfenyl, uncle's butylthio, positive penta sulfenyl, 3-methyl butylthio, 2-methyl butylthio, 1-methyl butylthio, 1-ethyl rosickyite base, just own sulfenyl, 4-methylpent sulfenyl, 3-methylpent sulfenyl, 2-methylpent sulfenyl, 1-methylpent sulfenyl, 3-ethyl butylthio and 2-ethyl butylthio etc.

In this specification sheets, " C ₁-C ₆The alkyl sulfinyl " be meant as moieties have carbon number 1～6 straight or branched alkyl the alkyl sulfinyl (SO-R); for example comprise methyl sulfinyl; the ethylsulfinyl-1 base; the n-propyl sulfinyl; the sec.-propyl sulfinyl; the normal-butyl sulfinyl; the sec-butyl sulfinyl; the isobutyl-sulfinyl; tertiary butyl sulfinyl; the n-pentyl sulfinyl; 3-methyl butyl sulfinyl; 2-methyl butyl sulfinyl; 1-methyl butyl sulfinyl; 1-ethyl propyl sulfinyl; the n-hexyl sulfinyl; 4-methyl amyl sulfinyl; 3-methyl amyl sulfinyl; 2-methyl amyl sulfinyl; 1-methyl amyl sulfinyl; 3-ethyl-butyl sulfinyl and 2-ethyl-butyl sulfinyl etc.

In this specification sheets, " C ₁-C ₆Alkyl sulphonyl " be meant the alkyl sulphonyl of alkyl that has the straight or branched of carbon number 1～6 as moieties; for example comprise methyl sulphonyl; ethylsulfonyl; the n-propyl alkylsulfonyl; the sec.-propyl alkylsulfonyl; the normal-butyl alkylsulfonyl; the sec-butyl alkylsulfonyl; the isobutyl-alkylsulfonyl; tertiary butyl alkylsulfonyl; the n-pentyl alkylsulfonyl; 3-methyl butyl alkylsulfonyl; 2-methyl butyl alkylsulfonyl; 1-methyl butyl alkylsulfonyl; 1-ethyl propyl alkylsulfonyl; the n-hexyl alkylsulfonyl; 4-methyl amyl alkylsulfonyl; 3-methyl amyl alkylsulfonyl; 2-methyl amyl alkylsulfonyl; 1-methyl amyl alkylsulfonyl; 3-ethyl-butyl alkylsulfonyl and 2-ethyl-butyl alkylsulfonyl etc.

In this specification sheets, " OC (=O)-Rx " in for example comprise C ₁-C ₆Alkyl carbonyl oxy [alkylcarbonyloxy group], C ₇-C ₁₄Aralkyl carbonyl oxygen base, C ₁-C ₆Alkoxyl group carbonyl oxygen base, C ₇-C ₁₄Aralkoxy carbonyl oxygen base etc.Herein, as C ₁-C ₆Alkyl carbonyl oxy can list acetoxyl group, propionyloxy, butyryl acyloxy, new pentane acyloxy etc., preferred especially acetoxyl group.As C ₇-C ₁₄Aralkyl carbonyl oxygen base can list benzyl carbonyl oxygen base, naphthyl methyl carbonyl oxygen base etc., preferred benzyl carbonyl oxygen base.

As C ₁-C ₆Alkoxyl group carbonyl oxygen base can list methoxyl group carbonyl oxygen base, oxyethyl group carbonyl oxygen base etc., preferred methoxyl group carbonyl oxygen base.As C ₇-C ₁₄Aralkoxy carbonyl oxygen base can list benzyloxy carbonyl oxygen base, naphthyl methoxyl group carbonyl oxygen base etc., preferred benzyloxy carbonyl oxygen base.

In this specification sheets,, can list for example fluorine atom, chlorine atom, bromine atoms and iodine atom etc. as halogen atom.

In this specification sheets, 4～7 yuan of heterocycles be meant can be saturated fully also can fractional saturation or undersaturated fully, can contain 1 above nitrogen-atoms and and then contain the heteroatomic heterocycle that is independently selected from Sauerstoffatom, nitrogen-atoms and sulphur atom more than 1, for example comprise, azetidine, tetramethyleneimine, piperidines, morpholine etc., preferred especially piperidines.

In this specification sheets, " aromatic carbon ring " is meant 6～10 yuan aromatic carbon ring, comprises for example phenyl ring and naphthalene nucleus etc.

In this specification sheets, " heteroaromatic " is meant to contain more than 1 and is independently selected from Sauerstoffatom, heteroatomic 5～6 yuan heteroaromatic of nitrogen-atoms and sulphur atom comprises for example pyrrole ring, indole ring, thiphene ring, the thionaphthene ring, furan nucleus, the cumarone ring, pyridine ring, the quinoline ring, the isoquinoline 99.9 ring, thiazole ring, the benzothiazole ring, the isothiazole ring, the benzisothiazole ring, the pyrazoles ring, indazole ring oxazole ring benzoxazole ring isoxazole ring, the benzoisoxazole ring, imidazole ring, the benzoglyoxaline ring, triazole ring, the benzotriazole ring, pyrimidine ring, the uridylic ring, the pyrazine ring, pyridazine ring etc.

In this specification sheets, " heterocyclic radical " be meant can be saturated fully also can fractional saturation or undersaturated fully, contain and be independently selected from Sauerstoffatom, heteroatomic 4～7 yuan heterocyclic radical in nitrogen-atoms and the sulphur atom more than 1, for example comprise azelidinyl, pyrrolidyl, piperidyl, piperazinyl, pyrryl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl oxazolinyl, morpholinyl, thio-morpholinyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, hexamethyleneimino, furyl, tetrahydrofuran base, thienyl, tetrahydro-thienyl, dioxolanyl, oxygen Thiophane base (オキサチオラニ Le) alkyl dioxin etc.The link position of this heterocyclic radical is not so long as can just have particular determination on the carbon atom or the position that replaces on nitrogen-atoms.

In this specification sheets, " C ₁-C ₃Alkylene dioxo base " be by formula-O-(C ₁-C ₃Alkylidene group)-and divalent group that O-represents, comprise for example methylene-dioxy, ethylenedioxy, dimethylated methylene dioxy base etc.

In addition, in the The compounds of this invention, comprise the mixture and the isolating isomer of various steric isomers such as tautomer, optical isomer.

Compound of the present invention forms acid salt sometimes.And, according to the difference of substituting group kind, also may form salt sometimes with alkali.As this salt, can list particularly and mineral acids such as hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, sulfuric acid, nitric acid, phosphoric acid; Organic acids such as formic acid, acetate, propionic acid, oxalic acid, propanedioic acid, succsinic acid, fumaric acid, toxilic acid, lactic acid, oxysuccinic acid, tartrate, citric acid, methylsulfonic acid, ethyl sulfonic acid; The acid salt of acidic amino acid such as aspartic acid, L-glutamic acid.In addition, the salt as forming with alkali can list the salt that forms with mineral alkalis such as sodium, potassium, magnesium, calcium, aluminium; Salt with organic basess formation such as methylamine, ethamine, thanomins; Salt and ammonium salt with basic aminoacidss formation such as Methionin, ornithines.

And then, in the compound of the present invention, also comprise hydrate, pharmaceutically useful various solvates and polymorphic form etc.

Should illustrate that compound of the present invention is not limited to the compound of putting down in writing among the following embodiment, but comprise whole cyclohexane derivant and pharmaceutically useful salt thereof by above-mentioned formula (I) expression.

In addition, among the present invention, also comprise the so-called prodrug that belongs to metabolism in vivo and change the compound of above-mentioned formula (I) into and change the compound of its pharmaceutically useful salt into.As the group of the prodrug that forms The compounds of this invention, can list the group of record in Prog.Med. the 5th volume, 2157-2161 page or leaf (1985) and the group of in wide river bookstore nineteen ninety periodical " exploitation of medicine " the 7th volume molecular designing 163-198 page or leaf, putting down in writing.

Compound of the present invention can adopt various known synthesis methods to prepare according to the feature based on its basic framework or substituent kind.At this moment; difference according to functional group's kind; sometimes it is preferred this protective group being got up on technology of preparing with suitable protecting group in the stage of raw material or intermediate, removes this protecting group then in subsequent handling, so just can obtain desirable compound.As the functional group that needs protection in the preparation section; can list for example hydroxyl and carboxyl etc.; as above-mentioned protecting group, can list the protecting group of record among " the Protective Groups in Organic Synthesis " the 2nd edition of Greene and Wuts work for example.About the introducing of employed protecting group and protecting group with the reaction conditions when removing, also can select based on technique known such as above-mentioned document are suitable.

Compound of the present invention have to kidney in glucose absorb relevant sodium dependent glucose again for the inhibition activity of carrying body 2 (SGLT2) (J.Clin.Invest., the 93rd volume, the 397th page, 1994).Because SGLT2 is suppressed, the absorption again of sugar is suppressed, thereby unnecessary sugar is excreted, so can increase the load of pancreatic beta cell, by make hyperglycemia recover normally to reach the effect of treatment diabetes and improve the synalbumin resistivity effect.

Therefore,, provide a kind of and for example be used for prevention or treatment according to 1 aspect of the present invention, the medicine of diabetes, diabetes relative disease and diabetic complications, this medicine can improve disease or state by the activity that suppresses SGLT2.

Herein, " diabetes " comprise type 1 diabetes, diabetes B, because the diabetes of the other types that specific reasons causes.In addition, " diabetes relative disease " comprises for example obesity, hyperinsulinemia, abnormal carbohydrate metabolism, hyperlipidemia, hypercholesterolemia, high Witepsol W-S 55 mass formed by blood stasis, abnormalities of sugar/lipid metabolism, hypertension, congestive heart failure, edema, hyperuricemia, gout etc.

In addition, " diabetic complications " comprises any of acute complication and chronic complication.As " acute complication ", for example can list hyperglycemia (in the blood ketoacidosis etc.), infect sick (skin, soft tissue, biliary system, respiratory system, urinary tract infections etc.) etc.; As " chronic complication ", can list microangiopathy (ephrosis, retinopathy), arteriosclerosis (atherosclerotic arteriosclerosis, myocardial infarction, cerebral infarction, artery of lower extremity obturation etc.), DPN (sensory nerve, motorius, autonomic nerve etc.), foot gangrene etc.As main diabetic complications, can list diabetic retinopathy, diabetic nephropathy, diabetic neuropathy.

In addition, compound of the present invention also can merge with the remedy for diabetes, diabetic complications curative, hyperlipidaemia curative, hypertension therapeutic medicine etc. of the different mechanisms of action beyond the SGLT2 activity inhibitor and uses.By with compound of the present invention and the combination of other medicaments, can expect that the effect that obtains when treating above-mentioned disease with the single agent of use is compared, merging the effect that can obtain to work in coordination with when using.

As can and " remedy for diabetes; diabetic complications curative " of usefulness; for example can list, insulin sensitivity strengthens medicine (PPAR gamma agonist; PPAR α/gamma agonist; the PPAR delta agonists; PPAR α/gamma/delta agonist etc.); glycosidase inhibitor; biguanide drug; insulin secretion promotes medicine; insulin preparation; the glucagon receptor antagonist; insulin receptor kinase promotes medicine; three peptidyl peptase II inhibitor; inhibitors of dipeptidyl IV; Protein Tyrosine Phosphatases-1B inhibitor; glycogen phosphorylase inhibitors; the G-6-Pase inhibitor; the newborn inhibitor of sugar; the fructose diphosphate enzyme inhibitors; pyruvate dehydrogenase inhibitor; activators of glucokinase; D-hand muscle alcohol; glycogen synthase kinase 3 inhibitor; class glucagon peptide-1; class glucagon peptide-1 analogue; class glucagon peptide-1 agonist; amyrin; the amyrin analogue; the amyrin agonist; glucocorticoid receptor antagonists; the 11beta-Hydroxysteroid dehydrogenase inhibitor; aldose reductase inhibitor; inhibitors of protein kinase C; the gamma-aminobutyric acid receptor antagonist; the sodium channel antagonist; the transcription factor NF-KB inhibitor; the IKK beta inhibitor; the lipid peroxidation enzyme inhibitors; N-acetylize-α-connection-acidity-pepx [N-acetylated-α-linked-acid-dipeptidase] inhibitor; para-insulin growth factor-I; platelet-derived growth factor (PDGF); platelet-derived growth factor (PDGF) analogue; epidermis multiplicaiton factor (EGF); neural growth factor; the carnitine derivative; uridine; 5-hydroxyl-1-methyl glycolylurea; EGB-761; PVC モ Network ロモ Le [bimoclomol]; sulodexide; Y-128; TAR-428 etc.

As remedy for diabetes, diabetic complications curative, can list following those medicaments.

As " biguanide drug ", can list Walaphage, phenformin etc.

As the system of the sulfonylurea in " insulin secretion promotion medicine ", can list for example Glyburide (Glyburide), Glipizide, gliclazide, P-607 etc.; As non-sulfonylurea is to list Na Gelie naphthalene, repaglinide, mitiglinide etc.

" insulin preparation " comprises the gene recombination insulin human and from the Regular Insulin of animal.In addition, according to being divided into 3 classes action time, can list fast-acting type (insulin human, the neutral Regular Insulin of people), osculant (Regular Insulin-people's protamine zinc insulin(PZI) waterborne suspension, the neutral Regular Insulin of people-people's protamine zinc insulin(PZI) waterborne suspension, insulin human's zinc waterborne suspension, zinc insulin waterborne suspension), long-acting type (crystalline human zinc insulin suspension) etc.

As " glycosidase inhibitor ", can list acarbose, voglibose, miglitol etc.

As the PPAR gamma agonist in " insulin sensitivity enhancing medicine ", can list troglitazone, pyrroles's row ketone, Rosiglitazone etc.; As the PPAR alpha/gamma double agonists, can list MK-767 (KRP-297), Tesaglitazar, LM4156, LY510929, DRF-4823, TY-51501 etc.; As the PPAR delta agonists, can list GW-501516 etc.

As " three peptidyl peptase II inhibitor ", can list UCL-139 etc.

As " inhibitors of dipeptidyl IV ", can list NVP-DPP728A, LAF-237, MK-0431, P32/98, TSL-225 etc.

As " aldose reductase inhibitor ", but can list ascorbyl gamolenate, tolrestatin, epalrestat, method ground department he, sorbinil, Statyl, Li Sha he, zenarestat etc.

As " gamma-aminobutyric acid receptor antagonist ", can list topiramate etc.

As " sodium channel antagonist ", can list mexiletine hydrochloride etc.

As " transcription factor NF-KB inhibitor ", can list dexlipotam etc.

As " lipid peroxidation enzyme inhibitors ", can list Tirilazad Mesylate etc.

As " N-acetylize-α-connection-acidity-Dipeptidase inhibitor ", can list GPI-5693 etc.

As " carnitine derivative ", can list carnitine, レバセカ Le ニ Application [levacecarnine] hydrochloric acid [hydrochloric acid レバセカ Le ニ Application] etc.

As can and " hyperlipidaemia curative, the hypertension therapeutic medicine " of usefulness, for example can list 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fibrate, β ₃-adrenoceptor agonists; the AMPK activator; acyl-CoA: chole-sterol acyltransferase inhibitor; probucol (probucol); Tiroidina hormone receptor stimulant; cholesterol absorption inhibitor; lipase inhibitor; microsome Witepsol W-S 55 transporter inhibitors; lipoxygenase inhibitor; the carnitine palmitoyltransferase inhibitor; inhibitor for squalene synthetic enzyme; low density lipoprotein receptor promotor; nicotinic acid derivates; bile acid adsorbent; sodium conjugation bile acid transport (transporter) inhibitor; cholesteryl ester is carried protein inhibitor; angiotensin converting enzyme inhibitor; angiotensin II receptor antagonists; the endothelin converting enzyme inhibitor; endothelin-receptor antagonists; hydragog(ue); calcium antagonist; distensibility of blood vessel depressor; the sympathetic nerve blocking agent; central depressor; α ₂-adrenoceptor agonists, antiplatelet drug, uricogenesis inhibitor, uricosuric agent, urine alkalization medicine, appetite-inhibiting agent, adiponectin receptor stimulant, GPR40 agonist, GPR40 antagonist etc.

As hyperlipidaemia curative, hypertension therapeutic medicine, can list following those medicaments.

As " 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ", can list fluvastatin, lovastatin, Pravastatin, simvastatin, pitavastatin etc.

As " fibrate ", can list bezafibrate, Beclobrate, binifibrate etc.

As " inhibitor for squalene synthetic enzyme ", can list TAK-475, alpha-phosphonosulfonate derivative (No. 5712396 specification sheets of United States Patent (USP)) etc.

As " acyl-CoA: chole-sterol acyltransferase inhibitor ", can list CI-1011, NTE-122, FCE-27677, RP-73163, MCC-147, DPU-129 etc.

As " low density lipoprotein receptor promotion medicine ", can list MD-700, LY-295427 etc.

As " microsome Witepsol W-S 55 transporter inhibitors (MTP inhibitor) ", can list the compound of record in No. 5739135 specification sheets of United States Patent (USP), No. 5712279 specification sheets of United States Patent (USP), No. 5760246 specification sheets of United States Patent (USP) etc.

As " appetite-inhibiting agent ", can list suprarenin norepinephrine agonist (Mazindol, ephedrine etc.), combination of serotonin agonist (the selective serotonin inhibitor of rerecording, for example, fluvoxamine etc.), the plain agonist (sibutramine etc.) of adrenal Serum, melatonin 4 acceptors (MC4R) agonist, alpha-melanophore stimulate hormone (α-MCH), leptin, Cocaine-and amphetamine-regulated transcript (CART) etc.

As " Tiroidina hormone receptor stimulant ", can list methiodide amine sodium, levothyrocine [levothyroxine] sodium etc.

As " cholesterol absorption inhibitor ", can list ezetimibe etc.

As " lipase inhibitor ", can list orlistat etc.

As " carnitine palmitoyltransferase inhibitor ", can list etomoxir etc.

As " nicotinic acid derivates ", can list nicotinic acid, niacinamide, nicomol, Nicoril etc.

As " bile acid adsorbent ", can list Colestyramine, cholestilan, hydrochloric acid コレセベラ system [cholesevelam] etc.

As " angiotensin converting enzyme inhibitor ", can list captopril, enalapril maleate, alacepril, Yipingshu etc.

As " angiotensin-ii receptor antagonistic ", can list candesartan Cilexetil, LOSARTAN POTASSIUM, methylsulfonic acid Eprosartan etc.

As " endothelin converting enzyme inhibitor ", can list CGS-31447, CGS-35066 etc.

As " endothelin-receptor antagonists ", can list L-749805, TBC-3214, BMS-182874 etc.

For example, in the treatment of diabetes etc., preferred consider with The compounds of this invention be selected from insulin sensitivity and strengthen medicine (PPAR gamma agonist, PPAR α/gamma agonist, PPAR delta agonists, PPAR α/gamma/delta agonist etc.), glycosidase inhibitor, biguanide drug, insulin secretion and promote at least a kind of medicament in medicine, insulin preparation and the inhibitors of dipeptidyl IV to merge to use.

In addition, preferred consider with The compounds of this invention be selected from 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fibrate, inhibitor for squalene synthetic enzyme, acetyl-CoA: chole-sterol acyltransferase inhibitor, low density lipoprotein receptor promote at least a kind of medicament in medicine, microsome Witepsol W-S 55 transporter inhibitors and the appetite-inhibiting agent to merge to use.

Medicine of the present invention can be to whole body or local per os or internal rectum, subcutaneous, intramuscular, intravenously, through the non-oral administration of skin etc.

For with compound of the present invention as drug use, can use by any form of solids composition, liquid composition and other composition, can select only form as required.Medicine of the present invention can prepare by fit into pharmaceutically useful carrier in compound of the present invention.Specifically, vehicle commonly used, extender, tackiness agent, disintegrating agent, coating agent, sugar-coat agent, pH be can add and agent, solvating agent or water-based or non-aqueous solvent etc. adjusted, can adopt preparation technique commonly used, be made into tablet, pill, capsule, granule, pulvis, powder, liquor, emulsion, suspension agent, injection, etc.As vehicle, extender, can list for example lactose, Magnesium Stearate, starch, talcum, gelatin, agar, pectin, Sudan Gum-arabic, sweet oil, sesame oil, cocoa cream, ethylene glycol etc. or other vehicle commonly used.

In addition, compound of the present invention can connect compound with formation bags such as α, β or γ-Huan Hujing or methylated cyclodextrin and form preparation.

The dosage of The compounds of this invention, according to the difference of disease, symptom, body weight, age, sex, route of administration etc. and different, for the adult, be preferably the 0.1-1000mg/kg body weight/day, more preferably the 0.1-200mg/kg body weight/day can be pressed compound of the present invention 1 day 1 time or divide administration for several times.

Compound of the present invention can synthesize according to preparation method for example shown below.Should illustrate that in the following flow process, " Bn " represents benzyl.

As 2,3,4 of key intermediate, 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (IV) can prepare below for example like that.

Flow process 1

[changing 3]

Figure 907721DEST_PATH_G18074389150138000D000021

At first; the primary hydroxyl of D-glucal (is for example being protected; protect with t-butyldimethylsilyl) get up after; with 2 secondary hydroxyl benzyl protections, then, the protecting group of removing primary hydroxyl (for example; protecting group is the occasion of t-butyldimethylsilyl; remove with tetrabutyl ammonium fluoride), can synthesize 3 thus, 4-two-O-benzyl-D-glucal (II).

Then, can in 5 operations, change 3,4 into, 6-three-O-benzyl-5a-carbon-D-glucal (III) (Chem.Commun., the 925th page, 1998 years) by compound (II).

Can in 2 operations, change 2,3,4 into, 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (IV) (Liebigs Ann.Chem., the 267th page, nineteen ninety-five) by compound (III).

Compound (V) can adopt the method for document (J.Chem.Soc.Perkin Trans.1, the 3287th page, 1991) record to prepare.Perhaps, shown in following flow process 2, also can be by compound (IV) with suitable oxidising agent (for example, the sensitization DMSO of Swern method etc. or PCC, PDC, Dess-Martin periodinane etc.) preparation compound (V):

Flow process 2

[changing 4]

Compound (IV) can followingly change compound (VII) like that into.

Flow process 3

[changing 5]

Compound (IV) can for example with phenylformic acid carry out light prolong the reaction after be hydrolyzed, deriving is 2,3,4,6-four-O-benzyl-5a-carbon-β-D-Glucopyranose (VI).

Then, by making compound (VI) and suitable halogenating agent (for example, Phosphorus Oxychloride, phosphorus oxybromide, phosphorus trichloride, phosphorus tribromide, tetracol phenixin-triphenylphosphine, carbon tetrabromide-triphenylphosphine, N-chlorosuccinimide [ス Network シニ De succinimide]-triphenylphosphine, N-bromosuccinimide-triphenylphosphine, iodo-triphenylphosphine etc.) have an effect, can prepare the compound that X is a halogen atom (VII).

In addition, in appropriate solvent, under alkaline condition, compound (IV) and methylsulfonyl chloride, Tosyl chloride, Trifluoromethanesulfonic anhydride etc. are had an effect, can prepare X thus is the compound (VII) of methanesulfonyloxy group, tolysulfonyl oxygen base, trifluoromethane sulfonyloxy etc.

For example, as the compound of the following formula of the intermediate of formula (I) compound:

[changing 6]

(VIII)

(in the formula, R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication), can synthesize with reference to following document: international disclose No. 01/68660, international disclose No. 01/074834, international disclose No. 01/074835, internationally disclose No. 02/28872, the world and disclose No. 02/44192, the world and disclose No. 02/064606, the world and disclose No. 03/011880, the world and disclose No. 04/014931.

[changing 7]

(in the formula, R ¹²Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication), can synthesize with reference to following document: international disclosing No. 04/007517.

[changing 8]

(in the formula, R ¹³Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication), can synthesize with reference to following document: international disclose WO01/16147 number, international disclose No. 02/36602, international disclose No. 02/053573, international disclose No. 02/068439, internationally disclose No. 02/068440, the world and disclose No. 02/088157, the world and disclose No. 02/098893, the world and disclose No. 03/020737, the world and disclose No. 03/090783.

[changing 9]

(in the formula, X ¹, X ², X ³And X ⁴Represent nitrogen-atoms or C-R respectively ¹⁴, X ¹, X ², X ³And X ⁴In 1 or 2 be nitrogen-atoms, R ¹⁴Identical with the implication of Rb defined above), can synthesize with reference to following document: international disclosing No. 03/000712.

[changing 10]

(in the formula, R ¹⁵Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication), can be prepared according to for example following flow process 4:

Flow process 4

[changing 11]

(in the formula, R ¹⁶Identical with the implication of Rb defined above, M-alkyl [M-alkyl] and M-aryl [M-aryl] are represented organometallic reagents such as n-Butyl Lithium, phenyl lithium, phenyl-magnesium-bromide respectively; X is halogens such as chlorine, bromine, iodine; Ar ²Identical with above-mentioned implication).

That is, can be by after compound (XIV) and suitable organometallic reagent (n-Butyl Lithium, phenyl lithium, phenyl-magnesium-bromide etc.) be had an effect, make itself and Ar ²-CHO reaction, deriving thus is compound (XV), then, adopts suitable reduction reaction (shortening of use palladium catalyst etc. etc.) to come synthetic.

The compounds of this invention can prepare according to flow process for example shown below 5:

Flow process 5

[changing 12]

(in the formula, R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

Promptly; make compound (IV) and compound (VIII) prolong reaction conditions and carry out condensation, utilize the shortening condition of using palladium catalyst etc. to carry out deprotection then or utilize boron trifluoride-dimethyl thioether etc. to carry out deprotection to prepare according to the light that uses azo agents and phosphine class.Herein, azo agents as can be used in synthetic The compounds of this invention can list azoethane dicarboxylic ester, tetramethyl-azodicarboxy acid amides [カ Le ボキサミ De], 1,6-dimethyl-1,5,7-six hydrogen-1,4,6,7-tetrazo [テトラゾシ Application]-2,5-diketone etc. as the phosphine class, can list triphenylphosphine, tributylphosphine, 2-(dicyclohexyl phosphino-) biphenyl, three (tertiary butyl) phosphine etc.In addition, also can adopt the light that uses positive phosphonate reagent to prolong reaction and synthesize compound of the present invention.Positive phosphonate reagent as using herein can list (cyano group methylene radical) tributyl phosphorane or (cyano group methylene radical) trimethylammonium phosphorane etc.In addition, the substituent R of compound (XVII) ¹¹Perhaps Ar ²Substituting group (, changing into after トリ Off レ one ト [triflate] etc.) in the occasion of halogen or hydroxyl, also can in the presence of palladium catalyst, use tin reagent or boric acid to wait and change.

In addition, compound of the present invention also can prepare according to flow process for example shown below 6:

Flow process 6

[changing 13]

(in the formula, X ⁵Be halogens such as chlorine, bromine, iodine, perhaps leaving group such as methane sulfonate, trifluoromethayl sulfonic acid ester; R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

That is, also can prepare compound (XVI) by making compound (VII) and compound (VIII) in appropriate solvent, under alkaline condition, carry out condensation.As the alkali that can use herein, for example can list sodium hydride, salt of wormwood, potassium tert.-butoxide etc.

In addition, compound of the present invention also can prepare according to flow process for example shown below 7:

Flow process 7

[changing 14]

(in the formula, R ¹¹Identical with the implication of Rb defined above; R " be C ₁-C ₆Alkyl, C ₇-C ₁₄Aralkyl or aryl; Ar ²Identical with above-mentioned implication).

That is, also can adopt and use the light of azo agents and phosphine class to prolong reaction conditions, make compound (IV) and compound (XVIII) condensation after, change alkoxy carbonyl into formyl radical according to ordinary method, make compound (XX), then, make itself and Ar ²-M (M represents the halogenide of lithium, magnesium etc.) has an effect, change compound (XXI) thus into, then, the shortening condition of employing use palladium catalyst etc. etc., hydroxyl and benzyl are removed simultaneously, perhaps with triethyl silicane etc. with the hydroxyl reduction after, remove benzyl with boron trifluoride-dimethyl thioether etc., prepare The compounds of this invention (XVII) thus.

In addition, compound of the present invention also can prepare according to flow process for example shown below 8:

Flow process 8

[changing 15]

(in the formula, X ¹¹The expression halogen atom; R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

That is, also compound (IV) and compound (XXII) can be adopted light prolong reaction and it be derived be compound (XXIII), and then itself and organometallic reagent low alkyl group lithiums such as (etc.) n-Butyl Lithiums are had an effect, and make itself and Ar ²-CHO reacts, thus synthetic compound (XXI).

In addition, compound of the present invention also can prepare according to flow process for example shown below 9:

Flow process 9

[changing 16]

(in the formula, X ²¹And X ²²The expression halogen atom; R " be selected from C independently of one another ₁-C ₆Alkyl; R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

That is, also can have an effect with six alkyl, two tin in the presence of palladium catalyst by making compound (XXIII), deriving is compound (XXIV), makes itself and Ar then ²-CH ₂X ²²In the presence of palladium catalyst, react, thus synthetic compound (XVI).Six alkyl, two tin as using herein can list for example hexa methyl ditin, six dibutyltin dilaurates etc., as palladium catalyst, can list four (triphenyl) phosphine palladium (0), 1,2-two (diphenylphosphino ethane) dichloro palladium (II) etc.

In addition, compound of the present invention also can prepare according to flow process for example shown below 10:

Flow process 10

[changing 17]

(in the formula, R ¹²Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

Promptly, also can adopt and use the light of azo agents and phosphine class to prolong reaction conditions, make compound (IV) and compound (IX) condensation, be derivatized to compound (XXV), then, the shortening condition of employing use palladium catalyst etc. etc. are carried out the reduction of ketone and removing of benzyl simultaneously, perhaps segmentation utilizes the reduction of the ketone that sodium borohydride etc. carries out and utilizes the removing of benzyl of palladium catalyst, prepares The compounds of this invention (XXVI) thus.

In addition, compound of the present invention also can prepare according to flow process for example shown below 11:

Flow process 11

[changing 18]

That is, also can adopt and use the light of azo agents and phosphine class to prolong reaction conditions, make compound (IV) and compound (X) condensation, deriving is compound (XXVII), makes itself and Ar then ²-M (M represents the halogenide of lithium, magnesium etc.) has an effect, change compound (XXI) thus into, then, the shortening condition of employing use palladium catalyst etc. etc., side by side or the piecewise remove hydroxyl and benzyl, prepare compound of the present invention (XXVI) thus.

In addition, compound of the present invention also can prepare according to flow process for example shown below 12:

Flow process 12

[changing 19]

(in the formula, X ⁵Identical with implication defined above, R ¹³Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

That is, compound of the present invention (XXX) also can react in the presence of alkali by making compound (VII) and compound (XI) in appropriate solvent, be derivatized to compound (XXIX), then, the shortening condition of employing use palladium catalyst etc. etc., benzyl is removed, prepared thus.

In addition, in the preparation method of flow process 10, replace compound (IX), can synthesize compound of the present invention (XXXI) (X by using compound (XII) ¹, X ², X ³, X ⁴, and Ar ²With above-mentioned same).

[changing 20]

In addition, compound of the present invention also can prepare according to flow process for example shown below 13:

Flow process 13

[changing 21]

(in the formula, X is a halogen atom; R ¹⁷Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

Promptly, compound of the present invention (XXXV) can prolong reaction by making compound (IV) and phthalic imidine carry out light, make hydrazine then, perhaps methylamine is had an effect, derive and be compound (XXXII), then, by with compound (XXXIII) at palladium catalyst (for example, three (dibenzalacetones), two palladiums (0), 1,1 '-two (diphenylphosphino ferrocene) dichloro palladiums (II) etc.), perhaps (for example at Tong Shiji, cupric iodide (I) etc.) coupled reaction under the existence changes compound (XXXIV) into, then, the shortening condition of employing use palladium catalyst etc. etc. is removed benzyl, prepares thus.

Should illustrate that compound (XXXII) also can prolong reaction by making compound (IV) and sodiumazide etc. carry out light, make itself and triphenylphosphine etc. have an effect to synthesize then.

In addition, compound (XXXIII) can make compound (XXXVI) and Ar according to following flow process 14 ²-M has an effect, and derives to be compound (XXXVII), then in the presence of boron trifluoride-ether coordination compound or trifluoroacetic acid etc., handles with triethyl silicane and to prepare:

Flow process 14

[changing 22]

Figure 838768DEST_PATH_G18074389150138000D000031

(in the formula, X is identical with definition above, R ¹⁷Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

In addition, compound of the present invention also can prepare according to flow process for example shown below 15:

Flow process 15

[changing 23]

Figure 593098DEST_PATH_G18074389150138000D000032

(in the formula, R ¹⁸Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

Promptly, compound (XXXX-I) can be by making compound (XXXVIII) and suitable lithium alkylide (for example, n-Butyl Lithium etc.) have an effect, itself and compound (V) are reacted, the compound (XXXIX-I) that obtains is carried out shortening with palladium catalyst etc. prepare.Similarly; compound (XXXX-II) can be by directly carrying out shortening with compound (XXXIX-II) with palladium catalyst or with hydroxyacetylization; then adopt and use palladium catalyst etc. to carry out catalytic hydrogenation reaction (add as required hydrochloric acid etc. acid), remove acetoxyl group whereby and benzyl prepares.Herein, compound (XXXVIII) can synthesize according to for example international method that discloses record in No. 01/27128.

Compound (XXXX) also can prepare according to the method for flow process shown below 16:

Flow process 16

[changing 24]

(in the formula, X ²³And X ²⁴Be halogen atom; R ¹⁸Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication).

Promptly, can be by making compound (XXXXI) and suitable lithium alkylide (for example, n-Butyl Lithium etc.) have an effect, itself and compound (V) are reacted, derive and be compound (XXXXII), the hydroxyl that generates is changed into after the thiono oxygen base by for example methylthio group carbonylation or imidazoles sulfenyl carbonylation, at suitable radical initiator (for example, 2,2 '-Diisopropyl azodicarboxylate or benzoyl peroxide) existence under, (for example make itself and suitable free radical reaction agent, the stannic hydride reagent of tributyltin hydride etc., the silane reagent of diphenyl silane etc., the condition of diphosphorous acid and diethyl phosphite and tertiary amine combination) has an effect, carry out dehydroxylation thus, thus synthetic compound (XXXXIII).Then, (for example adopt suitable halogenation condition, N-bromosuccinimide, bromine, hydrogen bromide etc.), make it change benzyl halogenide (XXXXIV) into, at suitable palladium catalyst (for example, four (triphenyl) phosphine palladium (0), 1,2-two (diphenylphosphino ethane) dichloro palladium (II) etc.) under the existence, after itself and aryl halide (comprising heteroaryl halogenide) are reacted, carry out debenzylation, deriving thus is compound (XXXX).

Intermediate (XXXXIV) also can prepare according to the method for flow process shown below 17:

Flow process 17

[changing 25]

(in the formula, R ¹⁸Identical with the implication of Rb defined above; P is a protecting group; X is a halogen atom; Ar ²Identical with above-mentioned implication.)

Promptly; by with suitable protecting group (for example with the hydroxyl of compound (XXXXVI); t-butyldimethylsilyl, THP trtrahydropyranyl etc.) protect after; (for example make itself and suitable lithium alkylide; n-Butyl Lithium etc.) have an effect; itself and compound (V) are reacted, and deriving is compound (XXXXVII).Then, change tert-hydroxyl into thiono oxygen base by for example methylthio group thiocarbonylization or imidazoles sulfenyl carbonylation, at suitable radical initiator (for example, 2,2 '-Diisopropyl azodicarboxylate or benzoyl peroxide) existence under, itself and suitable free radical reaction agent (for example, the condition of silane reagent, diphosphorous acid or the diethyl phosphite of the stannic hydride reagent of tributyltin hydride etc., diphenyl silane etc. and tertiary amine combination) are had an effect, change compound (XXXXVIII) thus into.Then, carry out (for example adopting suitable halogenation condition after deprotection obtains compound (XXXXIX); at X is the occasion of bromine atoms; in the presence of triphenylphosphine, use the condition of N-bromosuccinimide, bromine, carbon tetrabromide etc.), can synthetic compound (XXXXIV).

Compound (L) also can prepare according to the method for flow process shown below 18:

Flow process 18

[changing 26]

Figure 330109DEST_PATH_G18074389150138000D000041

(in the formula, R ¹¹Identical with the implication of Rb defined above, Ar ²Identical with above-mentioned implication.)

That is, in the preparation method of flow process 5, replace compound (IV), can prepare compound of the present invention (L) by using compound (LI) or compound (LII).Compound (LI) can adopt document (J.Org.Chem., 63 the volume, 5668 pages, 1998) in the record method synthesize; Compound (LII) can adopt document (Tetrahedron, 56 the volume, 7109 pages, 2000) in the record method synthesize.

In addition, compound of the present invention can prepare according to the method for flow process 19.

Flow process 19

[changing 27]

(in the formula, R ¹⁷Identical with the implication of Rb defined above; X is identical with definition above; Tf is a trifluoromethane sulfonyl group; Ar ²Identical with above-mentioned implication.)

Promptly, by (LIV) that compound (V) トリ Off レ one トization is obtained with act on compound (XXXIII) by the suitable lithium alkylide (n-Butyl Lithium etc.) of use, and with boric acid ester (trimethyl borate etc.) handle and the compound (LVII) that obtains together, in the presence of palladium catalyst (four (triphenyl) phosphine palladium etc.), handle, can obtain compound (LV) thus.Again with it in the presence of pentamethylbenzene etc., handle with boron trichloride etc., can prepare compound (LVI) thus.

The preparation method of The compounds of this invention is not limited to above-mentioned method.Compound of the present invention also can by will be for example in the flow process 1～19 the included suitable combination of operation come synthetic.

Compound of the present invention not only has the SGLT2 restraining effect, and has the good characteristic as medicine, for example metabolic stability, oral absorption, drug effect persistence, security etc.Therefore, according to the present invention, the diabetic complication that a kind of diabetes that are used for insulin-dependent diabetes (type 1 diabetes), Regular Insulin dependent/non-dependent diabetes (diabetes B) etc. can be provided and cause because of hyperglycemia, the prevention or the treatment pharmaceutical composition (particularly treatment), that have blood sugar reduction effect of obesity.

[embodiment]

Below illustrate in greater detail content of the present invention, but the present invention is not subjected to the qualification of these contents with embodiment and test example.

In following embodiment, each suspension points has following implication:

NMR: nuclear magnetic resonance spectrum (mark in the TMS), MS: mass analysis value, HPLC: high performance liquid chromatography.

NMR, MS and HPLC use following instrument to measure:

NMR:JEOL JNM-EX-270 (270MHz), Varian mercury 300 (300MHz) or JEOL JNM-ECP400 (400MHz);

MS:Thermo Finigan LCQ of company or the micromassZQ of Waters company;

HPLC:Waters company 2690/2996 (detector).

The short of specially record of the condition determination of HPLC is following those conditions just.

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Moving phase: carry out wash-out according to be changed to 20 minutes gradient of 0.1%TFA/MeCN (100%) cost from 0.1%TFA/MeCN (5%)+0.1%TFA/H2O (95%), under the same terms (0.1%TFA/MeCN (100%)), carry out 5 minutes wash-outs then.

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

The full wave total discharge curve figure of testing conditions: 230～400nm.

Embodiment 1

[2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) methyl benzoate is synthetic

In the THF solution (400 μ L) of wintergreen oil (72 μ L, 0.557mmol), add triphenylphosphine (146mg, 0.557mmol), 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (200mg, 0.371mmol), drip diethylazodicarboxylate (DEAD, 88 μ L, 0.557mmol), at room temperature stirred 10.5 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 3)) make with extra care, obtain title compound (123mg, 49%).

¹H-NMR(CDCl ₃)δ：1.60-1.80(2H，m)、2.15-2.24(1H，m)、3.48-3.64(4H，m)、3.75-3.90(1H，m)、3.83(3H，s)、4.43(3H，s)、4.53(1H，d，J＝10.7Hz)、4.51-4.98(6H，m)、6.95-7.02(1H，m)、7.10-7.50(22H，m)、7.78(1H，dd，J＝1.65，7.75Hz)

MS(ESI ⁺)：695[M+Na] ⁺

2) 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) benzylalcohol is synthetic

To 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) adds lithium aluminium hydride (10.4mg, 0.274mmol) bit by bit in the THF solution (360 μ L) of methyl benzoate (123mg, 0.183mmol), in oil bath (55 ℃), stirred 3 hours.After reaction solution is cooled to room temperature, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 3)) make with extra care, obtain title compound (95mg, 81%).

¹H-NMR(CDCl ₃)δ：1.60-1.80(2H，m)、2.16-2.22(1H，m)、3.46-3.74(5H，m)、4.43(3H，s)、4.54(1H，d，J＝10.7Hz)、4.66(2H，br?s)、4.81-4.96(5H，m)、6.94-7.31(24H，m)

MS(ESI ⁺)：667[M+Na] ⁺

3) 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) phenyl aldehyde is synthetic

In the dichloromethane solution (1.5mL) of 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) benzylalcohol (95mg, 0.147mmol), add Dess-Martin reagent (94mg, 0.221mmol), at room temperature stirred 45 minutes.From reaction solution, remove by filter insolubles, filtrate decompression is concentrated.With the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 3)) make with extra care, obtain title compound (77mg, 81%).

¹H-NMR(CDCl ₃)δ：1.60-1.80(2H，m)、2.17-2.23(1H，m)、3.48-3.78(5H，m)、4.44(3H，s)、4.54(1H，d，J＝10.7Hz)、?4.73-4.97(5H，m)、7.00-7.32(22H，m)、7.50(1H，dd，J＝1.48，7.83Hz)、7.83(1H，dd，J＝1.49，7.58Hz)、10.4(1H，s)

4) [2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) phenyl]-(4-p-methoxy-phenyl) methyl alcohol is synthetic

To 2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl) adds the THF solution (480 μ L, 0.238mmol) of the 0.5M of 4-p-methoxy-phenyl magnesium bromide in the diethyl ether solution (120 μ L) of phenyl aldehyde (77mg, 0.119mmol), at room temperature stirred 13 hours.In reaction solution, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer drying (anhydrous magnesium sulfate), with the solvent concentrating under reduced pressure.With the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 3)) make with extra care, obtain title compound (66mg, 74%).

¹H-NMR(CDCl ₃)δ：1.60-1.80(2H，m)、1.95-2.09(1H，m)、2.66(1H，d，J＝4.78Hz)、3.38-3.79(5H，m)、3.65(1.2H，s)、3.69(1.8H，s)、4.33-4.93(9H，m)、5.96-6.16(1H，m)、6.73-7.42(28H，m)

MS(ESI ⁺)：773[M+Na] ⁺

5) [2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In [2-(2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranosyl)]-(4-p-methoxy-phenyl) methyl alcohol (66mg, 0.0879mmol), add the methanol hydrochloride solution (2mL) of 20% palladium hydroxide carbon (10mg), in nitrogen atmosphere, stirred 3 hours.After the reaction,, filtrate decompression is concentrated reacting liquid filtering, with the residue that obtains with preparing TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (20mg, 61%).

¹H-NMR(CD ₃OD)δ：0.89-1.03(1H，m)、1.40-1.60(1H，m)、2.02-2.10(1H，m)、3.18-3.34(2H，m)、3.45-3.51(2H，m)、3.67-3.71(1H，m)、3.73(3H，s)、3.82-3.99(2H，m)、4.13-4.22(1H，m)、6.78(2H，d，J＝8.57Hz)、6.80-6.86(1H，m)、6.99-7.16(5H，m)

MS(ESI ⁺)：397[M+Na] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 2

[1S, 2R, 3R, 4R, 6S]-4-methylol-6-[3-(4-methoxy-benzyl) phenyl] hexanaphthene-1,2, the 3-triol

1) [2R, 3S, 4R, 5R]-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-methoxy-benzyl) phenyl] hexalin synthetic

Under-78 ℃, in THF (0.80mL) solution of 3-(4-methoxy-benzyl)-1-bromobenzene (155mg, 0.559mmol), drip the 2.44M hexane solution (0.23mL, 0.559mmol) of n-Butyl Lithium, stirred 25 minutes.Then, drip 2,3, THF (0.70mL) solution of 4-three benzyloxies-5-(benzyloxymethyl) pimelinketone (200mg, 0.373mmol) stirred 75 minutes.Add saturated aqueous ammonium chloride, use ethyl acetate extraction, after the water washing of organic layer usefulness saturated common salt, use anhydrous magnesium sulfate drying.Solvent is concentrated, the residue that obtains is made with extra care with silica gel column chromatography (developping solution=ethyl acetate-normal hexane (2: 5)), obtain title compound (80mg, 27%) as the mixture of 1R-body and 1S-body.

¹H-NMR(CDCl ₃)δ：1.82-1.92(1H，m)、2.39-2.44(1H，m)、2.56-2.64(1H，m)、3.34-3.39(1H，m)、3.55-3.80(2H，m)、3.66(3H，s)、3.78(2H，s)、3.87-3.94(2H，m)、4.42-5.04(8H，m)、6.61-6.84(4H，m)、7.06-7.40(23H，m)、7.55-7.66(1H，m)

2) acetate [2R, 3S, 4R, 5R]-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-methoxy-benzyl) phenyl] cyclohexyl synthetic

Under ice-cold, to [2R, 3S, 4R, 5R]-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-methoxy-benzyl) phenyl] add diacetyl oxide (0.003mL) in methylene dichloride (0.10mL) solution of hexalin (20mg), triethylamine (0.008mL) and 4-Dimethylamino pyridine (0.7mg), at room temperature stirred 2 hours.Then, at the ice-cold Acetyl Chloride 98Min. (0.003mL) that adds down, at room temperature stirred 30 minutes.Add saturated sodium bicarbonate aqueous solution, use dichloromethane extraction, the organic layer anhydrous magnesium sulfate drying.Solvent is concentrated, with the residue that obtains with preparing TLC (developping solution=ethyl acetate: normal hexane (2: 5)) make with extra care, obtain title compound (4.2mg).

¹H-NMR(CDCl ₃)δ：1.85(3H，s)、2.03-2.17(2H，s)、3.20-3.49(3H，m)、3.60-3.72(2H，m)、3.67(3H，s)、3.87(2H，s)、4.07(1H，d，J＝9.9Hz)、4.39-4.95(8H，m)、6.72(2H，d，J＝8.6Hz)、6.99-7.40(24H，m)、7.54(1H，d，J＝7.8Hz)、7.65(1H，s)

MS(ESI ⁺)：794[M+H ₂O] ⁺

3) [1S, 2R, 3R, 4R, 6S]-4-methylol-6-[3-(4-methoxy-benzyl) phenyl] hexanaphthene-1,2,3-triol synthetic

To acetate [2R, 3S, 4R, 5R]-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-methoxy-benzyl) phenyl] in methyl alcohol (0.2mL)-THF (0.2mL) solution of cyclohexyl ester (4.2mg), add 20% palladium hydroxide-carbon (3mg), in nitrogen atmosphere, stirred 3 hours.With reacting liquid filtering, filtrate is concentrated, with the residue that obtains with preparing TLC (developping solution=methylene dichloride: methyl alcohol (9: 1)) make with extra care, obtain title compound (1.7mg) as single diastereomer.

¹H-NMR(DMSO-d ₆)δ：1.24(1H，dd，J＝12.9Hz，12.6Hz)、1.48(1H，m)、1.65(1H，dt，J＝13.8Hz，3.3Hz)、2.43(1H，dt，J＝10.4Hz，4.2Hz)、3.05-3.17(2H，m)、3.26-3.40(2H，m)、3.60(1H，m)、3.71(3H，s)、3.83(2H，s)、4.15(1H，d，J＝4.8Hz)、4.21(1H，t，J＝5.1Hz)、4.45(1H，br)、4.60(1H，br)、6.84(2H，m)、6.93-7.08(3H，m)、7.10-7.20(3H，m)

MS(ESI ⁺)：376[M+H ₂O] ⁺

Embodiment 3

[2-(4-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-Trifluoromethoxyphen-l) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 8.7mL), stirred 15 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 3.3g, THF solution (126mL) 12.64mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-trifluoro-methoxybenzaldehyde (2.0g, THF solution (42mL) 10.52mmol).Under uniform temp, stir 40 minutes, again 0 ℃ stir 45 minutes down after, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain the title compound (3.03g, 77%) of colorless oil.

¹H-NMR(CDCl ₃)δ：2.98(1H，d，J＝5.8Hz)、5.01(2H，s)、6.02(1H，d，J＝5.6Hz)、6.84-7.00(2H，m)、7.03-7.37(11H，m)

2) 2-(4-trifluoro-methoxybenzyl) phenol is synthetic

In the methanol solution (27mL) of (2-benzyloxy phenyl)-(4-Trifluoromethoxyphen-l) methyl alcohol (1.5g, 4.01mmol), add 20% palladium hydroxide catalyzer (150mg), add 36%HCl (0.33mL) again.In nitrogen atmosphere, stir after 16 hours, be cooled to 0 ℃, add salt of wormwood (0.54g), stir after 30 minutes, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain the title compound (1.05g, 97%) of white solid.

¹H-NMR(CDCl ₃)δ：3.98(2H，s)、4.83(1H，s)、6.77(1H，d，J＝7.7Hz)、6.89(1H，t，J＝7.3Hz)、6.99-7.13(4H，m)、7.23(2H，d，J＝8.1Hz)

3) [2-(4-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-trifluoro-methoxybenzyl) phenol (298mg, 1.11mmol) toluene solution (2.5mL) in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (400mg, 0.74mmol) and the tributylphosphine (0.28mL, 1.11mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 191mg, 1.11mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stir a night.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)), again with preparing TLC (developping solution=ethyl acetate: normal hexane (1: 5)) handle.The crude product that obtains is dissolved in tetrahydrofuran (THF) (1.4mL), the methyl alcohol (2.8mL), adds 20% palladium hydroxide catalyzer (20mg), in nitrogen atmosphere, stir after 1 hour 45 minutes, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (67mg, 21%).

¹H-NMR(CD ₃OD)δ：0.85-0.99(1H，m)、1.44-1.61(1H，m)、2.00-2.11(1H，m)、3.12-3.33(2H，m)、3.38-3.48(2H，m)、3.64-3.73(1H，m)、3.93(1H，d，J＝14.8Hz)、4.07(1H，d，J＝14.8Hz)、4.12-4.23(1H，m)、6.86(1H，t，J＝7.3Hz)、6.96-7.17(5H，m)、7.29(2H，d，J＝8.6Hz)

MS(ESI ⁺)：428[M] ⁺

The HPLC hold-time: 12.7 minutes

Embodiment 4

[2-(4-cyclopentyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-bromophenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 11.57mL), stirred 15 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 4.4g, THF solution (168mL) 16.72mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-bromobenzaldehyde (2.47g, THF solution (50mL) 13.34mmol).Under uniform temp, stir 30 minutes, again 0 ℃ stir 30 minutes down after, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain the title compound (4.08g, 83%) of colorless oil.

¹H-NMR(CDCl ₃)δ：2.96(1H，d，J＝6.1Hz)、5.01(2H，s)、5.97(1H，d，J＝5.9Hz)、6.86-6.99(2H，m)、7.09-7.39(11H，m)

2) 1-benzyloxy-2-(4-bromobenzyl) benzene is synthetic

In nitrogen gas stream, under-40 ℃, to (2-benzyloxy phenyl)-(4-bromophenyl) methyl alcohol (3.88g, 10.5mmol) acetonitrile solution (19.5mL) in add triethyl silicane (1.84mL, 11.55mmol) and boron trifluoride diethyl etherate coordination compound (1.33mL, 10.5mmol), under uniform temp, stirred 0.5 hour.Add the unsaturated carbonate aqueous solutions of potassium, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (2.86g, 77%).

¹H-NMR(CDCl ₃)δ：3.95(2H，s)、5.03(2H，s)、6.81-6.92(2H，m)、6.96-7.36(11H，m)

3) 1-[4-(2-benzyloxy benzyl) phenyl] cyclopentanol synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 2.94mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 1.5g, THF solution (16.5mL) 4.25mmol) to 1-benzyloxy-2-(4-bromobenzyl) benzene.Under-78 ℃, in this solution, drip cyclopentanone (357mg, THF solution (4mL) 4.25mmol).Under uniform temp, stir 50 minutes, again 0 ℃ stir 1 hour down after, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain the title compound (1.14g, 75%) of colorless oil.

¹H-NMR(CDCl ₃)δ：1.47-2.02(8H，m)、4.00(2H，s)、5.03(2H，s)、6.79-6.89(2H，m)、7.02-7.36(11H，m)

4) 2-(4-cyclopentyl benzyl) phenol is synthetic

To 1-[4-(2-benzyloxy benzyl) phenyl] add 20% palladium hydroxide catalyzer (114mg) in the methanol solution (21mL) of cyclopentanol (1.14g, 3.19mmol), add 36%HCl (0.255mL) again.After in nitrogen atmosphere, stirring a night, be cooled to 0 ℃, add salt of wormwood (425mg), stir after 20 minutes, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 20)) make with extra care, obtain the title compound (744mg, 92%) of white solid.

¹H-NMR(CDCl ₃)δ：1.44-1.84(6H，m)、1.93-2.09(2H，m)、2.84-3.00(1H，m)、3.95(2H，s)、4.76(1H，s)、6.76?(1H，d，J＝8.1Hz)、6.87(1H，t，J＝7.3Hz)、7.02-7.20(6H，m)

5) [2-(4-cyclopentyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-cyclopentyl benzyl) phenol (351mg, 1.39mmo add 2 in toluene solution l) (3.1mL), 3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stir a night.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=normal hexane: methylene dichloride: acetone (12: 3: 1)) handle, obtain crude product (555mg).The crude product (100mg) that obtains is dissolved in tetrahydrofuran (THF) (0.9mL), the methyl alcohol (1.8mL), adds 20% palladium hydroxide catalyzer (12.6mg), in nitrogen atmosphere, stir after 7 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (40mg, 58%).

¹H-NMR(CD ₃OD)δ：0.79-0.96(1H，m)、1.44-1.86(7H，m)、1.93-2.07(3H，m)、2.84-2.99(1H，m)、3.12-3.31(2H，m)、3.37-3.48(2H，m)、3.62-3.71(1H，m)、3.86(1H，d，J＝14.8Hz)、3.98(1H，d，J＝14.8Hz)、4.08-4.20(1H，m)、6.83(1H，t，J＝7.3Hz)、6.93-7.14(7H，m)

MS(ESI ⁺)：413[M+H] ⁺

The HPLC hold-time: 14.5 minutes

Embodiment 5

[2-(4-benzyl chloride base) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-chloro-phenyl-) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 10.3mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 6.0g, THF solution (228mL) 22.8mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-chlorobenzaldehyde (2.67g, THF solution (76mL) 19.0mmol).Under uniform temp, stir after 2 hours, stirred 1 hour down at 0 ℃ again, add entry then, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (4.76g, 77%).

¹H-NMR(CDCl ₃)δ：2.94(1H，s)、5.01(2H，s)、5.99(1H，s)、6.92-7.00(22H，m)、7.17-7.41(11H，m)

2) 1-benzyloxy-2-(4-benzyl chloride base) benzene is synthetic

In nitrogen gas stream, under-40 ℃, to (2-benzyloxy phenyl)-(4-chloro-phenyl-) methyl alcohol (4.76g, 14.6mmol) acetonitrile solution (150mL) in add triethyl silicane (2.8mL, 17.6mmol) and boron trifluoride diethyl etherate coordination compound (1.84mL, 14.6mmol), under uniform temp, stirred 2 hours.After stirring 1 hour under 0 ℃, add entry again, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (3.83g, 85%).

¹H-NMR(CDCl ₃)δ：3.97(2H，s)、5.03(2H，s)、6.87-6.92(2H，m)、7.08-7.37(11H，m)

3) 2-(4-benzyl chloride base) phenol is synthetic

In nitrogen gas stream, under ice-cold, (add dimethyl thioether (105.1 μ L among the 50.0mg, dichloromethane solution 0.16mmol) (2.0mL) to 1-benzyloxy-2-(4-benzyl chloride base) benzene, 2.43mmol) and the boron trifluoride diethyl etherate coordination compound (51.3 μ L, 0.4mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 19 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (33.4mg, 94%).

¹H-NMR(CDCl ₃)δ：3.95(2H，s)、4.60(1H，s)、6.75-6.78(1H，m)、6.86-6.92(1H，m)、7.07-7.27(6H，m)

4) [2-(4-benzyl chloride base) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-benzyl chloride base) phenol (304.5mg, 1.39mmol) toluene solution (2mL) in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the methylene dichloride (8mL), ice-cold add down dimethyl thioether (2.17mL, 50.2mmol) and the boron trifluoride diethyl etherate coordination compound (1.08mL, 8.51mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 25 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (122.6mg, 35%).

¹H-NMR(CD ₃OD)δ：0.95(1H，dd，J＝13.2，11.1Hz)、1.53(1H，m)、2.00-2.09(1H，m)、3.20(1H，d，J＝8.7Hz)、3.25(1H，d，J＝5.1Hz)、3.43-3.51(2H，m)、3.68-3.71(1H，dd，J＝3.9，3.9Hz)、3.91(1H，d，J＝14.7Hz)、3.99(1H，d，J＝15Hz)、4.15-4.23(1H，m)、6.85(1H，t，J＝7.5Hz)、7.03(1H，d，J＝9.0Hz)、7.08-7.23(6H，m)

MS(ESI ⁺)：379[M+H] ⁺

The HPLC hold-time: 11.7 minutes

Embodiment 6

(2-benzyl phenyl)-5a-carbon-β-D-glucopyranoside

1) the 2-benzylphenol is synthetic

In the methanol solution (20mL) of 2-(4-benzyl chloride base) phenol (618.5mg, 2.83mmol), add 20% palladium hydroxide catalyzer (240mg).In nitrogen atmosphere, stir after 3 days, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (348.4mg, 67%).

¹H-NMR(CDCl ₃)δ：3.99(2H，s)、4.65(1H，s)、6.79(1H，d，J＝8.1Hz)、6.89(1H，t，J＝7.5Hz)、7.09-7.31(6H，m)

2) (2-benzyl phenyl)-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 2-benzylphenol (256.5mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 21 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (14mL) of methyl alcohol-THF (1: 1), adds 20% palladium hydroxide catalyzer (118.8mg), in nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (84mg, 26%).

¹H-NMR(CD ₃OD)δ：0.95(1H，dd，J＝12.0，11.7Hz)、1.49-1.59(1H，m)、2.03-2.09(1H，m)、3.20(1H，d，J＝9.0Hz)、3.25(1H，d，J＝5.7Hz)、3.34(4H，s)、3.44-3.50(2H，m)、3.68(1H，dd，J＝3.9，4.2Hz)、3.94(1H，d，J＝15Hz)、4.0(1H，d，J＝15Hz)、4.13-4.22(1H，m)、6.84(1H，t，J＝6.3Hz)、7.03(1H，d，J＝6.3Hz)、7.06-7.24(7H，m)

MS(ESI ⁺)：345[M+H] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 7

[2-(4-isopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-isopropyl phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 5.14mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 3.0g, THF solution (114mL) 11.4mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-isopropyl benzene formaldehyde (1.41g, THF solution (38mL) 9.49mmol).Under uniform temp, stir after 1 hour, stirred 1 hour down at 0 ℃ again, add entry then, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.63g, 84%).

¹H-NMR(CDCl ₃)δ：1.26(6H，d，J＝7.8Hz)、2.84-2.94(1H，m)、5.02(2H，s)、6.02(1H，s)、6.90-7.00(2H，m)、7.15-7.34(11H，m)

2) 2-(4-isopropyl benzyl) phenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy phenyl)-(4-isopropyl phenyl) methyl alcohol (2.63g, 7.92mmol), add 20% palladium hydroxide catalyzer (263mg), add 2N-HCl (0.4mL) again.In nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.31g, 73%).

¹H-NMR(CDCl ₃)δ：1.24(6H，d，J＝7.8Hz)、2.82-2.92(1H，m)、3.96(2H，s)、4.67(1H，s)、6.79(1H，d，J＝9.0Hz)、6.88(1H，t，J＝8.4Hz)、7.10-7.15(6H，m)

3) [2-(4-isopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 2-(4-isopropyl benzyl) phenol (315.1mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (14mL) of methyl alcohol-THF (1: 1), adds 20% palladium hydroxide catalyzer (127.8mg), in nitrogen atmosphere, stir after 17 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (97.1mg, 27%).

¹H-NMR(CD ₃OD)δ：0.94(1H，dd，J＝12.9，12.0Hz)、1.22(6H，d，J＝6.9Hz)、1.48-1.58(1H，m)、2.02-2.09(1H，dt，J＝3.9，4.2Hz)、2.78-2.87(1H，m)、3.12-3.24(2H，m)、3.43-3.49(2H，m)、3.68(1H，dd，J＝6.6，4.2Hz)、3.89(1H，d，J＝14.4Hz)、4.01(1H，d，J＝14.7Hz)、4.13-4.21(1H，m)、6.84(1H，t，J＝6.3Hz)、7.02(1H，d，J＝6.3Hz)、7.06-7.15(6H，m)

MS(ESI ⁺)：387[M+H] ⁺

The HPLC hold-time: 13.1 minutes

Embodiment 8

[2-(4-cyclopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) synthesizing of (2-benzyloxy phenyl)-(4-cyclopropyl phenyl) methyl alcohol

In nitrogen gas stream, under-78 ℃, ((2.6M 3.5mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.2g, THF solution (83mL) 8.3mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-cyclopropyl-phenyl formaldehyde (1.1g, THF solution (28mL) 6.9mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.7g, 75%).

¹H-NMR(CDCl ₃)δ：0.65-0.69(2H，m)、0.92-0.97(2H，m)、1.86-1.90(1H，m)、2.88(1H，d，J＝6Hz)、5.03(2H，s)、6.03(1H，d，J＝6Hz)、7.17-7.26(5H，m)、7.32-7.35(4H，m)

MS(ESI ⁺)：315[M+Na] ⁺

2) 1-benzyloxy-2-(4-cyclopropyl benzyl) benzene is synthetic

In nitrogen gas stream, under-40 ℃, to (2-benzyloxy phenyl)-(4-cyclopropyl phenyl) methyl alcohol (1.3g, 4.0mmol) acetonitrile solution (7mL) in add triethyl silicane (0.73mL, 4.6mmol) and boron trifluoride diethyl etherate coordination compound (0.5mL, 4.0mmol), under uniform temp, stirred 1.5 hours.After stirring 30 minutes under 0 ℃, add entry again, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 7)) make with extra care, obtain title compound (1.2g, 95%).

¹H-NMR(CDCl ₃)δ：0.63-0.67(2H，m)、0.89-0.94(2H，m)、1.84-1.87(1H，m)、3.98(2H，s)、5.06(2H，s)、6.87-6.97(4H，m)、7.08-7.26(4H，m)、7.31-7.37(5H，m)

MS(ESI ⁺)：332[M+H ₂O] ⁺

3) 2-(4-cyclopropyl benzyl) phenol is synthetic

In nitrogen gas stream, under ice-cold, (add dimethyl thioether (2.2mL among the 1.1g, dichloromethane solution 3.5mmol) (24mL) to 1-benzyloxy-2-(4-cyclopropyl benzyl) benzene, 51.7mmol) and the boron trifluoride diethyl etherate coordination compound (1.1mL, 8.8mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 23 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (620.7mg, 79%).

¹H-NMR(CDCl ₃)δ：0.65-0.67(2H，m)、0.90-0.94(2H，m)、1.85-1.86(1H，m)、3.95(2H，s)、4.90(1H，s)、6.79(1H，d，J＝8.1Hz)、6.88(1H，t，J＝7.7Hz)、7.11(2H，d，J＝8.1Hz)、7.20(4H，d，J＝7.7Hz)

MS(ESI ⁺)：247[M+Na] ⁺

4) [2-(4-cyclopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-cyclopropyl benzyl) phenol (348mg, 1.55mmol) toluene solution (3.5mL) in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (557mg, 1.03mmol) and the tributylphosphine (0.37mL, 1.55mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 267mg, 1.55mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 15 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the methylene dichloride (3.5mL), ice-cold add down dimethyl thioether (1.3mL, 30.3mmol) and the boron trifluoride diethyl etherate coordination compound (0.65mL, 5.1mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 14 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (9: 1)) make with extra care, use acetone recrystallization, obtain title compound (97.8mg, 25%).

¹H-NMR(CD ₃OD)δ：0.57-0.61(2H，m)、0.81-0.95(3H，m)、1.50(1H，s)、1.79-1.85(1H，m)、1.99-2.03(1H，m)、3.15-3.33(2H，m)、3.42-3.48(2H，m)、3.66-3.72(1H，m)、3.81-3.99(2H，q，J＝14.7Hz)、4.41-4.85(1H，m)、6.80-7.15(8H，m)

MS(ESI ⁺)：407[M+Na] ⁺

The HPLC hold-time: 12.3 minutes

Embodiment 9

2-(4-n-propyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-n-propyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

(the 4-cyclopropyl benzyl) benzene of synthetic 1-benzyloxy-2-among the embodiment 8 (640.8mg, 2.0mmol) is dissolved in 2, in the 2-dimethyl propyl alcohol (12mL), add 20% palladium hydroxide catalyzer (64mg), in nitrogen atmosphere, stir after 2 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) handle.In nitrogen gas stream, under ice-cold, in the toluene solution (3.5mL) of the crude product that obtains (348mg), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (557mg, 1.03mmol) and the tributylphosphine (0.39mL, 1.55mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 267mg, 1.55mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) handle.The crude product that obtains is dissolved in 2,2-dimethyl propyl alcohol (15mL), adds 20% palladium hydroxide catalyzer (159mg), in nitrogen atmosphere, stir after 17 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (9: 1)) make with extra care, obtain title compound (164.4mg).

¹H-NMR(CD ₃OD)δ：0.88-0.94(4H，m)、1.48-1.63(3H，m)、2.05-2.09(1H，m)、2.52(2H，t，J＝7.7Hz)、3.13-3.30(2H，m)、3.46(2H，m)、3.70(1H，m)、3.87(1H，d，J＝15Hz)、3.98(1H，d，J＝15Hz)、4.60-4.88(1H，m)、6.84(1H，t，J＝7.3Hz)、7.00-7.16(7H，m)

MS(ESI ⁺)：387[M+H] ⁺

The HPLC hold-time: 13.3 minutes

Embodiment 10

[2-(4-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-trifluoromethyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 4.0mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.6g, THF solution (100mL) 9.9mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, and dropping 4-trifluoromethylated benzaldehyde in this solution (1.6g, 9.0mmol).Under uniform temp, stir after 2 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.6g, 82%).

¹H-NMR(CDCl ₃)δ：3.01(1H，d，J＝6.3Hz)、5.02(2H，dd，J＝11.4，4.8Hz)、6.05(1H，d，J＝6.3Hz)、6.94-7.02(2H，m)、6.96-7.16(2H，m)、7.24-7.33(5H，m)、7.44(2H，d，J＝7.1Hz)、7.53(2H，d，J＝8.7Hz)

MS(ESI ⁺)：359[M+H] ⁺

2) 2-(4-trifluoromethyl benzyl) phenol is synthetic

In the methanol solution (68.5mL) of (2-benzyloxy phenyl)-(4-trifluoromethyl) methyl alcohol (2.46g, 6.85mmol), add 20% palladium hydroxide catalyzer (246mg), add 36%HCl (0.59mL) again.In nitrogen atmosphere, stir after 3.5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 8)) make with extra care, obtain title compound (1.49g, 86%).

¹H-NMR(CDCl ₃)δ：4.03(2H，s)、4.72(1H，s)、6.77(1H，d，J＝6.0Hz)、6.89(1H，t，J＝4.8Hz)、7.08-7.15(2H，m)、7.33(2H，d，J＝6.0Hz)、7.52(2H，d，J＝6.0Hz)

MS(ESI ⁺)：275[M+Na] ⁺

3) [2-(4-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-trifluoromethyl benzyl) phenol (351mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (5mL) of methyl alcohol-THF (1: 1), adds 20% palladium hydroxide catalyzer (20mg), in nitrogen atmosphere, stir after 2 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (74mg, 19%).

¹H-NMR(CD ₃OD)δ：0.89(1H，dd，J＝11.7，12.9Hz)、1.48-1.61(1H，m)、2.05(1H，dt，J＝13.2，4.2Hz)、3.15-3.34(2H，m)、3.42-3.49(2H，m)、3.69(1H，dd，J＝3.9，10.5Hz)、3.96-4.15(2H，dd，J＝14.7，28.2Hz)、4.17-4.24(1H，m)、6.87(1H，dt，J＝1.2，7.5Hz)、7.02-7.20(3H，m)、7.38(2H，d，J＝8.1Hz)、7.51(2H，d，J＝8.4Hz)

MS(ESI ⁺)：435[M+Na] ⁺

The HPLC hold-time: 12.3 minutes

Embodiment 11

[2-(4-methyl sulfane base benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) synthesizing of (2-benzyloxy phenyl)-(4-methyl sulfane base phenyl) methyl alcohol

In nitrogen gas stream, under-78 ℃, ((1.59M 6.92mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.89g, THF solution (38mL) 11.0mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-methyl sulfane benzaldehyde (1.67g, THF solution (12mL) 11.0mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.14g, 58%).

¹H-NMR(CDCl ₃)δ：2.47(3H，s)、2.92(1H，d，J＝6.0Hz)、5.03(2H，s)、6.02(1H，d，J＝6.0Hz)、6.92-7.00(2H，m)、7.21-7.34(11H，m)

2) 1-benzyloxy-2-(4-methyl sulfane base benzyl) benzene is synthetic

In nitrogen gas stream, under-40 ℃, to (2-benzyloxy phenyl)-(4-methyl sulfane base phenyl) methyl alcohol (2.13g, 6.3mmol) acetonitrile solution (15mL) in add triethyl silicane (1.23mL, 7.72mmol) and boron trifluoride diethyl etherate coordination compound (0.88mL, 5.48mmol), under uniform temp, stirred 1.5 hours.After stirring 30 minutes under 0 ℃, add entry again, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (1.9g, 95%).

¹H-NMR(CDCl ₃)δ：2.46(3H，s)、3.97(2H，s)、5.05(2H，s)、6.85-6.95(2H，m)、7.10-7.35(11H，m)

3) 2-(4-methyl sulfane base benzyl) phenol is synthetic

In nitrogen gas stream, under ice-cold, (add dimethyl thioether (7.25mL among the 1.9g, dichloromethane solution 5.9mmol) (15mL) to 1-benzyloxy-2-(4-methyl sulfane base benzyl) benzene, 138mmol) and the boron trifluoride diethyl etherate coordination compound (2.1mL, 13mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 48 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.19g, 91%).

¹H-NMR(CDCl ₃)δ：2.46(3H，s)、3.95(2H，s)、4.65-4.75(1H，br?s)、6.78(1H，d，J＝7.6Hz)、6.89(1H，t，J＝7.6Hz)、7.09-7.21(6H，m)

4) [2-(4-methyl sulfane base benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-methyl sulfane base benzyl) phenol (320mg, 1.39mmol) toluene solution (2mL) in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the methylene dichloride (10mL), ice-cold add down dimethyl thioether (3.28mL, 63mmol) and the boron trifluoride diethyl etherate coordination compound (0.94mL, 5.9mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 20 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (102mg, 28%).

¹H-NMR(CD ₃OD)δ：0.80-0.95(1H，m)、1.45-1.60(1H，m)、2.00-2.10(1H，m)、2.42(3H，s)、3.12-3.33(2H，m)、3.40-3.50(2H，m)、3.63-3.70(1H，m)、3.86(1H，d，J＝15Hz)、4.00(1H，d，J＝15Hz)、4.15-4.23(1H，m)、6.84(1H，t，J＝7.0Hz)、7.00-7.18(7H，m)

MS(ESI ⁺)：391[M+H] ⁺

The HPLC hold-time: 11.6 minutes

Embodiment 12

[3-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy-6-fluorophenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, at room temperature, in the THF solution (50mL) of 2-benzyloxy-6-fluorobenzaldehyde (2.25g, 9.8mmol) of in the open WO04/048335 in the world, putting down in writing, drip the THF solution (0.5M, 21.5mL) of 4-p-methoxy-phenyl magnesium bromide.After at room temperature stirring 1.5 hours,, use ethyl acetate extraction at the ice-cold saturated aqueous ammonium chloride that adds down.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.82g, 85%).

¹H-NMR(CDCl ₃)δ：3.78(1H，d，J＝12Hz)、3.80(3H，s)、4.98(1H，d，J＝12Hz)、5.05(1H，d，J＝12Hz)、6.20(1H，d，J＝12Hz)、6.74-6.84(4H，m)、7.11-7.31(8H，m)

2) 3-fluoro-2-(4-methoxy-benzyl) phenol is synthetic

To 2-benzyloxy-6-fluorophenyl)-add 20% palladium hydroxide catalyzer (381mg) in the methanol solution (20mL) of (4-p-methoxy-phenyl) methyl alcohol (2.54g, 7.51mmol), add 2N-HCl (2mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.48g, 85%).

¹H-NMR(CDCl ₃)δ：3.76(3H，s)、3.96(2H，s)、4.90(1H，br?s)、6.57(1H，d，J＝8.0Hz)、6.67(1H，t，J＝8.0Hz)、6.82(2H，d，J＝9.0Hz)、7.06(1H，dd，J＝8.0，8.0Hz)、7.19(2H，d，J＝9.0Hz)

3) [3-fluoro-2-(4-methoxy-benzyl)-phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 3-fluoro-2-(4-methoxy-benzyl) phenol (323mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (5mL) of methyl alcohol-THF (1: 4), adds 20% palladium hydroxide catalyzer (63mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (86mg, 24%).

¹H-NMR(CD ₃OD)δ：0.90-1.05(1H，m)、1.45-1.60(1H，m)、2.00-2.10(1H，m)、3.17-3.35(2H，m)、3.45-3.52(2H，m)、3.65-3.70(1H，m)、3.72(3H，s)、3.93(2H，s)、4.15-4.25(1H，m)、6.67(1H，t，J＝8.0Hz)、6.76(2H，d，J＝9.0Hz)、6.86(1H，d，J＝8.0Hz)、7.09-7.18(3H，m)

MS(ESI ^-)：391[M-H] ^-

The HPLC hold-time: 10.8 minutes

Embodiment 13

[2-(3-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(3-trifluoromethyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.7M 3.4mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.0g, THF solution (50mL) 7.6mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, and dropping 4-trifluoromethylated benzaldehyde in this solution (2.0g, 11.4mmol).Under uniform temp, stir after 3 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (2.2g, 80%).

¹H-NMR(CDCl ₃)δ：3.03(1H，d，J＝6.3Hz)、4.97-5.07(2H，m)、6.06(1H，d，J＝6.3Hz)、6.95-7.03(2H，m)、7.16-7.20?(2H，m)、7.26(1H，dd，J＝7.7，2.0Hz)、7.29-7.36(4H，m)、7.39(1H，d，J＝7.7Hz)、7.46-7.55(2H，m)、7.67(1H，s)

2) 2-(3-trifluoromethyl benzyl) phenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy phenyl)-(3-trifluoromethyl) methyl alcohol (3.32g, 9.3mmol), add 20% palladium hydroxide catalyzer (166mg), add 36%HCl (0.2mL) again.In nitrogen atmosphere, stir after 72 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (2.26g, 96%).

¹H-NMR(CDCl ₃)δ：4.04(2H，s)、4.90(1H，d，J＝2.0Hz)、6.76(1H，d，J＝8.1Hz)、6.86-6.90(1H，m)、7.09-7.16(2H，m)、7.34-7.46(3H，m)、7.50(1H，s).

3) [2-(3-trifluoromethyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(3-trifluoromethyl benzyl) phenol (351mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (45mg), in nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (56mg, 14%).

¹H-NMR(CD ₃OD)δ：0.88-1.02(1H，m)、1.52-1.68(1H，m)、2.10(1H，dt，J＝13.4，3.9Hz)、3.20-3.38(2H，m)、3.45-3.55(2H，m)、3.74(1H，dd，J＝4.1，10.8Hz)、3.99(1H，d，J＝14.7Hz)、4.18(1H，d，J＝15.4Hz)、4.20-4.32(1H，m)、6.89-6.95(1H，m)、7.08(1H，d，J＝7.7Hz)、7.16-7.26(2H，?m)、7.42-7.58(4H，m)

MS(ESI ⁺)：413[M+H] ⁺

The HPLC hold-time: 12.0 minutes

Embodiment 14

[2-(4-methoxy-benzyl)-4-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside

1) 1-benzyloxy-2-bromo-4-methylbenzene is synthetic

To the N of 2-bromo-4-methylphenol (1.5g, 8.0mmol), add salt of wormwood (1.32g, 9.6mmol) in the dinethylformamide solution (40mL), add bromotoluene (1.05mL, 8.8mmol) again.After at room temperature stirring 12 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.72g, 77%).

¹H-NMR(CDCl ₃)δ：2.30(3H，s)、5.12(2H，s)、6.82(1H，d，J＝8.4Hz)、6.99-7.03(1H，m)、7.28-7.41(4H，m)、7.45-7.48(2H，m)

2) (2-benzyloxy-5-aminomethyl phenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.7M 2.75mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 1.72g, THF solution (50mL) 6.2mmol) to 1-benzyloxy-2-bromo-4-methylbenzene.Under-78 ℃, and dropping 4-methoxybenzaldehyde in this solution (1.27g, 9.3mmol).Under uniform temp, stir after 2 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.46g, 70%).

¹H-NMR(CDCl ₃)δ：2.28(3H，s)、2.88(1H，d，J＝9.2Hz)、3.80(3H，s)、5.00(2H，s)、5.99(1H，d，J＝5.6Hz)、6.80-6.88(3H，m)、7.00-7.05(1H，m)、7.13(1H，d，J＝1.8Hz)、?7.19-7.34(7H，m)

3) 2-(4-methoxy-benzyl)-4-methylphenol is synthetic

In the methanol solution (20mL) of (2-benzyloxy-5-p-methoxy-phenyl)-(4-p-methoxy-phenyl) methyl alcohol (1.46g, 4.3mmol), add 20% palladium hydroxide catalyzer (73mg), add 36%HCl (0.1mL) again.In nitrogen atmosphere, stir after 72 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (0.8g, 80%).

¹H-NMR(CDCl ₃)δ：2.24(3H，s)、3.77(3H，s)、3.89(2H，s)、4.55-4.56(1H，m)、6.65-6.69(1H，m)、6.80-6.86(2H，m)、6.88-6.94(2H，m)、7.11-7.16(2H，m)

4) [2-(4-methoxy-benzyl)-4-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-methoxy-benzyl)-4-methylphenol (317mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (44mg), in nitrogen atmosphere, stir after 4 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (88mg, 24%).

¹H-NMR(CD ₃OD)δ：0.88-1.02(1H，m)、1.42-1.60(1H，m)、2.04(1H，dt，J＝13.4，4.0Hz)、2.21(3H，s)、3.17-3.32(2H，m)、3.43-3.51(2H，m)、3.70(1H，dd，J＝4.1，10.7Hz)、3.74(3H，s)、3.82(1H，d，J＝14.7Hz)、3.92(1H，d，J＝14.7Hz)、4.06-4.16(1H，m)、6.77-6.82(2H，m)、6.86-6.96(3H，m)、7.06-7.15(2H，m)

MS(ESI ⁺)：389[M+H] ⁺

The HPLC hold-time: 11.2 minutes

Embodiment 15

[2-(3-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(3-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under ice-cold, in the THF solution (50mL) of 2-benzyloxy phenyl aldehyde (3.0g, 14.1mmol), drip the THF solution (1.0M, 17.0mL) of 3-p-methoxy-phenyl magnesium bromide.After at room temperature stirring 1 hour,, use ethyl acetate extraction at the ice-cold saturated aqueous ammonium chloride that adds down.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (4.92g, 100%).

¹H-NMR(CDCl ₃)δ：2.97(1H，dd，J＝1.1，6.0Hz)、3.73(3H，s)、4.98-5.10(2H，m)、6.03(1H，d，J＝6.0Hz)、6.77-6.82(1H，m)、6.88-7.01(4H，m)、7.19-7.35(9H，m)

2) 2-(3-methoxy-benzyl) phenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy phenyl)-(3-p-methoxy-phenyl) methyl alcohol (1.68g, 5.24mmol), add 20% palladium hydroxide catalyzer (168mg), add 36%HCl (0.2mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.29g, 100%).

¹H-NMR(CDCl ₃)δ：3.76(3H，s)、3.97(2H，s)、4.69(1H，s)、6.73-6.92(5H，m)、7.10-7.23(3H，m)

3) [2-(3-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(3-methoxy-benzyl) phenol (298mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (55mg), in nitrogen atmosphere, stir after 4 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (111mg, 32%).

¹H-NMR(CD ₃OD)δ：0.97-1.11(1H，m)、1.52-1.68(1H，m)、2.12(1H，dt，J＝13.4，4.0Hz)、3.22-3.39(2H，m)、3.49-3.56(2H，m)、3.72-3.78(1H，m)、3.78(3H，s)、3.92(1H，d，J＝14.8Hz)、4.05(1H，d，J＝14.8Hz)、4.18-4.27(1H，m)、6.72-6.92(4H，m)、7.05-7.22(4H，m)

MS(ESI ⁺)：375[M+H] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 16

[2-(4-methoxy-benzyl)-4-p-methoxy-phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-benzyloxy-5-methoxybenzaldehyde is synthetic

To the N of 2-hydroxy-5-methyl oxygen benzaldehyde (3.0g, 19.7mmol), add salt of wormwood (3.27g, 23.6mmol) in the dinethylformamide solution (50mL), add bromotoluene (2.6mL, 21.7mmol) again.After at room temperature stirring 24 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (4.8g, 100%).

¹H-NMR(CDCl ₃)δ：3.80(3H，s)、5.15(2H，s)、6.99(1H，d，J＝9.0Hz)、7.11(1H，dd、J＝3.4，9.1Hz)、7.32-7.44(6H，m)、10.50(1H，s)

2) (2-benzyloxy-5-p-methoxy-phenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under ice-cold, in the THF solution (50mL) of 2-benzyloxy-5-methoxybenzaldehyde (2.0g, 8.25mmol), drip the THF solution (0.5M, 19.8mL) of 4-p-methoxy-phenyl magnesium bromide.After at room temperature stirring 1 hour,, use ethyl acetate extraction at the ice-cold saturated aqueous ammonium chloride that adds down.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 1)) make with extra care, obtain title compound (2.9g, 100%).

¹H-NMR(CDCl ₃)δ：2.85(1H，d，J＝5.4Hz)、3.76(3H，s)、3.79(3H，s)、4.96(2H，s)、5.99(1H，d，J＝5.4Hz)、6.74(1H，dd，J＝2.8，9.0Hz)、6.81-6.87(3H，m)、6.94(1H，d，J＝4.1Hz)、7.19-7.36(7H，m)

3) 2-(4-methoxy-benzyl)-4-methoxyphenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy-5-p-methoxy-phenyl)-(4-p-methoxy-phenyl) methyl alcohol (2.54g, 7.25mmol), add 20% palladium hydroxide catalyzer (250mg), add 36%HCl (0.25mL) again.In nitrogen atmosphere, stir after 14 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.62g, 91%).

¹H-NMR(CDCl ₃)δ：3.74(3H，s)、3.78(3H，s)、3.90(2H，s)、4.41(1H，br?s)、6.64-6.86(5H，m)、7.11-7.16(2H，m)

4) [2-(4-methoxy-benzyl)-4-p-methoxy-phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-methoxy-benzyl)-4-methoxyphenol (340mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (40mg), in nitrogen atmosphere, stir after 6 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (128mg, 34%).

¹H-NMR(CD ₃OD)δ：0.94-1.08(1H，m)、1.45-1.62(1H，m)、2.06(1H，dt，J＝13.0，4.0Hz)、3.20-3.34(2H，m)、3.46-3.56(2H，m)、3.70-3.80(1H，m)、3.73(3H，s)、3.79(3H，s)、3.88(1H，d，J＝14.8Hz)、3.96(1H，d，J＝14.8Hz)、4.04-4.14(1H，m)、6.67(1H，d，J＝3.1Hz)、6.74(1H，dd，J＝3.1，8.7Hz)、6.80-6.88(2H，m)、7.00(1H，d，J＝8.7Hz)、7.12-7.18(2H、m)

MS(ESI ⁺)：405[M+H] ⁺

The HPLC hold-time: 10.2 minutes

Embodiment 17

[2-(4-methoxy-benzyl)-6-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-benzyloxy-3-tolyl aldehyde is synthetic

To the N of 2-hydroxy-3-methyl phenyl aldehyde (3.0g, 22.07mmol), add salt of wormwood (3.65g, 26.4mmol) in the dinethylformamide solution (50mL), add bromotoluene (2.9mL, 24.2mmol) again.After at room temperature stirring 26 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (5.0g, 100%).

¹H-NMR(CDCl ₃)δ：2.36(3H，s)、4.97(2H，s)、7.16(1H，t，J＝7.4Hz)、7.36-7.49(6H，m)、7.68(1H，dd，J＝1.4，7.8Hz)、10.26(1H，d，J＝0.5Hz)

2) (2-benzyloxy-3-aminomethyl phenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under ice-cold, in the THF solution (50mL) of 2-benzyloxy-3-tolyl aldehyde (1.87g, 8.25mmol), drip the THF solution (0.5M, 19.8mL) of 4-p-methoxy-phenyl magnesium bromide.After at room temperature stirring 1 hour,, use ethyl acetate extraction at the ice-cold saturated aqueous ammonium chloride that adds down.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.76g, 100%).

¹H-NMR(CDCl ₃)δ：2.36(3H，s)、2.63(1H，d，J＝5.0Hz)、3.78(3H，s)、4.64-4.73(2H，m)、6.02(1H，d，J＝5.0Hz)、6.77-6.86(2H，m)、7.02-7.08(1H，m)、7.15-7.21(2H，m)、7.22-7.28(2H，m)、7.34-7.40(5H，m)

3) 2-(4-methoxy-benzyl)-6-methylphenol is synthetic

In the methanol solution (30mL) of (2-benzyloxy-3-aminomethyl phenyl)-(4-p-methoxy-phenyl) methyl alcohol (2.76g, 8.25mmol), add 20% palladium hydroxide catalyzer (276mg), add concentrated hydrochloric acid (0.27mL) again.In nitrogen atmosphere, stir after 18 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.75g, 93%).

¹H-NMR(CDCl ₃)δ：2.22(3H，s)、3.78(3H，s)、3.93(2H，s)、4.63(1H，br?s)、6.77-6.86(3H，m)、6.96-7.05(2H，m)、7.11-7.17(2H，m)

4) [2-(4-methoxy-benzyl)-6-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-methoxy-benzyl)-6-methylphenol (318mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 48 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (72mg), in nitrogen atmosphere, stir after 4 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (180mg, 50%).

¹H-NMR(CD ₃OD)δ：1.16-1.35(2H，m)、1.74-1.88(1H，m)、2.33(3H，s)、3.16-3.26(2H，m)、3.42-3.52(1H，m)、3.54-3.68(2H，m)、3.74(3H，s)、3.92-4.02(2H，m)、4.08(1H，d，J＝15.3Hz)、6.77-6.83(2H，m)、6.86-6.91(2H，m)、6.96-7.04(1H，m)、7.05-7.12(2H，m)

MS(ESI ⁺)：411[M+Na] ⁺

The HPLC hold-time: 10.8 minutes

Embodiment 18

[2-(4-methoxy-benzyl)-4-fluorophenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy-5-fluorophenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 2.4mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 1.5g, THF solution (60mL) 5.33mmol) to 1-benzyloxy-2-bromo-4-fluorobenzene.Under-78 ℃, in this solution, drip 4-methoxybenzaldehyde (0.6g, THF solution (20mL) 4.42mmol).Under uniform temp, stir after 1 hour, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (0.98g, 66%).

¹H-NMR(CDCl ₃)δ：2.66(1H，dd，J＝0.8，4.9Hz)、3.80(3H，s)、4.98(2H，s)、6.01(1H，d，J＝4.9Hz)、6.83-6.90(4H，m)、7.14(1H，dd，J＝3.0，9.0Hz)、7.20-7.34(7H，m)

2) 4-fluoro-2-(4-methoxy-benzyl) phenol is synthetic

In the methanol solution (18.6mL) of (2-benzyloxy-5-fluorophenyl)-(4-p-methoxy-phenyl) methyl alcohol (0.98g, 2.90mmol), add 20% palladium hydroxide catalyzer (98mg), add 2N-HCl (1mL) again.In nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 6)) make with extra care, obtain title compound (0.55g, 82%).

¹H-NMR(CDCl ₃)δ：3.78(3H，s)、3.89(2H，s)、4.65(1H，br?s)、6.68-6.73(1H，m)、6.77-6.87(4H，m)、7.11-7.12(2H，m)

3) [2-(4-methoxy-benzyl)-4-fluorophenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-methoxy-benzyl)-4-fluorophenol (323mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 48 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (5: 2), adds 20% palladium hydroxide catalyzer (22mg), in nitrogen atmosphere, stir after 4 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (103mg, 29%).

¹H-NMR(CD ₃OD)δ：0.99-1.13(1H，m)、1.50-1.65(1H，m)、2.08(1H，dt，J＝13.4，4.0Hz)、3.22-3.35(2H，m)、3.50-3.57(2H，m)、3.75(1H，dd，J＝4.0，10.7Hz)、3.79(3H，s)、3.87-4.02(2H，m)、4.11-4.21(1H，m)、6.79(1H，dd，J＝3.1，9.4Hz)、6.83-6.92(3H，m)、7.06(1H，dd，J＝4.7，8.9Hz)、7.12-7.20(2H，m)

MS(ESI ⁺)：415[M+Na] ⁺

The HPLC hold-time: 10.9 minutes

Embodiment 19

[2-(3-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(3-fluorophenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 5.65mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 3.3g, THF solution (40mL) 12.5mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 3-fluorobenzaldehyde (1.40g, THF solution (5mL) 11.3mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (2.26g, 65%).

¹H-NMR(CDCl ₃)δ：3.00(1H，d，J＝6.3Hz)、5.57(1H，d，J＝11.5Hz)、5.60(1H，d，J＝11.5Hz)、6.01(1H，d，J＝6.3Hz)、6.85-7.15(5H，m)、7.17-7.4(7H，m)

MS(ESI ⁺)：308[M] ⁺

2) 2-(3-luorobenzyl) phenol is synthetic

In the methanol solution (30mL) of (2-benzyloxy phenyl)-(3-fluorophenyl) methyl alcohol (2.54g, 7.51mmol), add 20% palladium hydroxide catalyzer (300mg), add 2N-HCl (0.3mL) again.In nitrogen atmosphere, stir after 5 days, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (620mg, 42%).

¹H-NMR(CDCl ₃)δ：3.98(2H，s)、4.70(1H，s)、6.75-7.3(8H，m)

MS(ESI ^-)：201[M-H] ^-

3) [2-(3-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

In nitrogen gas stream, under ice-cold, in the toluene solution (2.5mL) of 2-(3-luorobenzyl) phenol (225mg, 1.11mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-β-D-Glucopyranose (400mg, 0.743mmol) and the tributylphosphine (0.278mL, 1.11mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 192mg, 1.11mmol).Descend stirring after 5 hours at 0 ℃ reaction solution, Yi Bian slowly rise to room temperature, Yi Bian stirred 14 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (2: 5), adds 20% palladium hydroxide catalyzer (40mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (76mg, 28%).

¹H-NMR(CD ₃OD)δ：0.99(1H，dd，J＝24.7Hz，13.2Hz)、1.45-1.62(1H，m)、2.09(1H，dt，J＝12.6Hz，4Hz)、3.16-3.3(2H，m)、3.4-3.55(2H，m)、3.71(1H，dd，J＝10.7，3.8Hz)、3.93(1H，d，J＝14.9Hz)、4.05(1H，d，J＝14.9Hz)、4.1-4.3(1H，m)、6.8-6.95(3H，m)、7.0-7.06(2H，m)、7.08-7.27(3H，m).

MS(ESI ⁺)：363[M+H] ⁺、385[M+Na] ⁺

The HPLC hold-time: 10.9 minutes

Embodiment 20

[2-(3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to Uzbekskii Khimicheskii Zhurnal (1984), (6), add 2,3,4 in the toluene solution (2.5mL) of 2-(3-methyl-benzyl) phenol (228mg, 1.15mmol) of record among the 31-4 etc., behind 6-four-O-benzyl-5a-carbon-β-D-Glucopyranose (413mg, 0.743mmol) and the tributylphosphine (0.233mL, 1.15mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 198mg, 1.15mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 15 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (2: 5), adds 20% palladium hydroxide catalyzer (40mg), in nitrogen atmosphere, stir after 6 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (109mg, 40%).

¹H-NMR(CD ₃OD)δ：0.95(1H，dd，J＝24.4Hz，12.9Hz)、1.45?-1.62(1H，m)、2.06(1H，dt，J＝13.1，4.0Hz)、2.27(3H，s)、3.15-3.30(2H，m)、3.42-3.52(2H，m)、3.70(1H，dd，J＝10.7，3.9Hz)、3.87(1H，d，J＝14.8Hz)、3.98(1H，d，J＝14.8Hz)、4.1-4.25(1H，m)、6.81-6.88(1H，m)、6.9-7.2(7H，m)

MS(ESI ⁺)：376[M+NH ₄] ⁺、359[M+H] ⁺

The HPLC hold-time: 11.4 minutes

Embodiment 21

[5-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-benzyloxy-1-bromo-4-fluorobenzene is synthetic

((2.61g 18.8mmol), in nitrogen gas stream, at room temperature stirred 15 minutes to add salt of wormwood among the 3.0g, DMF solution (15.7mL) 15.7mmol) to 2-bromo-5-fluorophenol.Under uniform temp, (2.69g 15.7mmol), stirs a night under uniform temp to drip bromotoluene in this solution.Add aqueous potassium hydrogen sulfate, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.The residue that obtains is made with extra care with silica gel column chromatography (developping solution=normal hexane), obtained the title compound (4.31g, 98%) of colorless oil.

¹H-NMR(CDCl ₃)δ：5.14(2H，s)、6.56-6.72(2H，m)、7.31-7.52(6H，m)

2) (2-benzyloxy-4-fluorophenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 3.14mL), stirred 15 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 1.4g, THF solution (50mL) 5.0mmol) to 2-benzyloxy-1-bromo-4-fluorobenzene.Under-78 ℃, in this solution, drip 4-methoxybenzaldehyde (680mg, THF solution (15mL) 4.99mmol).Under uniform temp, stir after 1.5 hours, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=normal hexane: methylene dichloride: acetone (12: 3: 1)) make with extra care, obtain the title compound (1.41g, 83%) of colorless oil.

¹H-NMR(CDCl ₃)δ：2.67(1H，d，J＝5.0Hz)、3.79(3H，s)、4.99(2H，s)、6.00(1H，d，J＝3.8Hz)、6.62-6.70(2H，m)、6.81-6.86(2H，m)、7.19-7.38(8H，m)

3) 2-(4-methoxy-benzyl)-5-fluorophenol is synthetic

In the methanol solution (20mL) of (2-benzyloxy-4-fluorophenyl)-(4-p-methoxy-phenyl) methyl alcohol (2.095g, 6.19mmol), add 20% palladium hydroxide catalyzer (200mg), add 2N-HCl (0.3mL) again.In nitrogen atmosphere, stir after 16 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (489mg, 34%).

¹H-NMR(CDCl ₃)δ：3.78(3H，s)、3.89(2H，s)、4.88(1H，s)、6.50-6.40(2H，m)、6.80-6.88(2H，m)、7.04(1H，dd，J＝6.6，8.2Hz)、7.08-7.15(2H，m)

MS(ESI ^-)：231[M-H] ^-

4) [5-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon (carba)-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2.5mL) of 2-(4-methoxy-benzyl)-5-fluorophenol (323mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-β-D-Glucopyranose (500mg, 0.928mmol) and the tributylphosphine (0.346mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 240mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 17 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (7mL) of methyl alcohol-THF (2: 5), adds 20% palladium hydroxide catalyzer (40mg), in nitrogen atmosphere, stir after 22 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (59mg, 16%).

¹H-NMR(CD ₃OD)δ：1.00(1H，dd，J＝24.4，12.9Hz)、1.5-1.65(1H，m)、2.04(1H，dt，J＝13.4，4.1Hz)、3.17-3.35(2H，m)、3.43-3.55(2H，m)、3.65-3.75(1H，m)、3.73(3H，s)、3.81(1H，d，J＝15.1Hz)、3.90(1H，d，J＝15.1Hz)、4.1-4.22(1H，m)、6.56(1H，dt，J＝8.5，2.7Hz)、6.75-6.88(3H，m)、7.0-7.13(3H，m)

MS(ESI ⁺)：415[M+Na] ⁺

The HPLC hold-time: 11.0 minutes

Embodiment 22

[2-(4-methyl sulphonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

In nitrogen gas stream, under 0 ℃, in the THF solution (24mL) of 2-benzyloxy phenyl aldehyde (2.60g, 12.2mmol), drip the THF solution (0.5M, 35mL) of 4-methyl sulfane base phenyl-magnesium-bromide.After at room temperature stirring 2 hours,, use ethyl acetate extraction at the ice-cold saturated aqueous ammonium chloride that adds down.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (3.91g, 95%).

¹H-NMR(CDCl ₃)δ：2.47(3H，s)、2.91(1H，d，J＝5.8Hz)、5.03(2H，s)、6.01(1H，d，J＝6.0Hz)、6.90-7.00(2H，m)、7.15-7.35(11H，m)

2) synthesizing of (2-benzyloxy phenyl)-(4-methane sulfonyl phenyl) methyl alcohol

In nitrogen gas stream, under 0 ℃, ((4.40g 22.2mmol), stirred 30 minutes under uniform temp to add metachloroperbenzoic acid among the 3.00g, dichloromethane solution 8.92mmol) (25mL) to (2-benzyloxy phenyl)-(4-methyl sulfane base phenyl) methyl alcohol.After removing by filter throw out, filtrate is washed with the 2N aqueous sodium hydroxide washes.With the washings dichloromethane extraction, with organic layer water and the saturated common salt water washing that merges, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates, and obtains title compound (3.18g, 97%).

¹H-NMR(CDCl ₃)δ：3.02(3H，s)、3.03(1H，d，J＝6.3Hz)、5.00(1H，J＝11.4Hz)、5.04(1H，d，J＝11.5Hz)、6.09(1H，d，J＝6.2Hz)、6.95-7.03(2H，m)、7.16-7.22(2H，m)、7.24-7.38(5H，m)、7.53(2H，d，J＝8.1Hz)、?7.84(2H，d，J＝8.6Hz)

3) 2-(4-methane sulfonyl benzyl) phenol is synthetic

In nitrogen gas stream; to (2-benzyloxy phenyl)-(4-methane sulfonyl phenyl) methyl alcohol (3.00g; 8.14mmol) methyl alcohol (30mL)-ethyl acetate (30mL) mixing solutions in add 20% palladium hydroxide catalyzer (299mg) and 36%HCl (150 μ L; 1.78mmol), in nitrogen atmosphere, stirred 6 hours.Add sodium bicarbonate, stirred 30 minutes, after the neutralization, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 2)) make with extra care, obtain title compound (1.81g, 85%).

¹H-NMR(CDCl ₃)δ：3.02(3H，s)、4.06(2H，s)、5.00(1H，s)、6.77(1H，d，J＝7.9Hz)、6.89(1H，dt，J＝7.5，1.2Hz)、7.08-7.17(2H，m)、7.42(2H，d，J＝8.6Hz)、7.82(2H，d，J＝8.4Hz)

4) [2-(4-methane sulfonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream; under ice-cold; to 2-(4-methane sulfonyl benzyl) phenol (365mg; 1.39mmol) toluene (2mL)-THF (1mL) mixing solutions in add 2; 3; 4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.928mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 242mg, 1.41mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 25 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4 → 1: 2)) handle.The crude product that obtains is dissolved in methyl alcohol (3mL)-THF (2mL) mixed solvent, adds 20% palladium hydroxide catalyzer (27.2mg) and 1 2N hydrochloric acid, in nitrogen atmosphere, stirred 2.5 hours.After the adding saturated sodium bicarbonate aqueous solution neutralizes, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (8: 1)) make with extra care, obtain title compound (120mg, 31%).

¹H-NMR(CD ₃OD)δ：0.91(1H，ddd，J＝13.0，13.0，13.0Hz)、1.53(1H，m)、2.03(1H，ddd，J＝13.0，4.0，4.0Hz)、3.07(3H，s)、3.19(1H，dd，J＝8.9，8.9Hz)、3.28(1H，dd，J＝9.0，9.0Hz)、3.43(1H，dd，J＝9.0，9.0Hz)、3.50(1H，dd，J＝10.7，6.1Hz)、3.67(1H，dd，J＝10.7，?4.0Hz)、4.02(1H，d，J＝14.5Hz)、4.16(1H，d，J＝14.5Hz)、4.14-4.26(1H，m)、6.88(1H，t，J＝6.2Hz)、7.04(1H，d，J＝8.1Hz)、7.17(1H，d，J＝7.5Hz)、7.18(1H，t，J＝7.5Hz)、7.48(1H，d，J＝8.4Hz)、7.80(1H，d，J＝8.4Hz)

MS(ESI ⁺)：423[M+H] ⁺，440[M+NH ₄] ⁺，445[M+Na] ⁺

The HPLC hold-time: 9.0 minutes

Embodiment 23

[2-(4-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(4-luorobenzyl) phenol is synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 4.9mL), stirred 20 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.04g, THF solution (60mL) 7.75mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-fluorobenzaldehyde (801mg, THF solution (10mL) 6.45mmol).Under uniform temp, stir after 1.5 hours, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates, and obtains the crude product (2.35g) of title compound.In the methanol solution (15mL) of the crude product that obtains, add 20% palladium hydroxide catalyzer (186mg), add 2N-HCl (400 μ L) again.In nitrogen atmosphere, stir after 3 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (996mg, 77%).

¹H-NMR(CDCl ₃)δ：3.95(2H，s)、4.72(1H，s)、7.77(1H，dd，J＝7.9，1.1Hz)、6.88(1H，td，J＝7.5，1.1Hz)、6.96(1H，dd，J＝8.7，8.7Hz)、7.06-7.20(4H，m)

2) [2-(4-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(4-luorobenzyl) phenol (284mg, 1.40mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.928mmol) and the tributylphosphine (0.35mL, 1.40mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 241mg, 1.40mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 21 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 8 → 1: 3)) handle.The crude product that obtains is dissolved in methyl alcohol (4mL)-THF (2mL) mixed solvent, adds 20% palladium hydroxide catalyzer (18.4mg) and 1 2N hydrochloric acid, in nitrogen atmosphere, stirred 1.5 hours.Add saturated sodium bicarbonate water and neutralize, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1 → 8: 1)) make with extra care, obtain title compound (153mg, 46%).

¹H-NMR(CD ₃OD)δ：0.99(1H，ddd，J＝12.9，12.9，12.9Hz)、1.55(1H，m)、2.08(1H，ddd，J＝13.2，3.9，3.9Hz)、3.22(1H，dd，J＝9.0，9.0Hz)、3.30(1H，dd，J＝9.0，9.0Hz)、3.48(1H，dd，J＝8.7，8.7Hz)、3.51(1H，dd，J＝10.8，6.0Hz)、3.70(1H，dd，J＝10.8，4.2Hz)、3.90(1H，d，J＝14.7Hz)、4.02(1H，d，J＝14.7Hz)、4.20(1H，ddd，J＝11.4，9.0，4.8Hz)、6.85(1H，t，J＝7.5Hz)、6.93(1H，dd，J＝8.9，8.9Hz)、7.02(1H，d，J＝8.1Hz)、7.06-7.23(4H，m)

MS(ESI ⁺)：363[M+H] ⁺

The HPLC hold-time: 10.9 minutes

Embodiment 24

[2-(3.4-dimethoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(3, the 4-dimethoxy-benzyl) phenol is synthetic

In nitrogen gas stream, under-78 ℃, ((1.59M 4.4mL), stirred 1 hour under uniform temp the hexane solution of dropping n-Butyl Lithium among the 1.74g, THF solution (30mL) 6.61mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 3,4-dimethoxy benzaldehyde (1.00g, THF solution (8mL) 6.02mmol).Under uniform temp, stir after 1.5 hours, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates, and obtains crude product (2.38g).This crude product is dissolved in the methyl alcohol (20mL), adds 20% palladium hydroxide catalyzer (196mg), add 2N-HCl (30 μ l) again.In nitrogen atmosphere, stir after 23 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (653mg, 44%).

¹H-NMR(CDCl ₃)δ：3.82(3H，s)、3.85(3H，s)、3.94(2H，s)、4.73(1H，s)、6.74-6.82(2H，m)、6.78(1H，s)、6.89(1H，td，J＝7.5，1.1Hz)、?7.08-7.17(2H，m)

2) [2-(3, the 4-dimethoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(3, the 4-dimethoxy-benzyl) adds 2 in the toluene (2.5mL) of phenol (342mg, 1.40mmol)-THF (1.0mL) mixing solutions, 3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (504mg, 0.936mmol) and the tributylphosphine (0.35mL, 1.40mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 242mg, 1.41mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 22 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 3)) handle.The crude product that obtains is dissolved in methyl alcohol (2mL)-THF (2mL) mixed solvent, adds 20% palladium hydroxide catalyzer (21.9mg), in nitrogen atmosphere, stir after 5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (108mg, 38%).

¹H-NMR(CD ₃OD)δ：1.01(1H，ddd，J＝13.1，13.1，11.6Hz)、1.55(1H，m)、2.08(1H，ddd，J＝13.3，3.8，3.8Hz)、3.21(1H，dd，J＝9.2，9.2Hz)、3.29(1H，dd，J＝8.9，8.9Hz)、3.48(1H，dd，J＝9.2，9.2Hz)、3.49(1H，dd，J＝10.7，6.3Hz)、3.70(1H，dd，J＝10.7，4.1Hz)、3.76(3H，s)、3.78(3H，s)、3.87(1H，d，J＝14.8Hz)、3.96(1H，d，J＝14.8Hz)、4.19(1H，ddd，J＝11.5，9.0，4.6Hz)、6.73(1H，dd，J＝8.3，2.0Hz)、6.81(1H，s)、6.82(1H，d，J＝8.3Hz)、6.84(1H，td，J＝7.5，1.2Hz)、7.02(1H，d，J＝7.5Hz)、7.08(1H，dd，J＝7.5，1.5Hz)、7.14(1H，td，J＝7.2，1.7Hz)

MS(ESI ⁺)：405[M+H] ⁺

The HPLC hold-time: 9.7 minutes

Embodiment 25

[2-(4-Ethylbenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-Ethylbenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2.5mL) that discloses 2-(4-Ethylbenzyl) phenol (236mg, 1.11mmol) of record among WO04/052902 or the WO01/074834 etc. in the world, add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (400mg, 0.74mmol) and the tributylphosphine (0.28mL, 1.11mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 191mg, 1.11mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 25 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (4mL) of methyl alcohol-THF (1: 2), adds 20% palladium hydroxide catalyzer (20mg), in nitrogen atmosphere, stir after 1.5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (40mg, 14%).

¹H-NMR(CD ₃OD)δ：0.86-1.00(1H，m)、1.19(3H，t，J＝7.6Hz)、1.45-1.62(1H，m)、2.00-2.11(1H，m)、2.57(2H，q，J＝7.6Hz)、3.16-3.30(2H，m)、3.43-3.49(2H，m)、3.70(1H，dd，J＝10.6，4.1Hz)、3.84-4.02(2H，m)、4.12-4.24(1H，m)、6.83(1H，t，J＝7.4Hz)、6.99-7.16(7H，m)

MS(ESI ⁺)：395[M+Na] ⁺

The HPLC hold-time: 12.3 minutes

Embodiment 26

[2-(4-hydroxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-hydroxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen atmosphere, under-78 ℃, after adding the dichloromethane solution (1.0M, 0.80mL, 0.80mmol) of boron tribromide in the dichloromethane solution (1.3mL) of [2-(4-methoxy-benzyl) the phenyl]-5a-carbon-β-D-glucopyranoside (100mg, 0.27mmol) that in embodiment 1, obtains, remove cooling bath, at room temperature stirred 1 hour.With the reaction solution concentrating under reduced pressure, with the residue that obtains with HPLC (developping solution=methyl alcohol: the 20mM ammonium acetate solution) make with extra care, obtain title compound (45mg, 47%).

¹H-NMR(CD ₃OD)δ：0.92-1.06(1H，m)、1.47-1.67(1H，m)、2.03-2.11(1H，m)、3.18-3.34(2H，m)、3.45-3.52(2H，m)、3.71(1H，dd，J＝10.7，4.1Hz)、3.79-3.95(2H，m)、4.12-4.22(1H，m)、6.65(2H，d，J＝8.4Hz)、6.83(1H，t，J＝7.3Hz)、6.99-7.16(5H，m)

MS(ESI ⁺)：361[M+H] ⁺

The HPLC hold-time: 8.9 minutes

Embodiment 27

[2-(4-cyano group benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-cyano group benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-cyano group benzyl) phenol (291mg, 1.39mmol) toluene (2mL)-THF (1mL) mixed solution in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 14 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains normal hexane (1: 5)) and preparation TLC (developping solution=ethyl acetate: normal hexane (1: 3)) handle, obtain crude product (130mg) with silica gel column chromatography (developping solution=ethyl acetate:.The crude product (55mg) that obtains is dissolved in the methylene dichloride (0.50mL), ice-cold add down dimethyl thioether (0.19mL, 4.4mmol) and boron trifluoride diethyl etherate coordination compound (0.095mL, 0.75mmol).After reaction solution at room temperature stirred 5 hours, under ice-cold, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (17.5mg, 12%).

¹H-NMR(CD ₃OD)δ：0.83-0.96(1H，m)、1.44-1.60(1H，m)、1.99-2.07(1H，m)、3.14-3.32(2H、m)、3.38-3.50(2H，m)、3.67(1H，dd，J＝10.7，4.0Hz)、3.93-4.13(2H，m)、4.15-4.22(1H，m)、6.85(1H，t，J＝7.3Hz)、7.01(1H，d，J＝7.9Hz)、7.11-7.18(2H，m)、7.37(2H，d，J＝8.2Hz)、7.55(2H，d，J＝8.1Hz)

MS(ESI ⁺)：392[M+Na] ⁺

The HPLC hold-time: 10.2 minutes

Embodiment 28

[2-(3-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(3-trifluoro-methoxybenzyl) phenol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 4.3mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.5g, THF solution (95mL) 9.5mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 3-trifluoro-methoxybenzaldehyde (1.5g, THF solution (32mL) 7.9mmol).Under uniform temp, stir after 2 hours, stirred 1 hour down at 0 ℃ again, add entry then, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) handle.The crude product that obtains is dissolved in the methyl alcohol (20mL), adds 20% palladium hydroxide catalyzer (200mg), 2N-HCl (0.187mL).In nitrogen atmosphere, stirred 13 hours.In reaction solution, add salt of wormwood (850mg), at room temperature stir 30 minutes after, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.40g, 99%).

¹H-NMR(CDCl ₃)δ：3.99(2H，s)、4.71(1H，br?s)、6.76(1H，d，J＝7.9Hz)、6.92-6.86(1H，m)、7.02-7.15(5H，m)、7.29(1H，d，J＝7.3Hz)

2) [2-(3-trifluoro-methoxybenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 2-(3-trifluoro-methoxybenzyl) phenol (373mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (10mL) of methyl alcohol-THF (1: 2), adds 20% palladium hydroxide catalyzer (100mg), in nitrogen atmosphere, stir after 13 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (104mg, 26%).

¹H-NMR(CD ₃OD)δ：0.86-1.00(1H，m)、1.45-1.60(1H，m)、2.01-2.09(1H，m)、3.15-3.31(2H，m)、3.41-3.48(2H，m)、3.68(1H，dd，J＝10.7，4.1Hz)、3.88-4.11(2H，m)、4.13-4.95(1H，m)、6.82-6.87(1H，m)、7.00-7.30(7H，m)

MS(ESI ⁺)：429[M+H] ⁺

The HPLC hold-time: 12.4 minutes

Embodiment 29

[2-(4-amino methyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside acetate

1) [2-(4-amino methyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside acetate is synthetic

With [2-(the 4-cyano group benzyl) phenyl]-2 that obtains among the embodiment 27,3,4, the crude product (63mg) of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside is dissolved in the mixing solutions (1mL) of methyl alcohol-THF (1: 2), add 20% palladium hydroxide catalyzer (10mg), in nitrogen atmosphere, stir after 23 hours, catalyzer is filtered, the solvent underpressure distillation is removed, obtain [2-(4-amino methyl benzyl) phenyl]-2,3,4, the crude product of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside.This crude product is dissolved in the methylene dichloride (0.55mL), and (0.22mL, 5.1mmol) (0.11mL 0.86mmol), at room temperature stirred 22 hours with the boron trifluoride diethyl etherate coordination compound at the ice-cold dimethyl thioether of adding down.With the reaction solution concentrating under reduced pressure, with the residue that obtains with HPLC (developping solution=methyl alcohol: the 20mM ammonium acetate solution) make with extra care, obtain title compound (19mg).

¹H-NMR(CD ₃OD)δ：0.85-0.99(1H，m)、1.42-1.58(1H，m)、1.88(3H，s)、1.93-2.01(1H，m)、3.14-3.67(5H，m)、3.87-4.07(2H，m)、4.01(2H，s)、4.11-4.20(1H，m)、6.79-6.85(1H，m)、6.99(1H，d，J＝4.1H)、7.01-7.16(2H，m)、7.25(2H，d，J＝8.4Hz)、7.29(2H，d，J＝8.5Hz)

MS(ESI ⁺)：374[M+H] ⁺

The HPLC hold-time: 7.3 minutes

Embodiment 30

[5-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [5-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 5-methoxyl group-2-(4-methoxy-benzyl) phenol (340mg, 1.39mmol) of record in the open WO04/058682 in the world or WO02/064606 or WO02/044192 etc., add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 17 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 3)) handle.The crude product that obtains is dissolved in the mixing solutions (5mL) of methyl alcohol-THF (1: 2), adds 20% palladium hydroxide catalyzer (50mg), in nitrogen atmosphere, stir after 3 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with TLC (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (119mg, 32%).

¹H-NMR(CD ₃OD)δ：0.84-0.98(1H，m)、1.44-1.60(1H，m)1.98-2.06(1H，m)、3.13-3.47(5H，m)、3.77(3H，s)、3.82(3H，s)、3.71-3.88(2H，m)、4.06-4.16(1H，m)、6.41(1H，dd，J＝2.3，8.2Hz)、6.58(1H，d，J＝2.1Hz)、6.75(2H，d，J＝8.7Hz)、6.94(1H，d，J＝8.2Hz)、7.05(2H，d，J＝8.6Hz)

MS(ESI ⁺)：405[M+H] ⁺

The HPLC hold-time: 10.7 minutes

Embodiment 31

[2-(4-methoxycarbonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) methylol 4-[(2-benzyloxy phenyl)] methyl benzoate synthetic

In nitrogen gas stream, under-78 ℃, ((2.71M 12.1mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 7.84g, THF solution (300mL) 29.8mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-methoxycarbonyl phenyl aldehyde (4.78g, THF solution (100mL) 29.1mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (4.15g, 41%).

¹H-NMR(CDCl ₃)δ：3.06(1H，d，J＝6.2Hz)、3.91(3H，s)、5.02(2H，dd，J＝5.8，11.4Hz)、6.07(1H，d，J＝6.2Hz)、6.94-7.00(2H，m)、7.18-7.42(9H，m)、7.96(2H，d，J＝8.4Hz)

2) 4-(2-benzyloxy benzyl) methyl benzoate is synthetic

In nitrogen gas stream, under-40 ℃, to 4-[(2-benzyloxy phenyl)-methylol] methyl benzoate (4.15g, 11.9mmol) acetonitrile solution (22.7mL) in add triethyl silicane (2.27mL, 13.5mmol) and boron trifluoride diethyl etherate coordination compound (1.52mL, 11.88mmol), under uniform temp, stirred 1.5 hours.After stirring 30 minutes under 0 ℃, add entry again, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (2.39g, 62%).

¹H-NMR(CDCl ₃)δ：3.89(3H，s)、4.05(2H，s)、5.02(2H，d、J＝5.8Hz)、6.92(2H，d、J＝7.9Hz)、7.12-7.36(9H，m)、7.91(2H，d，J＝8.0Hz)

MS(ESI ⁺)：333[M+H] ⁺

3) 4-(2-hydroxybenzyl) methyl benzoate is synthetic

In the methanol solution (70mL) of 4-(2-benzyloxy benzyl) methyl benzoate (2.39g, 7.19mmol), add 20% palladium hydroxide catalyzer (239mg).In nitrogen atmosphere, stir after 5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, obtain title compound (1.16g, 96%).

¹H-NMR(CDCl ₃)δ：3.89(3H，s)、4.04(2H，s)、4.76(1H，s)、6.77(1H，d、J＝8.0Hz)、6.89(1H，t、J＝7.3Hz)、7.13(2H，m)、7.29(2H，d，J＝8.4Hz)、7.94(2H，d，J＝8.0Hz)

MS(ESI ⁺)：243[M+H] ⁺

4) [2-(4-methoxycarbonyl benzyl) phenyl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (6.9mL) of 4-(2-hydroxybenzyl) methyl benzoate (741.4mg, 3.06mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (1.10g, 2.04mmol) and the tributylphosphine (0.77mL, 3.06mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 526.5mg, 3.06mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (429.0mg, 28%).

¹H-NMR(CD ₃OD)δ：1.40(1H，dd、J＝12.0，12.0Hz)、1.65-1.74(1H，m)、2.00-2.09(1H，m)、3.43-3.59(2H，m)、3.84(3H，s)、?4.00(2H，s)、4.32-3.92(8H，m)、6.91(1H，t，J＝8.0Hz)、7.04-7.32(25H，m)，7.87(2H，d，J＝8.0Hz)

5) [2-(4-methoxycarbonyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

With [2-(4-methoxycarbonyl benzyl) phenyl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (38.1mg, 0.05mmol) is dissolved in the mixing solutions (1.5mL) of methyl alcohol-THF (2: 1), add 20% palladium hydroxide catalyzer (5mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (12.9mg, 65%).

¹H-NMR(CD ₃OD)δ：0.89-1.00(1H，m)、1.47-1.62(1H，m)、2.03-2.09(1H，m)、3.16-3.23(2H，m)、3.42-3.49(2H，m)、3.51-3.87(1H，m)、3.95(3H，s)、4.00-4.17(2H，m)、4.19-4.23(1H，m)、6.87(1H，d，J＝7.4Hz)、7.31(1H，d，J＝7.6Hz)、7.12-7.20(2H，m)、7.32(2H，d，J＝8.4Hz)、7.88(2H，d，J＝8.4Hz)

MS(ESI ⁺)：403[M+Na] ⁺

Embodiment 32

[2-(4-formamyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-carboxyl benzyl) phenyl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen atmosphere, at room temperature, to [2-(4-methoxycarbonyl benzyl) phenyl]-2,3,4, add 5N-aqueous sodium hydroxide solution (0.15mL) in ethanol-THF (4: 1) solution (1.5mL) of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (100.0mg, 0.13mmol), stirred 22 hours.Ice-cold following, add the 5N-aqueous hydrochloric acid and neutralize then.Use dichloromethane extraction, dry (sodium sulfate), concentrating under reduced pressure obtains title compound (91.3mg, 94%).

¹H-NMR(CDCl ₃)δ：1.42(1H，ddd、J＝12.4，12.4，12.4Hz)、1.55-1.67(1H，m)、2.00-2.04(1H，m)、3.41-3.61(2H，m)、4.02(2H，s)、4.35-3.92(8H，m)、6.92(1H，t，J＝7.3Hz)、7.05-7.32(25H，m)，7.92(2H，d，?J＝7.7Hz)

MS(ESI ⁺)：749[M+H] ⁺

2) [2-(4-formamyl benzyl) phenyl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen atmosphere, at room temperature, to [2-(4-hydroxycarbonyl group benzyl) phenyl]-2,3,4, the N of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (45.0mg, 0.06mmol), add I-hydroxybenzotriazole 1 hydrate (9.0mg, 0.07mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (12.0mg, 0.07mmol) in dinethylformamide (1.2mL) solution, stir after 1 hour,, stirred 27 hours at the ice-cold ammoniacal liquor (0.5mL) that adds down.Concentrating under reduced pressure is with preparation TLC (developping solution=methyl alcohol: methylene dichloride=1: 10) make with extra care, obtain title compound (39.1mg, 89%).

¹H-NMR(CDCl ₃)δ：1.31-1.49(1H，m)、1.62-1.76(1H，m)、1.96-2.08(1H，m)、3.39-3.66(2H，m)、4.02(2H，s)、4.33-4.96(8H，m)、6.88-6.97(1H，m)、7.04-7.39(25H，m)，7.54-7.61(2H，m)

MS(ESI ⁺)：748[M+H] ⁺

3) [2-(4-formamyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

To [2-(4-formamyl benzyl) phenyl]-2,3,4, add 20% palladium hydroxide catalyzer (5mg) in methyl alcohol-THF (2: 1) solution (3mL) of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (39.1mg, 0.05mmol).In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 5)) make with extra care, obtain title compound (19.2g, 99%).

¹H-NMR(CD ₃OD)δ：0.92(1H，dd，J＝11.7，11.7Hz)、1.48-1.62(1H，m)、1.96-2.08(1H，m)、3.16-3.33(4H，m)、3.42-3.59(2H，m)、3.65-3.73(1H，m)、3.93-4.26(3H，m)、6.87(1H，t、J＝7.3Hz)，7.02-7.21(3H，m)、7.31(2H，d，J＝8.2Hz)、7.74(2H，d，J＝8.1Hz)

MS(ESI ⁺)：388[M+H] ⁺

The HPLC hold-time: 8.0 minutes

Embodiment 33

[2-(4-N, N-formyl-dimethylamino benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) [2-(4-N, N-formyl-dimethylamino benzyl) phenyl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen atmosphere, at room temperature, [2-(the 4-carboxyl benzyl) phenyl] that in embodiment 32, obtains-] 2,3,4, the N of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (45.0mg, 0.06mmo l), add in dinethylformamide (1.2mL) solution]-hydroxybenzotriazole 1 hydrate (9.0mg, 0.07mmol), 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide hydrochloride (12.0mg, 0.07mmol), stir after 1 hour, at the ice-cold N that adds down, the N dimethylamine aqueous solution (0.5mL) stirred 27 hours.Concentrating under reduced pressure is with preparation TLC (methyl alcohol: methylene dichloride=1: 10) make with extra care, obtain title compound (44.1mg, 96%).

¹H-NMR(CDCl ₃)δ：1.42-1.52(1H，m)、1.66-1.78(1H，m)、2.05-2.14(1H，m)、2.83(3H，s)、3.04(3H，s)、3.44-3.68(5H，m)、3.99(2H，s)、4.35-4.53(1H，m)、4.68(2H，s)、4.83-4.94(3H，m)、6.91(1H，t，J＝7.3Hz)、7.04-7.36(27H，m)

MS(ESI ⁺)：776[M+H] ⁺

2) [2-(4-N, N-formyl-dimethylamino benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

To [2-(4-N, N-formyl-dimethylamino benzyl) phenyl]-2,3,4, add 20% palladium hydroxide catalyzer (5mg) in methyl alcohol-THF (2: 1) solution (3mL) of 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside (44.1mg, 0.06mmol).In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 5)) make with extra care, obtain title compound (20.1mg, 87%).

¹H-NMR(CD ₃OD)δ：0.86-1.00(1H，m)、1.45-1.58(1H，m)、1.98-2.06(1H，m)、2.95(3H，s)、3.03(3H，s)、3.13-3.49(5H，m)、3.62-3.68(1H，m)、3.88-4.21(3H，m)、6.91(1H，t，J＝7.2Hz)、6.98-7.15(3H，m)、7.26(4H，s)

MS(ESI ⁺)：416[M+H] ⁺

The HPLC hold-time: 8.9 minutes

Embodiment 34

[2-(4-ethoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(4-ethoxy benzyl)-phenol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.71M 3.8mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.5g, THF solution (90mL) 9.5mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-ethoxy-benzaldehyde (1.29mL, THF solution (30mL) 1.86mmol).Under uniform temp, stir after 2 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) handle.In the methanol solution (26.8mL) of the crude product that obtains, add 20% palladium hydroxide catalyzer (147mg), add 36%HCl (0.4mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (828.1mg, 38%).

¹H-NMR(CDCl ₃)δ：1.39(3H，t、J＝7.0Hz)、3.93(2H，s)、3.99(2H，q、J＝7.0Hz)、6.77-6.90(4H，m)、7.09-7.14(4H，m)

2) [2-(4-ethoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3.2mL) of 2-(4-ethoxy benzyl) phenol (319.6mg, 1.4mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the methyl alcohol (5mL), adds 20% palladium hydroxide catalyzer (56mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (133.5mg, 36%).

¹H-NMR(CD ₃OD)δ：0.89-1.03(1H，m)、1.35(3H，t，J＝7.1Hz)，1.48-1.62(1H，m)、2.02-2.11(1H，m)、3.18-3.33(3H，m)、3.35(2H，s)，?3.44-3.52(2H，m)、3.68-3.74(1H，m)、3.81-4.02(4H，m)、4.13-4.23(1H，m)、6.74-6.87(4H，m)、6.99-7.17(4H、m)

MS(ESI ⁺)：411[M+Na] ⁺

The HPLC hold-time: 11.4 minutes

Embodiment 35

[2-(4-difluoro-methoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(4-difluoro-methoxy benzyl) phenol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.71M 3.8mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.5g, THF solution (90mL) 9.5mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-difluoro-methoxy phenyl aldehyde (1.23mL, THF solution (30mL) 1.86mmol).Under uniform temp, stir after 2 hours, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) handle.In the methanol solution (26.8mL) of the crude product that obtains, add 20% palladium hydroxide catalyzer (147mg), add concentrated hydrochloric acid (0.4mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.03g, 42%).

¹H-NMR(CDCl ₃)δ：3.97(2H，s)、6.46(1H，t，J＝74.4Hz)6.77(1H，d、J＝8.0Hz)、6.87-6.91(1H，t，J＝7.3Hz)、7.03(2H，d，J＝8.4Hz)、7.09-7.15(2H，m)、7.21(2H，d，J＝8.0Hz)

2) [2-(4-difluoro-methoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3.2mL) of 2-(4-difluoro-methoxy benzyl) phenol (350.0mg, 1.4mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the methyl alcohol (5mL), adds 20% palladium hydroxide catalyzer (69mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (153.1mg, 40%).

¹H-NMR(CD ₃OD)δ：0.87-1.01(1H，m)、1.48-1.62(1H，m)、2.01-2.11(1H，m)、3.17-3.34(2H，m)、3.43-3.54(2H，m)、3.67-3.73(1H，m)、3.96(2H，dd、J＝22.9，14.7Hz)、4.14-4.26(1H，m)、6.72(1H，t，J＝74.5Hz)、6.83-7.25(8H，m)

MS(ESI ⁺)：433[M+Na] ⁺

The HPLC hold-time: 11.6 minutes

Embodiment 36

[2-(4-tertiary butyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl)-(4-tert-butyl-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 5.65mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 3.3g, THF solution (126mL) 12.5mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-tert.-butylbenzene formaldehyde (1.68g, THF solution (42mL) 10.4mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.17g, 60%).

¹H-NMR(CDCl ₃)δ：1.32(9H，s)、2.86(1H，br?s)、5.02(2H，s)、6.03(1H，s)、6.03-7.00(2H，m)、7.13-7.39(11H，m)

2) 2-(4-tertiary butyl benzyl) phenol is synthetic

In the methanol solution (27mL) of (2-benzyloxy phenyl)-(4-tert-butyl-phenyl) methyl alcohol (2.17g, 6.26mmol), add 20% palladium hydroxide catalyzer (217mg), add 2N-HCl (0.52mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (1.3g, 86%).

¹H-NMR(CDCl ₃)δ：1.29(9H，s)、3.96(2H，s)、4.65(1H，s)、?6.75-6，91(2H，m)、7.09-7.32(6H，m)

3) [2-(4-tertiary butyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 2-(4-tertiary butyl benzyl) phenol (334mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (12mL) of methyl alcohol-THF (1: 1), adds 20% palladium hydroxide catalyzer (60mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (57mg, 15%).

¹H-NMR(CD ₃OD)δ：0.89-1.01(1H，m)、1.29(9H，s)、1.53-1.59(1H，m)、2.04-2.11(1H，m)、3.19-3.34(2H，m)、3.45-3.51(2H，m)、3.71(1H，dd，10.8，4.5Hz)、3.95(2H，m)、4.19(1H，m)、6.84(1H，m)、7.01-7.17(5H，m)、7.26-7.28(2H，m)

MS(ESI ⁺)：401[M+H] ⁺

The HPLC hold-time: 13.7 minutes

Embodiment 37

[2-(4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy phenyl) p-methylphenyl methyl alcohol is synthetic

In nitrogen gas stream, under-78 ℃, ((2.44M 5.65mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 3.3g, THF solution (126mL) 12.54mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 4-tolyl aldehyde (1.28g, THF solution (42mL) 10.6mmol).Under uniform temp, stir after 1 hour, add entry, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.3g, 71%).

¹H-NMR(CDCl ₃)δ：2.33(3H，s)、2.87(1H，s)、5.02(2H，s)、?6.03(1H，s)、6.09-6.99(2H，m)、7.09-7.34(11H，m)

2) 2-(4-methyl-benzyl) phenol is synthetic

In the methanol solution (27mL) of (2-benzyloxy phenyl) p-methylphenyl methyl alcohol (1.5g, 4.43mmol), add 20% palladium hydroxide catalyzer (150mg), add 2N-HCl (0.37mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (617mg, 70%).

¹H-NMR(CDCl ₃)δ：1.55(3H，s)、3.95(2H，s)、4.65(1H，s)、6.75-6，90(2H，m)、7.09-7.25(6H，m)

3) [2-(4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (2mL) of 2-(4-methyl-benzyl) phenol (275mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 239mg, 1.39mmol).Make reaction solution slowly rise to room temperature on one side, Yi Bian stirred 20 hours.With the reaction solution concentrating under reduced pressure, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) handle.The crude product that obtains is dissolved in the mixing solutions (8mL) of methyl alcohol-THF (1: 1), adds 20% palladium hydroxide catalyzer (44mg), in nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (20mg, 6%).

¹H-NMR(CD ₃OD)δ：0.84-0.97(1H，m)、1.44-2.03(1H，m)、1.96-2.03(1H，m)、2.22(3H，s)、3.13-3.30(2H，m)、3.39-3.46(2H，m)、3.64(1H，dd，J＝10.8，4.5Hz)、3.95(2H，m)、4.12(1H，m)、6.76-6.81(1H，m)、6.92-7.03(5H，m)、7.06-7.11(2H，m)

MS(ESI ⁺)：381[M+Na] ⁺

The HPLC hold-time: 11.4 minutes

Embodiment 38

[2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-yl]-5a-carbon-β-D-glucopyranoside

1) 3-benzyloxy-2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene is synthetic

In nitrogen gas stream, under 0 ℃, spend 5 fens clockwise to disclose method synthetic (3-benzyloxy-5-trifluoromethyl thiophene-2-yl)-(4-p-methoxy-phenyl) ketone [methanone] (220.2mg that WO 04/007517 puts down in writing according to the world, 0.56mmol) and triethyl silicane (dropping trifluoroacetic acid (3mL) among the 1.34mL, dichloromethane solution 8.41mmol) (1.1mL).Under uniform temp, stir after 6 hours 45 minutes, and the interpolation triethyl silicane (0.9mL, 5.61mmol).Under uniform temp, stir after 16 hours 45 minutes, the reaction mixture concentrating under reduced pressure.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (108.8mg, 51%).

¹H-NMR(CDCl ₃)δ：3.79(3H，s)、3.96(2H，s)、5.04(2H，s)、6.82(2H，d，J＝8.6Hz)、7.11(2H，d，J＝8.6Hz)、7.16(1H，s)、7.30-7.41(5H，m)

2) 2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-phenol [thiophen-3-ol] is synthetic

In nitrogen gas stream, under-78 ℃, to (3-benzyloxy-2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene (170.5mg, 0.45mmol) dichloromethane solution (4.5mL) in add the dichloromethane solution (0.47mL of boron tribromide dimethyl thioether coordination compound, 0.47mmol), under uniform temp, stirred 5 minutes, stirred 11 hours down at 0 ℃.In reaction mixture, add entry, use dichloromethane extraction.With organic layer saturated sodium bicarbonate aqueous solution and saturated common salt water washing, after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (117.0mg, 90%).

¹H-NMR(CDCl ₃)δ：3.80(3H，s)、3.97(2H，s)、4.47(1H，s)、6.87(2H，d，J＝8.6Hz)、6.98(1H，s)、7.19(2H，d，J＝8.6Hz)

3) [2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-yl]-2,3,4,6-four-O-benzyl-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen gas stream, under ice-cold, to 2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-phenol (117mg, 0.41mmol) toluene solution (0.85mL) in add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (146mg, 0.27mmol) and the tributylphosphine (0.10mL, 0.41mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 70mg, 0.41mmol).Reaction mixture was at room temperature stirred 18.5 hours.With reaction mixture with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10～1: 8)) handle.With the product that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 8)) make with extra care, obtain title compound (47.2mg).

¹H-NMR(CDCl ₃)δ：1.56-1.80(2H，m)、1.96-2.10(1H，m)、3.40-3.70(5H，m)、3.75(3H，s)、3.96(2H，s)、3.96-4.16(1H，m)、4.44(2H，s)、4.53(1H，d，J＝11.0Hz)、4.70-5.00(5H，m)、6.79(2H，d，J＝8.6Hz)、7.06-7.38(23H，m)

4) [2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-yl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, with [2-(4-methoxy-benzyl)-5-trifluoromethyl thiophene-3-yl]-2,3,4, (45.2mg 0.056mmol) is dissolved in the methylene dichloride (0.5mL) 6-four-O-benzyl-5a-carbon-β-D-glucopyranoside, at the ice-cold dimethyl thioether (0.145mL that adds down, 3.35mmol) and the boron trifluoride diethyl etherate coordination compound (0.07mL, 0.56mmol).Reaction mixture was stirred 5 minutes under uniform temp, at room temperature stir 19 hours after, at ice-cold saturated sodium bicarbonate aqueous solution and the water of adding down, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with preparation TLC (developping solution=normal hexane: acetone (1: 1)) make with extra care, obtain title compound (12.2mg, 49%).

¹H-NMR(CD ₃OD)δ：1.15-1.35(1H，m)、1.40-1.65(1H，m)、1.95-2.15(1H，m)、3.15-3.35(2H，m)、3.35-3.60(2H，m)、3.65-3.80(1H，m)、3.75(3H，m)、3.90-4.06(1H，m)、4.01(2H，m)、6.84(2H，d，J＝8.3Hz)、7.16(2H，d，J＝8.3Hz)、7.40(1H，s)

MS(ESI ⁺)：448[M] ⁺

The HPLC hold-time: 12.4 minutes

Embodiment 39

[3-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-benzyloxy-6-methoxybenzoic acid benzyl ester is synthetic

In nitrogen gas stream, under ice-cold, Yi Bian stir the mixture of 6-methoxyl group Whitfield's ointment (5.07g, 30.15mmol) and sodium hydride (60%w/w, 3.02g, 75.38mmol), Yi Bian add DMF (30mL).Under uniform temp, stir after 10 minutes, spend 5 minutes and add bromotoluene (8.95mL, 75.38mmol), reaction mixture was stirred 30 minutes under uniform temp, at room temperature stirred 2.5 hours.Ice-cold saturated aqueous ammonium chloride and the water of adding is down used extracted with diethyl ether.With organic layer water and saturated aqueous ammonium chloride washing, after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10～1: 5)) make with extra care, obtain title compound (6.24g, 59%).

¹H-NMR(CDCl ₃)δ：3.81(3H，s)、5.08(2H，s)、5.35(2H，s)、6.55(1H，d，J＝5.9Hz)、6.58(1H，d，J＝5.9Hz)、7.15-7.45(11H，m)

2) (2-benzyloxy-6-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, at room temperature, spend 15 minutes the clockwise lithium aluminium hydride (0.88g, 23.14mmol) ether suspension (35mL) in add the diethyl ether solution (20mL) of 2-benzyloxy-6-methoxybenzoic acid benzyl ester (6.2g, 17.80mmol).Reaction mixture was stirred 2 hours under reflux.After ice-cold dropping ethyl acetate (2mL) down, drip saturated Rochelle [Rochelle] salt brine solution (20mL), mixture was at room temperature stirred 20 minutes.Use diatomite filtration, in filtrate, add saturated Rochelle's salt solution (15mL), use extracted with diethyl ether.After organic layer saturated common salt water washing, drying (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ether: normal hexane (1: 1)) make with extra care, obtain title compound (4.75g, 100%).

¹H-NMR(CDCl ₃)δ：2.48(1H，t，J＝6.8Hz)、3.85(3H，s)、4.84(2H，d，J＝6.8Hz)、5.10(2H，s)、6.58(1H，d，J＝8.4Hz)、6.62(1H，d，J＝8.2Hz)、7.20(1H，dd，J＝8.4Hz，8.2Hz)、7.28-7.47(5H，m)

3) (2-benzyloxy-6-p-methoxy-phenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, place water-bath to cool off the dichloromethane solution (14.5mL) of (2-benzyloxy-6-p-methoxy-phenyl) methyl alcohol (3.52g, 14.41mmol) and N-methylmorpholine N-oxide compound (NMO, 2.53g, 21.61mmol), add four n-propyls and cross ruthenic acid ammonium (TPAP, 152mg, 0.43mmol).Reaction mixture was stirred 20 minutes under uniform temp, at room temperature stir 1.75 hours after, use diatomite filtration, underpressure distillation removes desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 3～1: 2.5)) handle.The compound dissolution that obtains in THF, with the water-bath cooling, is dripped the THF solution (0.5M, 30.3mL) of 4-p-methoxy-phenyl magnesium bromide in nitrogen gas stream.After at room temperature stirring 1.25 hours, at room temperature add saturated aqueous ammonium chloride, use extracted with diethyl ether.Organic layer is washed with saturated aqueous ammonium chloride, and after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4～1: 3.5)) make with extra care, obtain title compound (3.66g, 72%).

¹H-NMR(CDCl ₃)δ：3.78(3H，s)、3.81(3H，s)、4.28(1H，d，J＝11.7Hz)、4.99(1H，d，J＝11.5Hz)5.06(1H，d，J＝11.5Hz)、6.33(1H，d，J＝11.7Hz)、6.61(1H，d，J＝7.6Hz)、6.64(1H，d，J＝7.6Hz)、6.80(2H，d，J＝8.7Hz)、7.10-7.40(8H，m)

4) 3-methoxyl group-2-(4-methoxy-benzyl) phenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy-6-p-methoxy-phenyl)-(4-p-methoxy-phenyl) methyl alcohol (2.13g, 6.08mmol), add 20% palladium hydroxide catalyzer (0.32g), add 2N-HCl (1.8mL) again.In nitrogen atmosphere, stir after 24 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (1.31g, 89%).

¹H-NMR(CDCl ₃)δ：3.76(3H，s)、3.82(3H，s)、3.98(2H，s)、4.67(1H，s)、6.45(1H，d，J＝8.1Hz)、6.52(1H，d，J＝8.2Hz)、6.79(1H，d，J＝8.6Hz)、7.07(1H，dd，J＝8.1Hz，8.2Hz)、7.17(1H，d，J＝8.6Hz)

5) [3-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene-THF solution (toluene 2.5mL, THF 0.3mL) of 3-methoxyl group-2-(4-methoxy-benzyl) phenol (343mg, 1.40mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (504mg, 0.94mmol) and the tributylphosphine (0.35mL, 1.40mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 242mg, 1.40mmol).Reaction mixture was stirred 1.25 hours down ice-cold, at room temperature stirred 22 hours.With reaction solution with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10～1: 5)) handle.The crude product that obtains is dissolved in the mixing solutions (10mL) of methyl alcohol-THF (1: 4), adds 20% palladium hydroxide catalyzer (94mg), in nitrogen atmosphere, stir after 5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (15: 1～10: 1)) make with extra care, obtain title compound (121mg, 32%).

¹H-NMR(CD ₃OD)δ：0.85-1.05(1H，m)、1.40-1.65(1H，m)、1.95-2.15(1H，m)、3.10-3.30(2H，m)、3.40-3.55(2H，m)、3.60-3.75(1H，m)、3.71(3H，s)、3.79(3H，s)、3.92(2H，s)、4.05-4.25(1H，m)、6.59(1H，d，J＝8.2Hz)、6.65-6.75(3H，m)、7.05-7.15(3H，m)

MS(ESI ⁺)：405[M+H] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 40

[2-(4-methoxy-benzyl)-3-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside

1) (2-benzyloxy-6-aminomethyl phenyl) methyl alcohol is synthetic

In nitrogen gas stream, at room temperature, spend 10 minutes the clockwise lithium aluminium hydride (0.82g, 21.50mmol) ether suspension (30mL) in add the diethyl ether solution (15mL) of 2-benzyloxy-6-tolyl acid ethyl ester (4.47g, 16.54mmol).Reaction mixture was stirred 1 hour under reflux.After ice-cold dropping ethyl acetate (2mL) down, drip saturated Rochelle's salt solution (20mL), mixture was at room temperature stirred 1 hour.Use diatomite filtration, in filtrate, add saturated Rochelle's salt solution (10mL), use extracted with diethyl ether.With organic layer saturated common salt water washing, after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (3.84g, 100%).

¹H-NMR(CDCl ₃)δ：2.20(1H，d，J＝6.6Hz)、2.40(3H，s)、4.79(2H，d，J＝6.6Hz)、5.11(2H，s)、6.83(2H，d，J＝7.9Hz)、7.15(1H，t，J＝7.9Hz)、7.25-7.50(5H，m)

2) 2-benzyloxy-6-tolyl aldehyde is synthetic

In nitrogen gas stream, the dichloromethane solution (10mL) of (2-benzyloxy-6-aminomethyl phenyl) methyl alcohol (3.46g, 15.16mmol) and N-methylmorpholine N-oxide compound (NMO, 2.66g, 22.73mmol) is cooled off with water-bath, add four n-propyls and cross ruthenic acid ammonium (TPAP, 152mg, 0.43mmol).Reaction mixture after stirring 1.75 hours under the uniform temp, is used diatomite filtration, and underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (3.08g, 90%).

¹H-NMR(CDCl ₃)δ：2.59(3H，s)、5.16(2H，s)、6.82(1H，d，J＝7.3Hz)、6.90(1H，d，J＝8.4Hz)、7.25-7.50(6H，m)、10.73(1H，s)

3) (2-benzyloxy-6-aminomethyl phenyl)-(4-p-methoxy-phenyl) methyl alcohol is synthetic

In nitrogen gas stream, place water-bath to cool off the THF solution (10mL) of 2-benzyloxy-6-tolyl aldehyde (3.08g, 13.6mmol), drip the THF solution (0.5M, 30.3mL) of 4-p-methoxy-phenyl magnesium bromide.After at room temperature stirring 1.75 hours,, use extracted with diethyl ether at the ice-cold saturated aqueous ammonium chloride that adds down.Organic layer is washed with saturated aqueous ammonium chloride, and after dry (anhydrous sodium sulphate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 6～1: 5)) make with extra care, obtain title compound (4.57g, 100%).

¹H-NMR(CDCl ₃)δ：2.38(3H，s)、3.80(3H，s)、4.09(1H，d，J＝11.2Hz)、4.88(1H，d，J＝11.5Hz)、5.00(1H，d，J＝11.5Hz)、6.03(1H，d，J＝11.2Hz)、6.75-6.90(4H，m)、6.90-7.05(2H，m)、7.10-7.35(6H，m)

4) 2-(4-methoxy-benzyl)-3-methylphenol is synthetic

In the methanol solution (50mL) of (2-benzyloxy-6-aminomethyl phenyl)-(4-p-methoxy-phenyl) methyl alcohol (2.39g, 7.15mmol), add 20% palladium hydroxide catalyzer (0.36g), add 36%HCl (0.36mL) again.In nitrogen atmosphere, stir after 11 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.40g, 86%).

¹H-NMR(CDCl ₃)δ：2.28(3H，s)、3.76(3H，s)、3.99(2H，s)、4.61(1H，s)、6.67(1H，d，J＝8.1Hz)、6.70-6.85(3H，m)、6.95-7.15(3H，m)

5) [2-(4-methoxy-benzyl)-3-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene-THF solution (toluene 1mL, THF 0.1mL) of 2-(4-methoxy-benzyl)-3-methylphenol (318mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 242mg, 1.40mmol).Reaction mixture was stirred 10 minutes down ice-cold, at room temperature stirred 23 hours.With reaction solution with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 7～1: 6)) handle.The crude product that obtains is dissolved in the mixing solutions (4mL) of methyl alcohol-THF (1: 3), adds 20% palladium hydroxide catalyzer (66mg), in nitrogen atmosphere, stir after 6.5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (55mg, 15%).

¹H-NMR(CD ₃OD)δ：0.85-1.05(1H，m)、1.45-1.65(1H，m)、2.00-2.15(1H，m)、2.21(3H，s)、3.15-3.30(2H，m)、3.40-3.55(2H，m)、3.65-3.75(1H，m)、3.72(3H，s)、3.94(1H，d，J＝15.0Hz)、4.06(1H，d，J＝15.0Hz)、4.05-4.20(1H，m)、6.70-6.80(3H，m)、6.91(1H，d，J＝8.2Hz)、6.95-7.10(3H，m)

MS(ESI ⁺)：411[M+Na] ⁺

The HPLC hold-time: 11.2 minutes

Embodiment 41

[2-(3-fluoro-4-methoxy-benzyl) phenyl]-5a-carbon-α-D-glucopyranoside

1) synthesizing of (2-benzyloxy phenyl)-(3-fluoro-4-p-methoxy-phenyl) methyl alcohol

In nitrogen gas stream, under-78 ℃, ((1.54M 6.79mL), stirred 30 minutes under uniform temp the hexane solution of dropping n-Butyl Lithium among the 2.5g, THF solution (30mL) 9.50mmol) to 1-benzyloxy-2-bromobenzene.Under-78 ℃, in this solution, drip 3-fluoro-4-methoxybenzaldehyde (1.32g, THF solution (8mL) 8.56mmol).Under uniform temp, stir after 1 hour, add saturated aqueous ammonium chloride, use ethyl acetate extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (2.79g, 96%).

¹H-NMR(CDCl ₃)δ：2.92(1H，d，J＝5.8Hz)、3.87(3H，s)、5.03(2H，s)、5.98(1H，d，J＝6.0Hz)、6.85-7.10(5H，m)、7.21-7.35(7H，m)

2) 2-(3-fluoro-4-methoxy-benzyl) phenol is synthetic

In the methanol solution (29mL) of (2-benzyloxy phenyl)-(3-fluoro-4-p-methoxy-phenyl) methyl alcohol (1.50g, 4.43mmol), add 20% palladium hydroxide catalyzer (150mg), add 2N-HCl (2mL) again.In nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (0.95g, 92%).

¹H-NMR(CDCl ₃)δ：3.85(3H，s)、3.91(2H，s)、4.69(1H，br?s)、6.77(1H，dd，J＝1.1，8.0Hz)、6.84-6.97(4H，m)、7.09-7.16(2H，m)

3) [2-(3-fluoro-4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under ice-cold, in the toluene solution (3mL) of 2-(3-fluoro-4-methoxy-benzyl) phenol (323mg, 1.39mmol), add 2,3,4, behind 6-four-O-benzyl-5a-carbon-α-D-Glucopyranose (500mg, 0.93mmol) and the tributylphosphine (0.35mL, 1.39mmol), under uniform temp, add tetramethyl-azodicarboxy acid amides (TMAD, 242mg, 1.40mmol).Reaction mixture is slowly risen to room temperature on one side, Yi Bian stirred 40.5 hours.With reaction solution with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 6)) handle.The crude product that obtains is dissolved in the mixing solutions (6mL) of methyl alcohol-THF (1: 2), adds 20% palladium hydroxide catalyzer (65mg), in nitrogen atmosphere, stir after 2 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (78mg, 21%).

¹H-NMR(CD ₃OD)δ：0.85-1.05(1H，m)、1.40-1.65(1H，m)、1.95-2.15(1H，m)、3.35-3.60(2H，m)、3.60-4.00(3H，m)、3.81(3H，s)、4.05-4.25(1H，m)，6.70-7.20(7H，m)

MS(ESI ⁺)：392[M] ⁺

The HPLC hold-time: 10.7 minutes

Embodiment 42

[4-(4-cyclopropyl-benzyl) pyridin-3-yl]-5a-carbon-β-D-glucopyranoside

1) 3-(2-trimethylsilylethoxy) methoxyl group) pyridine is synthetic

(3.85g, 96.3mmo1) uses hexane wash with sodium hydride, adds glycol dimethyl ether (90mL).Under ice-cold, spend 10 minutes and add 3-pyridone (4.97g, 52.3mmol).Stir after 10 minutes, under ice-cold, spend 25 minutes and add 2-(trimethyl silyl) ethoxyl methyl chlorine (10.0mL, 56.5mmol).After at room temperature stirring 14.5 hours, in ice-cold downhill reaction liquid, add entry, use extracted with diethyl ether, with the organic layer anhydrous magnesium sulfate drying, under reduced pressure concentrate, with the residue that obtains with silica gel flash distillation column chromatography (developping solution=hexane: ethyl acetate=3: 1) make with extra care, obtain title compound (10.8g, 92%).

¹H-NMR(CDCl ₃)δ：0.00(9H，s)、0.93-0.98(2H，m)、3.73-3.79(2H，m)、5.24(2H，s)、7.18-7.23(1H，m)、7.34-7.38(1H，m)、8.25(1H，dd、J＝4.7，1.4Hz)、8.40(1H，dd，J＝3.0，0.6Hz)

2) synthesizing of (4-cyclopropyl phenyl)-[3-(2-trimethylsilylethoxy) methoxyl group) pyridin-4-yl] methyl alcohol

In nitrogen gas stream, under-70 ℃, spend 25 minutes clockwise 3-(2-trimethylsilylethoxy) methoxyl group) pyridine (1.77g, 7.85mmol) anhydrous THF solution (31mL) in drip the Skellysolve A solution (1.47M, 6.20mL) of tert-butyl lithium.After stirring 1 hour under-70 ℃, spend the diethyl ether solution (10mL) that dripped 4-cyclopropyl-phenyl formaldehyde (1.49g, 10.19mmol) in 25 minutes.Stirred 2 hours down and at room temperature stirred 2 hours at-70 ℃.Add saturated aqueous ammonium chloride, use extracted with diethyl ether, the organic layer anhydrous magnesium sulfate drying.After the filtration, underpressure distillation removes desolvates, with the residue that obtains with silica gel flash distillation column chromatography (developping solution=normal hexane: ethyl acetate (2: 1)) make with extra care, obtain title compound (2.17g, 74%).

¹H-NMR(CDCl ₃)δ：-0.04(9H，s)、0.61-0.66(2H，m)、0.84-0.96(4H，m)、1.79-1.90(1H，m)、3.48-3.59(2H，m)、5.13(2H，dd、J＝22.8，6.9Hz)、6.00(1H，s)、6.97-6.99(2H，m)、7.20-7.23(2H，m)、7.48(1H，d、J＝4.9Hz)、8.18(1H，d，J＝4.9Hz)、8.27(1H，s)

3) synthesizing of (4-cyclopropyl phenyl)-[3-(2-trimethylsilylethoxy) methoxyl group)-pyridin-4-yl] ketone

In nitrogen gas stream, to (4-cyclopropyl phenyl)-[3-(2-trimethylsilylethoxy) methoxyl group) pyridin-4-yl] methyl alcohol (2.17g, 5.84mmol) dichloromethane solution (31mL) in add Dess-Martin Periodinane (2.71g, 6.39mmol), at room temperature stirred 1.5 hours.(0.27g 0.64mmol), stirred 1.5 hours to add Dess-Martin Periodinane again.Insolubles is filtered, this filtrate is used saturated sodium bicarbonate aqueous solution, saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with amino silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 1)) make with extra care, obtain title compound (1.96g, 91%).

¹H-NMR(CDCl ₃)δ：-0.04(9H，s)、0.76-0.90(4H，m)、1.05-1.12(2H，m)、1.92-1.98(1H，m)、3.56-3.62(2H，m)、5.17(2H，s)、7.09-7.13(2H，m)、7.19-7.21(1H，m)、7.67-7.71(2H，m)、8.40(1H，d，J＝4.67Hz)、8.65(1H，s)

4) synthesizing of (4-cyclopropyl phenyl)-(3-pyridone-4-yl) ketone

In the THF solution (49mL) of (4-cyclopropyl phenyl)-[3-(2-trimethylsilylethoxy) methoxyl group) pyridin-4-yl] ketone (1.96g, 5.30mmol), add tosic acid 1 hydrate (3.03g, 15.9mmol), stirred 1 hour down at 65 ℃.After being cooled to room temperature, add saturated sodium bicarbonate aqueous solution, use extracted with diethyl ether, the organic layer anhydrous magnesium sulfate drying.After the filtration, underpressure distillation removes desolvates, with the residue that obtains with silica gel flash distillation column chromatography (developping solution=normal hexane: ethyl acetate (2: 3)) make with extra care, obtain title compound (1.10g, 87%).

¹H-NMR(CDCl ₃)δ：0.80-0.86(2H，m)、1.09-1.16(2H，m)、1.97-2.03(1H，m)、7.18-7.22(2H，m)、7.42(1H，dd 、J＝5.2，0.6Hz)、7.63-7.68(2H，m)、8.24(1H，d，J＝5.2Hz)、8.59(1H，d、J＝0.6Hz)、11.15(1H，s)

5) (4-cyclopropyl phenyl)-[3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridin-4-yl] ketone synthetic

In nitrogen gas stream, under ice-cold, to (4-cyclopropyl phenyl)-(3-pyridone-4-yl) ketone (0.18g, 0.74mmol), (1S, 2S, 3S, 4R, 5R)-2,3, slowly drip diisopropyl azo-2-carboxylic acid (0.14mL, 0.72mmol) in the mixture of 4-three benzyloxies-5-benzyloxymethyl hexalin (0.20g, 0.37mmol), triphenylphosphine (0.19g, 0.74mmol) and toluene (1.3mL).After at room temperature stirring 3 hours, underpressure distillation removes desolvates, with the residue that obtains with silica gel flash distillation column chromatography (developping solution=normal hexane: ethyl acetate (2: 3)) make with extra care, obtain title compound (0.20g, 71%).

¹H-NMR(CDCl ₃)δ：0.67-0.73(2H，m)、1.00-1.06(2H，m)、1.39-1.47(1H，m)、1.81-1.88(1H，m)、2.09-2.16(1H，m)、3.37-3.58(5H，m)、4.36-4.51(6H，m)、4.76-4.86(3H，m)、?6.98-7.07(4H，m)、7.13-7.35(19H，m)、7.62-7.66(2H，m)、8.34(1H，d，J＝4.9Hz)、8.54(1H，s)

6) (4-cyclopropyl phenyl)-[3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridin-4-yl] methyl alcohol synthetic

Under ice-cold, to (4-cyclopropyl phenyl)-[3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridin-4-yl] (0.20g adds sodium borohydride (40mg in THF 0.26mmol) (1.37mL)-water (0.67mL) solution to ketone, 1.06mmol), at room temperature stirred 14.5 hours.In reaction mixture, add THF,, stirred 10 minutes at the ice-cold concentrated hydrochloric acid (0.2mL) that adds down.Add saturated aqueous sodium carbonate, at room temperature stirred 10 minutes.Use ethyl acetate extraction, after organic layer drying (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (3: 2)) make with extra care, obtain title compound (0.20g, 100%) as non-enantiomer mixture.

¹H-NMR(CDCl ₃)δ：0.47-0.53(1H，m)，0.58-0.63(1H，m)、0.80-0.92(2H，m)、1.09-1.27(2H，m)、1.68-1.84(2H，m)、3.32-3.64(5H，m)、4.34-4.53(4H，m)、4.70-4.88(5H，m)、5.84(0.5H，s)、5.96(0.5H，s)，6.85-6.97(3H，m)、7.05-7.35(21H，m)、7.43-7.48(1H，m)、8.20-8.24(2H，m)

MS(ESI ⁺)：762[M+H] ⁺

7) 4-[chloro-(4-cyclopropyl phenyl) methyl]-3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridine synthetic

In nitrogen gas stream, under ice-cold, to (4-cyclopropyl phenyl)-[3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridin-4-yl] methyl alcohol (0.20g, 0.26mmol) dichloromethane solution (3.0mL) in add thionyl chloride (0.05mL 0.68mmol), at room temperature stirred 2 hours.Add saturated aqueous sodium carbonate in reaction mixture, use dichloromethane extraction, after organic layer drying (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 1)) make with extra care, obtain title compound (0.20g, 100%) as non-enantiomer mixture.

¹H-NMR(CDCl ₃)δ：0.51-0.53(1H，m)，0.61-0.64(1H，m)、0.83-0.93?(2H，m)、1.10-1.18(1H，m)、1.66-1.77(3H，m)、2.15-2.27(1H，m)、3.30-3.66(5H，m)、4.38-4.55(4H，m)、4.83-4.91(4H，m)、6.23(0.5H，s)、6.39(0.5H，s)、6.85-6.96(3H，m)、7.11-7.33(21H，m)、7.54-7.58(1H，m)、8.26-8.42(2H，m)

MS(ESI ⁺)：780[M+H] ⁺

8) 4-(4-cyclopropyl benzyl)-3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) pyridine synthetic

In nitrogen gas stream, to 4-[chloro-(4-cyclopropyl phenyl) methyl]-3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) (0.22g adds zinc (0.14g, 2.14mmol) in methylene dichloride 0.28mmol) (4.1mL)-acetate (12.4mL) solution to pyridine, at room temperature stirs 14 hours.Add ethyl acetate, with the saturated aqueous sodium carbonate washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 1)) make with extra care, obtain title compound (0.14g, 67%).

¹H-NMR(CDCl ₃)δ：0.57-0.62(2H，m)、0.86-0.92(2H，m)、1.51-1.59(1H，m)、1.70-1.85(2H，m)、2.08-2.15(1H，m)、3.44(1H，dd，J＝9.1，2.5Hz)、3.53-3.70(4H，m)、3.87(2H，d，J＝1.6Hz)、4.42-4.54(4H，m)、4.71(2H，dd，J＝17.6，10.7Hz)，4.83-4.93(3H，m)、6.90-7.34(25H，m)、8.11(1H，d、J＝4.7Hz)、8.35(1H，s)

9) [4-(4-cyclopropyl benzyl) pyridin-3-yl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under-78 ℃, to 4-(4-cyclopropyl benzyl)-3-((1R, 2S, 3S, 4R, 5R)-2,3, pyridine (136mg 4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy), 0.18mmol) dichloromethane solution (7.1mL) in add the dichloromethane solution (1.0M, 1.00mL, 1.00mmol) of penta-methyl benzene (0.40g, 2.70mmol), boron trichloride, stirred 3.5 hours down at-78 ℃.After adding methyl alcohol (1.7mL), add the methanol solution (1.0M, 4mL) of sodium methylate, at room temperature stirred 10 minutes.Insolubles is filtered, this filtrate decompression is concentrated.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (5: 1)) make with extra care, obtain title compound (66mg, 95%).

¹H-NMR(CD ₃OD)δ：0.60-0.65(2H，m)、0.88-0.95(2H，m)、1.06-1.19(1H，m)、1.56-1.61(1H，m)、1.81-1.88(1H，m)、2.05-2.12(1H，m)、3.20-3.27(2H，m)、3.47-3.55(2H，m)、3.72(1H，dd，J＝10.7，3.8Hz)、3.90-4.03(2H，m)、4.28-4.36(1H，m)、6.97(2H，td、J＝8.2，1.9Hz)、7.07-7.10(3H，m)、8.00(1H，d，J＝4.7Hz)、8.30(1H，s)

MS(ESI ⁺)：386[M+H] ⁺

The HPLC hold-time: 8.40 minutes

Embodiment 43

[2-(4-carboxyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

Add 20% palladium hydroxide catalyzer (7.2mg) in the methyl alcohol-THF solution (10mL-5mL) of [2-(4-methoxycarbonyl benzyl) the phenyl]-5a-carbon-β-D-glucopyranoside (72.0mg, 0.1mmol) that in embodiment 31, obtains.In nitrogen atmosphere, stir after 15 hours, catalyzer is filtered.The solvent underpressure distillation is removed, obtain title compound (38.2mg, 100%).

¹H-NMR(CD ₃OD)δ：0.86-1.00(1H，m)、1.51-1.58(1H，m)、2.01-2.11(1H，m)、3.16-3.34(2H，m)、3.43-3.50(2H，m)、3.67-3.73(1H，m)、3.95-4.88(3H，m)、6.87(1H，t，J＝13.5Hz)、7.03(1H，d，J＝7.4Hz)、7.12-7.21(2H，m)、7.30(2H，d，J＝8.1Hz)、7.88(2H，d，J＝8.1Hz)

MS(ESI ⁺)：389[M+H] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 44

[2-(4-vinyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

1) 2-(4-bromobenzyl) phenol is synthetic

In nitrogen gas stream, under ice-cold, (add dimethyl thioether (1.83mL among the 1.0g, dichloromethane solution 2.83mmol) (30.0mL) to 1-benzyloxy-2-(4-bromobenzyl) benzene, 42.46mmol) and the boron trifluoride diethyl etherate coordination compound (0.9mL, 7.07mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 19 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (527mg, 70.8%).

¹H-NMR(CDCl ₃)δ：3.92(2H，s)、4.62(1H，s)、6.73-6.76(1H，m)、6.85-6.99(1H，m)、7.06-7.14(4H，m)、7.35-7.40(2H，m)

2) trifluoromethanesulfonic acid (1S, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl synthetic

To (1S, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) hexalin (adds pyridine (205 μ L among the 300mg, dichloromethane solution 0.557mmol) (5.5mL), 2.53mmol), be cooled to 0 ℃ after, add trifluoromethanesulfanhydride anhydride (210 μ L, 1.25mmol).Under uniform temp, stir after 1 hour, add saturated sodium bicarbonate aqueous solution, use dichloromethane extraction.The organic layer that merges with saturated aqueous potassium hydrogen sulfate and saturated common salt water washing, is used dried over mgso.The solvent distillation is removed, obtain crude product (380mg).

¹H-NMR(CDCl ₃)δ：1.83(1H，dd，J＝15.9，14.0Hz)、2.00-2.14(2H，m)、3.39(1H，dd，J＝9.2，2.3Hz)、3.50(1H，dd，J＝9.6，2.6Hz)、3.56(1H，dd，J＝10.2，9.3Hz)、3.75(1H，dd，J＝9.2，3.4Hz)、3.86(1H，dd，J＝9.5，9.3Hz)、4.40(2H、s)、4.50(1H，d，J＝10.8Hz)、4.62(1H，d，J＝11.4Hz)、4.79(1H，d，J＝10.7Hz)、4.82(1H，d，J＝11.5Hz)、4.89(1H，d，J＝10.7Hz)、4.92(1H，d，J＝10.7Hz)、5.33(1H，br)、7.15-7.30(20H，m)

3) [2-(4-bromobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, DMF (1mL) solution of 1-benzyloxy-2-(4-bromobenzyl) benzene (386mg, 1.46mmol) is cooled off with ice bath, add NaH (60%, 52mg).Under uniform temp, stir after 10 minutes, with this reaction mixture under-40 ℃, be added drop-wise to trifluoromethanesulfonic acid (1S, 2R, 3S, 4R, 5R)-2,3, (655mg is in DMF 0.97mmol) (2.5mL) suspension for 4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl.Under uniform temp, stirred 2 minutes, stirred 30 minutes down, after stirring 1 hour under 0 ℃, add saturated aqueous common salt and water again at-40 ℃～0 ℃.Use extracted with diethyl ether, after organic layer water and saturated common salt water washing, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) carry out slightly refiningly, obtain crude product (200mg).In nitrogen gas stream, the crude product that obtains is dissolved in the methylene dichloride (2.5mL).Ice-cold add down dimethyl thioether (0.6mL, 13.48mmol) and the boron trifluoride diethyl etherate coordination compound (284 μ l, 2.2mmol).Make reaction solution slowly rise to room temperature on one side,, use dichloromethane extraction Yi Bian after stirring 25 hours, under ice-cold, add entry.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (10: 1)) make with extra care, obtain title compound (40.0mg, 42.9%).

¹H-NMR(CD ₃OD)δ：0.85(1H，q，J＝13.2，J＝11.1Hz)、1.44-1.59(1H，m)、2.03-2.09(1H，m)、3.13(1H，d，J＝8.7Hz)、3.19(1H，d，J＝5.1Hz)、3.23-3.26(2H，m)、3.37-3.45(2H，m)、3.63-3.68(1H，dd，J＝10.6，3.9Hz)、3.81(1H，d，J＝14.4Hz)、4.10(1H，d，J＝14.4Hz)、4.09-4.18(1H，m)、6.79(1H，t，J＝7.5Hz)、6.96(1H，d，J＝9.0Hz)、7.03-7.13(4H，m)、7.27-7.32(2H，m)

4) 2-(4-vinyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen gas stream, with [2-(4-bromobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside (40mg, 0.094mmol) be dissolved in the toluene (2mL), to wherein adding tributylvinyl tin (36mg, 0.11mmol), tetrakis triphenylphosphine palladium (0) (2.7mg), 2, the 6-di-tert-butyl-4-methy phenol (1.5mg, 0.007mmol) after, it was refluxed 15 hours.Reaction solution is cooled to room temperature, and underpressure distillation removes and desolvates.With the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (9mg, 25.7%).

¹H-NMR(CD ₃OD)δ：0.86(1H，q，J＝12.0，11.7)、1.42-1.55(1H，m)、1.96-2.03(1H，m)、3.10-3.19(2H，m)、3.22-3.25(2H，m)、3.36-3.44(2H，m)、3.63(1H，dd，J＝10.6，4.1Hz)、3.81-4.08(2H，m)、4.09-4.16(1H，m)、5.07(1H，dd，J＝11.0，1.2Hz)、5.63(1H，dd，J＝18.0，1.2Hz)、6.61(1H，dd，J＝18.0，11.0Hz)、6.78(1H，t，J＝7.3Hz)、7.03(1H，d，J＝6.3Hz)、7.02-7.24(6H，m)

MS(ESI ⁺)：370[M] ⁺

The HPLC hold-time: 11.8 minutes

Embodiment 45

2-[4-(2,2-difluoroethylene base) benzyl] phenyl }-5a-carbon-β-D-glucopyranoside

1) synthesizing in nitrogen gas stream of 1-diethoxymethyl-4-(2,2-difluoroethylene base) benzene, to ice bath chilled Diisopropylamine (3.40mL, drip in 24.2mmol) n-Butyl Lithium hexane solution (2.44M, 9.94mL) after, add THF (20mL).The solution that obtains is cooled to-78 ℃, to wherein drip diethyl (difluoromethyl) phosphonic acid ester (3.62mL, 23.1mmol).Under uniform temp, stir after 5 minutes, and dropping terephthalaldehyde list (diethyl) acetal (terephthalaldehyde monodiethylacetal) (4.2mL, 21.0mmol).Reaction mixture was stirred 50 minutes under uniform temp, at room temperature stirred 20 minutes, stirred 34 hours down at 70 ℃～75 ℃ again.After being cooled to room temperature, add saturated aqueous ammonium chloride and water, use extracted with diethyl ether.Organic layer is washed with saturated aqueous ammonium chloride, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 20)) make with extra care, obtain title compound (1.10g, 22%).

¹H-NMR(CDCl ₃)δ：1.24(6H，t，J＝7.1Hz)、3.45-3.68(4H，m)、5.27(1H，dd，J＝26.4，3.8Hz)、5.49(1H，s)、7.32(2H，d，J＝8.4Hz)、7.44(2H，d，J＝8.4Hz)

2) 4-(2,2-difluoroethylene base) phenyl aldehyde is synthetic

In nitrogen gas stream, to using the chilled 1-diethoxymethyl-4-(2 of ice bath, 2-difluoroethylene base) benzene (998.1mg, 4.12mmol) ether (4mL) solution in add 2M aqueous hydrochloric acid (2.5mL), reaction mixture was stirred 3 minutes under uniform temp, at room temperature stirred again 3.75 hours.Use extracted with diethyl ether, after organic layer usefulness saturated sodium bicarbonate aqueous solution and saturated common salt water washing, use dried over sodium sulfate.Underpressure distillation removes and desolvates, and obtains crude product.

¹H-NMR(CDCl ₃)δ：5.37(1H，dd，J＝25.7，3.5Hz)、7.49(2H，d，J＝8.4Hz)、7.85(2H，d，J＝8.4Hz)、9.98(1H，s)

3) synthesizing of (2-benzyloxy phenyl)-[4-(2,2-difluoroethylene base) phenyl] methyl alcohol

In nitrogen gas stream, with 2-benzyloxy bromobenzene (1.63g, THF 6.18mmol) (4mL) solution is cooled to-78 ℃, drip n-Butyl Lithium hexane solution (2.44M, 2.66mL).Under uniform temp, stir after 25 minutes, drip THF (1mL) solution of thick 4-(2, the 2-difluoroethylene base) phenyl aldehyde that originally obtained.Under uniform temp, stir after 1.25 hours, add saturated aqueous ammonium chloride and water.Use extracted with diethyl ether, after organic layer is washed with saturated aqueous ammonium chloride, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (1.17g, 81%).

¹H-NMR(CDCl ₃)δ：2.94(1H，d，J＝6.1Hz)、4.98-5.04(2H，m)、5.26(1H，dd，J＝26.4，3.8Hz)、6.03(1H，d，J＝6.1Hz)、6.88-7.04(2H，m)、7.14-7.38(11H，m)

4) 1-benzyloxy-2-[4-(2,2-difluoroethylene base) benzyl] benzene synthetic

In nitrogen gas stream, with (2-benzyloxy phenyl)-[4-(2,2-difluoroethylene base) phenyl] methyl alcohol (1.14g, methylene dichloride 3.24mmol) (10mL) solution is cooled to-78 ℃, add triethyl silicane (5.17mL, 32.35mmol).(0.49mL 3.88mmol), stirs reaction mixture 5 minutes down at-78 ℃, stirs 10 minutes down ice-cold again to spend 5 minutes dropping boron trifluoride diethyl etherate coordination compoundes.Add saturated sodium bicarbonate aqueous solution and water, use dichloromethane extraction.With organic layer saturated common salt water washing, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 30)) make with extra care, obtain title compound (984.5mg, 90%).

¹H-NMR(CDCl ₃)δ：4.00(2H，s)、5.05(2H，s)、5.23(1H，dd，J＝26.2，3.8Hz)、6.85-6.95(2H，m)、7.05-7.40(11H，m)

5) 2-[4-(2,2-difluoroethylene base) benzyl] phenol synthetic

In nitrogen gas stream, with 1-benzyloxy-2-[4-(2,2-difluoroethylene base) benzyl] and benzene (984.5mg, methylene dichloride 2.93mmol) (12mL) solution is cooled to-78 ℃, the dichloromethane solution of dropping boron tribromide-dimethyl thioether (1.0M, 7.32mL).Under uniform temp, stirred 10 minutes, after 2 hours, drip the dichloromethane solution (4.39mL) of boron tribromide-dimethyl thioether in ice-cold stirring down more again.Under uniform temp, stir after 3.5 hours, add aqueous sodium hydroxide solution and sodium bicarbonate aqueous solution.Use dichloromethane extraction,, use dried over sodium sulfate organic layer saturated common salt water washing.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 7)) make with extra care, obtain title compound (647.5mg, 90%).

¹H-NMR(CDCl ₃)δ：3.98(2H，s)、4.62(1H，s)、5.24(1H，dd，J＝26.2，3.8Hz)、6.78(1H，d，J＝8.1Hz)、6.84-6.94(1H，m)、7.04-7.32(6H，m)

6) { 2-[4-(2,2-difluoroethylene base) benzyl] phenyl }-5a-carbon-β-D-glucopyranoside synthetic

In nitrogen gas stream, with 2-[4-(2,2-difluoroethylene base) benzyl] phenol (80mg, DMF 0.324mmol) (1mL) solution places ice bath to cool off, to wherein add NaH (60%, 13mg).Under uniform temp, stir after 10 minutes, under-40 ℃, this reaction mixture is added drop-wise to trifluoromethanesulfonic acid (1S, 2R, 3S, 4R, 5R)-2,3, (181mg is in DMF 0.270mmol) (2.5mL) suspension for 4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl.Under uniform temp, stirred 2 minutes, stirred 30 minutes down, after stirring 1 hour under 0 ℃, add saturated aqueous common salt and water again at-40 ℃～0 ℃.Use extracted with diethyl ether, after organic layer water and saturated common salt water washing, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 7)) make with extra care, obtain object (180.7mg).In nitrogen gas stream, (188mg 1.27mmol) mixes, and is dissolved in the methylene dichloride (2.5mL) with penta-methyl benzene with this product 65mg (0.0848mmol).After being cooled to-78 ℃, and the dichloromethane solution of dropping boron trichloride (1.0M, 0.42mL).Reaction mixture after stirring 2.25 hours under the uniform temp, is dripped methyl alcohol (0.5mL).Under uniform temp, drip sodium methylate methanol solution (1M, 1.26mL) after, at room temperature stirred 15 minutes.After mixture filtered, filtrate decompression is concentrated, with the residue that obtains with preparing TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (22.1mg, 64%).

¹H-NMR(CD ₃OD)δ：0.82-1.04(1H，m)、1.44-1.64(1H，m)、1.98-2.12(1H，m)、3.12-3.28(2H，m)、3.40-3.54(2H，m)、3.69(1H，dd，J＝10.7，4.0Hz)、3.89(1H，d，J＝14.8Hz)、4.02(1H，d，J＝14.8Hz)、4.10-4.26(1H，m)、5.40(1H，dd，J＝27.0，4.0Hz)、6.78-6.90(1H，m)、6.96-7.30(7H，m)

MS(ESI ⁺)：406[M] ⁺

The HPLC hold-time: 18.51 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Moving phase: according to from 10mM AcONH ₄/ H ₂O (95%)+10mM AcONH ₄/ MeOH (5%) is to 10mM AcONH ₄The concentration gradient that/MeOH (100%) spends 20 minutes is carried out, then at the same terms (10mM AcONH ₄/ MeOH (100%)) wash-out is 5 minutes under.

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 46-58

Use corresponding starting raw material and reagent, similarly operate, obtain the purpose compound with the foregoing description.

Embodiment 46

[2-(2,3-Dihydrobenzofuranes-5-ylmethyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.93(1H，q，J＝13.2Hz，J＝11.4Hz)、1.49-1.58(1H，m)、2.01-2.07(1H，dt，J＝13.2，4.5Hz)、3.12(1H，t，J＝8.4Hz)、3.20(1H，d，J＝9.3Hz)、3.25(1H，d，J＝4.8Hz)、3.30-3.53(2H，m)、3.69(1H，dd，J＝6.6，4.2Hz)、3.85(1H，d，J＝15Hz)、3.91(1H，d，J＝15Hz)、4.13-4.21(1H，m)、4.47(2H，t，J＝8.7Hz)、6.59(1H，d，J＝8.4Hz)、6.83(1H，t，J＝7.2Hz)、6.89(1H，d，J＝8.1Hz)、6.99-7.15(4H，m)

MS(ESI ⁺)：386[M] ⁺

The HPLC hold-time: 10.5 minutes

Embodiment 47

[2-(3-fluoro-4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.99(1H，q，J＝12.6Hz)、1.48-1.59(1H，m)、2.04-2.10(1H，dt，J＝13.2，4.2Hz)、2.18(3H，s)、3.18-3.32(2H，m)、3.44-3.51(2H，m)、3.68(1H，dd，J＝6.9，3.9Hz)、3.89(1H，d，J＝15Hz)、3.97(1H，d，J＝15Hz)、4.14-4.22(1H，m)、6.81-6.90(3H，m)、7.00-7.17(4H，m)

MS(ESI ⁺)：376.4[M] ⁺

The HPLC hold-time: 11.7 minutes

Embodiment 48

[2-(4-methoxyl group-3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.94(1H，q，J＝12.9，11.7Hz)、1.47-1.57(1H，m)、2.01-2.08(1H，dt，J＝13.2，4.2Hz)、2.12(3H，s)、3.18-3.34(2H，m)、3.45-3.52(2H，m)、3.68(1H，dd，J＝6.6，4.2Hz)、3.75(3H，s)、?3.84(1H，d，J＝14.7Hz)、3.90(1H，d，J＝14.7Hz)、4.14-4.21(1H，m)、6.76(1H，d，J＝8.7Hz)、6.83(1H，t，J＝7.5Hz)、6.95-7.15(5H，m)

MS(ESI ⁺)：389[M+H] ⁺

The HPLC hold-time: 11.5 minutes

Embodiment 49

[2-(4-pyrazol-1-yl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.95(1H，q，J＝12.9，11.4Hz)、1.49-1.59(1H，m)、2.02-2.09(1H，dt，J＝12.3，4.2Hz)、3.20(1H，d，J＝9.0Hz)、3.23(1H，d，J＝6.3Hz)、3.43-3.53(2H，m)、3.67(1H，dd，J＝6.6，4.2Hz)、3.98(1H，d，J＝14.7Hz)、4.07(1H，d，J＝15Hz)、4.16-4.24(1H，m)、6.49(1H，s)、6.87(1H，t，J＝7.5Hz)、7.05(1H，d，J＝8.1Hz)、7.14(2H，d，J＝7.5Hz)、7.35(2H，d，J＝8.4Hz)、7.56(2H，d，J＝8.4Hz)、7.68(1H，s)、8.12(1H，s)

MS(ESI ⁺)：411[M+H] ⁺

The HPLC hold-time: 10.5 minutes

Embodiment 50

[2-(3-chloro-4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.94(1H，dd，J＝24.4，13.2Hz)、1.5-1.65(1H，m)、2.05(1H，dt，J＝13.5，4.1Hz)、3.18-3.35(2H，m)、3.43-3.55(2H，m)、3.70(1H，dd，J＝10.7，4.1Hz)、3.82(3H，s)、3.82(1H，d，J＝14.8Hz)、3.97(1H，d，J＝14.8Hz)、4.15-4.25(1H，m)、6.86(1H，td，J＝7.4，1.1Hz)、6.92(1H，d，J＝8.2Hz)、7.0-7.2(5H，m)

MS(ESI ⁺)：409[M+H] ⁺、431[M+Na] ⁺

The HPLC hold-time: 11.25 minutes

Embodiment 51

[2-(3, the 4-methylenedioxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：1.01(1H，q，J＝12.7Hz)、1.45-1.64(1H，m)、2.04-2.13(1H，m)、3.19-3.35(4H，m)、3.46-3.54(2H，m)、3.69-3.74(1H，m)、3.89(2H，q，J＝16.1)，4.15-4.22(1H，m)、5.86(2H，s)，6.68(3H，s)、6.85(1H，t、J＝6.1Hz)、7.00-7.18(3H，m)

MS(ESI ⁺)：389[M+H] ⁺

The HPLC hold-time: 10.6 minutes

Embodiment 52

[2-(4-cyclobutyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.81-0.96(1H，m)、1.45-1.61(1H，m)、1.78-2.37(7H，m)、3.15-3.34(5H，m)、3.40-3.55(2H，m)、3.66-4.76(1H，m)、3.95(2H，q、J＝13.7Hz)、4.13-4.24(1H，m)、6.87(1H，t、J＝8.1Hz)、6.97-7.17(7H、m)

MS(ESI ⁺)：425[M+Na] ⁺

The HPLC hold-time: 13.6 minutes

Embodiment 53

[2-(4-ethanoyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.84-0.98(1H，m)、1.50-1.56(1H，m)、2.00-2.08(1H，m)、2.55(3H，s)、3.15-3.32(3H，m)、3.42-3.50(2H，m)、3.65-3.70(1H，m)、3.94-4.24(3H，m)、4.89(2H，s)、6.86(1H，t、J＝7.3Hz)、7.03(1H，d，J＝8.1Hz)、7.12-7.20(2H、m)、7.34(2H，d，J＝8.1Hz)、7.86(2H，d，J＝8.1Hz)

MS(ESI ⁺)：386[M+1] ⁺

The HPLC hold-time: 9.8 minutes

Embodiment 54

[2-(4-methoxy-benzyl)-5-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：0.92-1.06(1H，m)、1.51-1.66(1H，m)，2.08(1H，dt，J＝13.2，4.0Hz)、2.32(3H，s)、3.21-3.40(2H，m)、3.47-3.56(2H，m)、3.71-3.78(1H，m)、3.77(3H，s)、3.84(1H，d，J＝14.2Hz)，3.95(1H，d，J＝14.2Hz)、4.14-4.26(1H，m)、6.68-6.72(1H，m)、6.78-6.85(2H，m)、6.86-6.91(1H，m)、6.97(1H，d，J＝7.8Hz)、7.10-7.16(2H，m)

MS(ESI ⁺)：388[M] ⁺

The HPLC hold-time: 11.26 minutes

Embodiment 55

[2-(4-Ethylbenzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：1.20(1H，t，J＝7.6Hz)、1.40-1.80(1H，m)、2.04-2.09(1H，m)、2.59(2H，q，J＝7.58Hz)、3.19-3.55(5H，m)、3.88-3.96(1H，m)、3.99(2H，m)、6.89(2H，d，J＝5.4Hz)、7.06-7.15(5H，m)

MS(ESI ⁺)：378[M] ⁺

The HPLC hold-time: 11.9 minutes

Embodiment 56

[(thionaphthene-2-yl) aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside

¹H-NMR(CD ₃OD)δ：1.04(1H，m)、1.40-1.80(1H，m)、2.08-2.16(1H，m)、3.14-3.67(5H，m)、4.14(1H，d，J＝15.7Hz)、4.19-4.27(1H，m)、4.36(1H，d，J＝15.5Hz)、6.89(1H，dd、J＝8.1，6.6Hz)、7.02(1H，s)、7.07(1H，d，J＝8.1Hz)、7.17-7.28(4H，m)、7.63(1H，d，J＝7.6Hz)、7.71(1H，d，J＝7.6Hz)

MS(ESI ⁺)：400[M] ⁺

The HPLC hold-time: 12.0 minutes

Embodiment 57

2-[1-(4-cyclopropyl phenyl) ethyl] phenyl }-5a-carbon-β-D-glucopyranoside

(with preparation TLC (developping solution: methyl alcohol: the isomer of isolating, low polarity one side methylene dichloride=1: 10))

¹H-NMR(CD ₃OD)δ：0.40(1H，dd，J＝9.3，9.0Hz)、0.56-0.66(2H，m)、0.84-0.96(2H，m)、1.36-1.54(1H，m)、1.52(3H，d，J＝6.6Hz)、1.76-1.88(2H，m)、3.04-3.12(1H，dd，J＝10.8，9.9Hz)、3.25(1H，t，J＝10.8Hz)、3.26-3.40(1H，m)、3.42(1H，t，J＝9.9Hz)、3.64(1H，dd，J＝10.4，4.8Hz)、4.08-4.22(1H，m)、4.50(1H，dd，J＝12.0，6.3Hz)、6.84-6.99(4H，m)、6.99-7.06(2H，m)、7.06-7.28(1H，m)、7.20-7.26(1H，m)

MS(ESI ⁺)：399[M+H] ⁺

The HPLC hold-time: 12.7 minutes

Embodiment 58

2-[1-(4-cyclopropyl phenyl) ethyl] phenyl }-5a-carbon-β-D-glucopyranoside

(with preparation TLC (developping solution: methyl alcohol: the isomer of isolating, high polarity one side methylene dichloride=1: 10))

¹H-NMR(CD ₃OD)δ：0.56-0.66(2H，m)、0.84-0.96(2H，m)、1.10(1H，dd，J＝9.6，9.0Hz)、1.44-1.64(1H，m)、1.53(3H，d，J＝6.6Hz)、1.76-1.88(1H，m)、2.13(1H，ddd，J＝12.2，4.5，3.3Hz)、3.20-3.28(2H，m)、3.44(1H，t，J＝10.5Hz)、3.53(1H，dd，J＝11.4，6.6Hz)、3.73(1H，dd，J＝11.4，2.4Hz)、4.06-4.22(1H，m)、4.50(1H，dd，J＝12.0，6.3Hz)、6.82-7.03(4H，m)、7.06-7.16(4H，m)

MS(ESI ⁺)：399[M+H] ⁺

The HPLC hold-time: 12.7 minutes

Embodiment 59

[2-(4-cyclopropyl benzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside

1) synthesizing of (4-cyclopropyl phenyl)-(3-methoxyl group-5-thiotolene-2-yl) ketone

In nitrogen atmosphere, to the THF solution (20mL) of embodiment 38 same synthetic (4-cyclopropyl phenyl)-(3-methoxythiophene-2-yl) ketones (1.05g, 4.06mmol) in add methyl-iodide (2.53mL, 40.6mmol).This solution is cooled to-78 ℃, spends the heptane-THF-ethylbenzene solution (2.0M, 2.44mL, 4.88mmol) that added LDA in 20 minutes.Under uniform temp, stirred 3 hours.Spend the heptane-THF-ethylbenzene solution (2.0M, 2.44mL, 4.88mmol) that added LDA in 20 minutes in this solution of clockwise again, stirred 2 hours, add saturated ammonium chloride solution.Use ethyl acetate extraction, with organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (589mg, 53%).

¹H-NMR(CDCl ₃)δ：0.74-0.80(2H，m)、1.00-1.06(2H，m)、1.91-1.97(1H，m)、2.49(3H，s)、3.81(3H，s)、6.62(1H，s)、7.08(2H，d，J＝7.9Hz)、7.68(2H，d，J＝8.3Hz)

2) synthesizing of (4-cyclopropyl phenyl)-(3-hydroxy-5-methyl base thiophene-2-yl) ketone

In nitrogen gas stream, under-15 ℃, (add the dichloromethane solution (1.0M, 6.4mL, 6.4mmol) of boron trichloride among the 582mg, dichloromethane solution 2.14mmol) (12mL), stirred 1 hour to (4-cyclopropyl phenyl)-(3-methoxyl group-5-thiotolene-2-yl) ketone.Add entry, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methyl alcohol: methylene dichloride (1: 100)) make with extra care, obtain title compound (497mg, 90%).

¹H-NMR(CDCl ₃)δ：0.76-0.82(2H，m)、1.03-1.10(2H，m)、1.93-1.98(1H，m)、2.49(3H，s)、6.57(1H，s)、7.15(2H，d，J＝8.4Hz)、7.85(2H，d，J＝8.4Hz)、12.80(1H，s)

3) (4-cyclopropyl phenyl)-[5-methyl-3-((1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy) thiophene-2-yl] ketone synthetic

In nitrogen gas stream, under ice-cold, to (4-cyclopropyl phenyl)-(3-hydroxy-5-methyl base thiophene-2-yl) ketone (360mg, 1.39mmol), (1S, 2S, 3S, 4R, 5R)-2,3, drip diisopropyl azo-2-carboxylic acid (0.27mL, 1.39mmol) in the mixture of 4-three benzyloxies-5-benzyloxymethyl hexalin (500mg, 0.93mmol), triphenylphosphine (365mg, 1.39mmol) and toluene (3.1mL).After at room temperature stirring 15 hours, underpressure distillation removes desolvates, with the residue that obtains with silica gel flash distillation column chromatography (developping solution=normal hexane: ethyl acetate (4: 1)) make with extra care, obtain title compound (237mg, 33%).

¹H-NMR(CDCl ₃)δ：0.70-0.73(2H，m)、0.99-1.02(2H，m)、1.35-1.50(1H，m)、1.64-1.72(1H，m)、1.87-1.94(1H，m)、2.07-2.14(1H，m)、2.44(3H，s)、3.36-3.56(5H，m)、4.07-4.13(1H，m)、4.33-4.88(8H，m)、6.61(1H，s)、7.01(2H，d，J＝7.9Hz)、7.05-7.35(22H，m)、7.62(2H，d，J＝8.2Hz)

4) 2-(4-cyclopropyl benzyl)-5-methyl-3-[(1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyloxy] thiophene synthetic

In nitrogen atmosphere, under ice-cold, to (4-cyclopropyl phenyl)-[5-methyl-3-((1R, 2S, 3S, 4R, 5R)-2,3, thiophene-2-yl 4-three benzyloxies-5-benzyloxymethyl cyclohexyloxy)] add chlorine trimethyl silane (0.46mL, 3.65mmol), hydrogenation cyano group boron sodium (230mg in acetonitrile (5mL) solution of ketone (237mg, 0.30mmol), 3.65mmol), stirred 1 hour down at 0 ℃.Add methylene dichloride, use diatomite filtration, the filtrate decompression distillation is removed.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain title compound (135mg, 58%).

¹H-NMR(CDCl ₃)δ：0.58-0.65(2H，m)、0.86-0.94(2H，m)、1.23-1.28(1H，m)、1.57-1.65(1H，m)、1.77-1.86(1H，m)、2.06-2.12(1H，m)、2.33(3H，s)、3.43-3.65(5H，m)、3.93(2H，s)、3.98-4.08(1H，m)、4.44(2H，s)、4.51(1H，d，J＝10.8Hz)、4.75-4.97(5H，m)、6.55(1H，s)、6.92(2H，d，J＝8.1Hz)、7.10(2H，d，J＝8.1Hz)、7.18-7.37(20H，m)

5) [2-(4-cyclopropyl benzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside is synthetic

In nitrogen gas stream, under-78 ℃, to 2-(4-cyclopropyl benzyl)-5-methyl-3-[(1R, 2S, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl cyclohexyloxy)] thiophene (134mg, 0.18mmol) dichloromethane solution (6mL) in add the dichloromethane solution (1.0M, 0.88mL, 0.88mmol) of penta-methyl benzene (390mg, 2.63mmol), boron trichloride, stirred 1 hour down at-78 ℃.Add methyl alcohol, with the reaction solution concentrating under reduced pressure.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (20: 1)) make with extra care, obtain title compound (35mg, 49%).

¹H-NMR(CD ₃OD)δ：0.62-0.68(2H，m)、0.90-0.97(2H，m)、1.10-1.21(1H，m)、1.43-1.56(1H，m)、1.82-1.95(1H，m)、2.03-2.11(1H，m)、2.36(3H，s)、3.25-3.90(6H，m)、3.94(2H，m)、6.63(1H，m)、6.98(2H，d、J＝8.4Hz)、7.11(2H，d、J＝7.9Hz)

MS(ESI ^-)：403[M-H] ^-

Embodiment 60

[2-(4-Ethylbenzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside

Use corresponding starting raw material and reagent, similarly operate, obtain the purpose compound with embodiment 59.

¹H-NMR(CD ₃OD)δ：1.10-1.22(4H，m)、1.40-1.54(1H，m)、2.02-2.09(1H，m)、2.33(3H，s)、2.58(2H，d、J＝7.6Hz)3.22-3.25(2H，m)、?3.28-3.35(2H，m)、3.39-3.45(1H，m)、3.52(1H，dd、J＝10.7，6.2Hz)、3.71(1H，dd、J＝10.7，4.0Hz)、3.83-3.90(1H，m)、6.60(1H，s)、7.06(2H，d、J＝8.2Hz)、7.11(2H，d、J＝8.2Hz)

MS(ESI ⁺)：393[M+H] ⁺、415[M+Na] ⁺

Embodiment 61

[5-chloro-2-(4-cyclopropyl benzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside

1) 4-cyclopropyl-N-methoxyl group-N-methyl-benzamide is synthetic

In nitrogen gas stream, under-78 ℃, spend 15 minutes clockwise 1-bromo-4-cyclopropyl-phenyl (1.8g, 9.13mmol) anhydrous THF solution (30mL) in drip the hexane solution (1.6M, 6.0mL, 9.59mmol) of n-Butyl Lithium.Under-78 ℃,, drip N, N '-dimethoxy-N, the THF solution (5mL) of N '-dimethyl urea (1.42g, 9.59mmol) with this solution stirring 10 minutes.At room temperature stirred 30 minutes.Add saturated aqueous ammonium chloride, use extracted with diethyl ether, the organic layer anhydrous magnesium sulfate drying.After the filtration, underpressure distillation removes desolvates, with the residue that obtains with silica gel column chromatography (developping solution=normal hexane: ethyl acetate (4: 1)) make with extra care, obtain title compound (875mg, 95%).

¹H-NMR(CDCl ₃)δ：0.73-0.78(2H，m)、0.97-1.03(2H，m)、1.87-1.94(1H，m)、3.34(3H，s)、3.56(3H，s)、7.08(2H，d、J＝8.3Hz)、7.60(2H，d、J＝8.3Hz)

2) (5-chloro-3-methoxythiophene-2-yl)-(4-cyclopropyl phenyl) ketone is synthetic

In nitrogen gas stream, under-78 ℃, to according to document (J.Or g.Chem., 58,4629-4633 (1993)) drips the hexane solution (1.6M, 2.43mL, 3.88mmol) of n-Butyl Lithium in the anhydrous THF solution (15mL) of the method synthetic 2-bromo-5-chloro-3-methoxythiophene (882mg, 3.88mmol) of record.Under-78 ℃,, drip the THF solution (3mL) of 4-cyclopropyl-N-methoxyl group-N-methyl-benzamide (875mg, 4.26mmol) with this solution stirring 10 minutes.Under-78 ℃, reaction solution was stirred 30 minutes.To wherein adding saturated aqueous ammonium chloride, use ethyl acetate extraction, with the organic layer anhydrous magnesium sulfate drying.After the filtration, underpressure distillation removes desolvates, with the residue that obtains with silica gel column chromatography (developping solution=normal hexane: ethyl acetate (4: 1)) make with extra care, obtain title compound (714mg, 63%).

¹H-NMR(CDCl ₃)δ：0.75-0.81(2H，m)、1.02-1.08(2H，m)、1.92-1.98?(1H，m)、3.80(3H，s)、6.78(1H，s)、7.10(2H，d、J＝8.3Hz)、7.68(2H，d、J＝8.3Hz)

3) [5-chloro-2-(4-cyclopropyl benzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside is synthetic

Use and synthetic (5-chloro-3-methoxythiophene-2-yl)-(4-cyclopropyl-phenyl) ketone reagent corresponding, similarly operate, obtain the purpose compound with embodiment 59.

¹H-NMR(CD ₃OD)δ：0.63-0.66(2H，m)、0.88-0.93(2H，m)、1.15-1.21(1H，m)、1.61-1.67(1H，m)、1.82-1.87(1H，m)、1.99-2.03(1H，m)、3.22-3.57(4H，m)、3.70-3.74(1H，m)、3.87-3.91(1H，m)、3.92(2H，s)、6.86(1H，s)、6.97(2H，d、J＝8.1Hz)、7.09(2H，d、J＝8.1Hz)

MS(ESI ⁺)：425[M+H] ⁺

Embodiment 62

(1R, 2S, 3R, 6R)-6-[2-(4-cyclopropyl benzyl) phenoxy group]-4-(methylol) hexamethylene-4-alkene-1,2, the 3-triol

1) 1-(4-cyclopropyl phenyl) methyl-2-[(1R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-2-alkene oxygen base] benzene synthetic

In nitrogen gas stream, under ice-cold, to document (J.Or g.Chem., 63,5668-5671 (1998)) Ji Zai (1S, 4R, 5S, 6S)-4,5,6-three (benzyloxy)-3-(benzyloxymethyl) hexamethylene-2-enol (adds 2-(4-cyclopropyl benzyl) phenol (31mg among the 51mg, toluene solution 0.095mmol) (300 μ L), 0.14mmol) and tributylphosphine (70 μ L, 0.28mmol) after, under uniform temp, add tetramethyl-azodicarboxy acid amides (48mg, 0.28mmol).Under uniform temp, stir after 20 hours, add hexane, remove by filter throw out, the solvent distillation of filtrate is removed.With the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 5)) make with extra care, obtain title compound (44mg, 62%).

¹H-NMR(CDCl ₃)δ：0.54(2H，m)、0.84(2H，m)、1.75(1H，m)、3.82-3.92(3H，m)、3.93(2H，s)、4.19(1H，d，J＝12.5Hz)、4.35(1H，br)、4.41(1H，d，J＝11.7Hz)、4.46(1H，d，J＝11.8Hz)、4.61(1H，d，J＝10.7Hz)、4.68(1H，d，J＝10.2Hz)、4.72(1H，d，J＝10.5Hz)、4.79(1H，d，J＝10.8Hz)、4.85(1H，d，J＝10.7Hz)、4.99(1H，d，J＝11.0Hz)、5.04(1H，br)、?5.65(1H，s)、6.8-7.4(28H，m)

2) (1R, 2S, 3R, 6R)-6-[2-(4-cyclopropyl benzyl) phenoxy group]-4-(methylol) hexamethylene-4-alkene-1,2,3-triol synthetic

In nitrogen gas stream, under-78 ℃, to 1-(4-cyclopropyl phenyl) methyl-2-[(1R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-2-alkene oxygen base] benzene (12mg, 0.016mmol) and penta-methyl benzene (24mg, 0.17mmol) dichloromethane solution (300 μ L) in add the 1.0M dichloromethane solution of boron trichloride (160 μ L 0.16mmol), stirred 1.5 hours under uniform temp.After adding methyl alcohol, be warming up to room temperature, underpressure distillation removes and desolvates.With the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 8)) make with extra care, obtain title compound (4.1mg, 70%).

¹H-NMR(CD ₃OD)δ：0.61(2H，m)、0.89(2H，m)、1.83(1H，m)、3.55(1H，dd，J＝10.5，7.8Hz)、3.72(1H，dd，J＝10.5，7.8Hz)、3.89(1H，d，J＝14.8Hz)、3.93(1H，d，J＝14.9Hz)、4.11(2H，brs)、4.15(1H，d，J＝7.8Hz)、4.80(1H，d，J＝7.6Hz)、5.60(1H，t，J＝1.5Hz)、6.84(1H，t，J＝7.3Hz)、6.93(2H，d，J＝8.1Hz)、7.06(1H，d，J＝8.2Hz)、6.97-7.18(3H，m)

MS(ESI ⁺)：405[M+Na] ⁺

The HPLC hold-time: 12.5 minutes

Embodiment 63

(1R, 2S, 3R, 6R)-and 4-methylol-6-[2-(4-methoxy-benzyl) phenoxy group] hexamethylene-4-alkene-1,2, the 3-triol

1) 1-(4-p-methoxy-phenyl) methyl-2-[(1R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-2-alkene oxygen base] benzene synthetic

In nitrogen gas stream, under ice-cold, to reference (Tetrahedron, 56,7109-7122 (2000)) synthetic (1S, 3S, 4S, 5R, 6S)-4,5,6-three benzyloxies-1-(benzyloxymethyl) hexamethylene-1, the 3-glycol (adds 2-(4-methoxy-benzyl) phenol (299mg among the 561mg, toluene solution 1.01mmol) (3mL), 1.40mmol) and tributylphosphine (380 μ L, 1.53mmol) after, under uniform temp, add tetramethyl-azodicarboxy acid amides (261mg, 1.52mmol).Under uniform temp, stir after 20 hours, add hexane, remove by filter throw out, the solvent distillation of filtrate is removed.With the residue that obtains with silica gel chromatography (developping solution=ethyl acetate: normal hexane (1: 7 → 1: 1)) make with extra care, obtain title compound (312mg, 42%).

¹H-NMR(CDCl ₃)δ：3.64(3H，s)、3.80-3.95(3H，m)、3.92(2H，s)、4.19(1H，d，J＝13.6Hz)、4.36(1H，br)、4.41(1H，d，J＝11.9Hz)、4.46(1H，d，J＝11.8Hz)、4.64(1H，d，J＝11.0Hz)、4.69(1H，d，J＝10.8Hz)、4.71(1H，d，J＝10.8Hz)、4.79(1H，d，J＝10.8Hz)、4.85(1H，d，J＝11.0Hz)、4.99(1H，d，J＝11.0Hz)、5.05(1H，br)、5.67(1H，s)、6.71(2H，d，J＝8.7Hz)、6.80-7.40(26H，m)

MS(ESI ⁺)：755[M+Na] ⁺

2) (1R, 2S, 3R, 6R)-and 4-methylol-6-[2-(4-methoxy-benzyl) phenoxy group] hexamethylene-4-alkene-1,2,3-triol synthetic

In nitrogen gas stream, under-78 ℃, to 1-(4-p-methoxy-phenyl) methyl-2-[(1R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-2-alkene oxygen base] benzene (1.0M dichloromethane solution (6.0mL that adds boron trichloride among the 312mg, dichloromethane solution 0.426mmol) (12mL), 6.0mmol), under uniform temp, stirred 1.5 hours.After adding methyl alcohol, be warming up to room temperature, underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methyl alcohol: methylene dichloride (1: 8)) make with extra care, obtain title compound (37.9mg, 24%).

¹H-NMR(CD ₃OD)δ：3.56(1H，dd，J＝10.5，8.0Hz)、3.73(1H，m)、3.73(3H，s)、3.88(1H，d，J＝14.9Hz)、3.92(1H，d，J＝14.9Hz)、4.11(2H，brs)、4.16(1H，m)、4.81(1H，m)、5.61(1H，t，J＝1.7Hz)、6.77(2H，d，J＝8.7Hz)、6.84(1H，t，J＝7.3Hz)、6.99(1H，d，J＝8.1Hz)、7.04(1H，d，J＝7.5Hz)、7.10(2H，d，J＝8.9Hz)、7.13(1H，m)

MS(ESI ⁺)：395[M+Na] ⁺

The HPLC hold-time: 10.8 minutes

Embodiment 64

(1R, 2S, 3S, 6R)-4-[3-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-4-alkene-1,2, the 3-triol

1) 3-(4-Ethylbenzyl) phenyl-boron dihydroxide is synthetic

In nitrogen gas stream, with 1-bromo-3-(4-Ethylbenzyl) benzene (2.19g, THF 7.96mmol) (20mL) solution is cooled to-78 ℃, drip n-Butyl Lithium hexane solution (2.44M, 3.42mL) after, under uniform temp, stirred 20 minutes.Add trimethyl borate (2.68mL, 23.87mmol) after, under uniform temp, stirred 5 minutes, at room temperature stirred 12.5 hours.After the ice bath cooling, drip concentrated hydrochloric acid (10mL), under uniform temp, stirred 1 hour.With the mixture extracted with diethyl ether, after organic layer washed with water, use dried over sodium sulfate.The solvent underpressure distillation is removed, in the white solid that obtains, add hexane-ethyl acetate (10: 1) (5mL), after the filtration, with hexane-ethyl acetate (10: 1) washing.With the white powder drying under reduced pressure that obtains, obtain title compound (604.2mg, 32%).

¹H-NMR(CDCl ₃)δ：1.22(3H，t，J＝7.6Hz)、2.62(2H，q，J＝7.6Hz)、4.07(2H，s)、7.10-7.20(4H，m)、7.36-7.44(2H，m)、8.00-8.10(2H，m)

2) trifluoromethanesulfonic acid (3R, 4R, 5S, 6R)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-1-alkenyl esters synthetic

In nitrogen gas stream, to (113 μ L 0.806mmol) behind the hexane solution (322 μ L, 0.787mmo l) of middle dropping n-Butyl Lithium, add THF (0.8mL) with ice bath refrigerative diisopropylamine.The solution that obtains is cooled to-78 ℃, drip (2R, 3S, 4R, 5R)-2,3, (205.9mg, THF 0.384mmol) (1mL) solution stirred 12 minutes under uniform temp 4-three benzyloxies-5-(benzyloxymethyl) pimelinketone.(452mg, THF 1.15mmol) (1.2mL) solution stirs reaction mixture 2.5 hours under uniform temp to drip N-(5-chloro-2-pyridyl) triflimide.Add saturated sodium bicarbonate aqueous solution and water, stopped reaction is used extracted with diethyl ether.With organic layer saturated common salt water washing, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10 → 1: 8)) make with extra care, obtain title compound (161.4mg, 63%).

¹H-NMR(CDCl ₃)δ：2.60-2.70(1H，m)、3.40-3.58(2H，m)、3.70(1H，dd，J＝9.9，9.7Hz)、3.90(1H，dd，J＝9.7，7.1Hz)、4.32-4.54(4H，m)、4.70-4.94(5H，m)、5.76-5.83(1H，m)、7.10-7.40(20H，m)

3) 1-(4-Ethylbenzyl)-3-[(3R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-1-thiazolinyl] benzene synthetic

In nitrogen gas stream, to trifluoromethanesulfonic acid (3R, 4R, 5S, 6R)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-1-alkenyl esters (656mg, 0.981mmol), K ₃PO ₄(250mg, 1.18mmol), KBr (140mg, 1.18mmol), 3-(4-Ethylbenzyl) phenyl-boron dihydroxide (283mg, 1.18mmol) and Pd (PPh ₃) ₄(56.6mg adds diox-water (10: 1) (12mL) in mixture 0.049mmol), with reaction mixture 100 ℃～105 ℃ following heated and stirred 26 hours.After being cooled to room temperature, add saturated aqueous common salt and water.Use extracted with diethyl ether,, use dried over sodium sulfate organic layer saturated common salt water washing.Underpressure distillation removes desolvates, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10 → 1: 8)) make with extra care, obtain title compound (510.0mg, 73%).

¹H-NMR(CDCl ₃)δ：1.19(3H，t，J＝7.6Hz)、2.58(2H，q，J＝7.6Hz)、2.64-2.75(1H，m)、3.54(1H，dd，J＝8.9，5.9Hz)、3.64(1H，dd，J＝8.9，3.5Hz)、3.68-3.79(1H，m)、3.92(2H，s)、4.07(1H，dd，J＝9.7，7.3Hz)、4.31(1H，d，J＝10.6Hz)、4.45(2H，s)、4.48(1H，d，J＝10.6Hz)、4.54(1H，d，J＝10.9Hz)、4.79-5.00(4H，m)、5.85-5.92(1H，m)、6.73-6.82(2H，m)、6.98-7.42(26H，m)

4) (1R, 2S, 3S, 6R)-4-[3-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-4-alkene-1,2,3-triol synthetic

In nitrogen gas stream, with 1-(4-Ethylbenzyl)-3-[(3R, 4R, 5S, 6S)-4,5,6-three benzyloxies-3-(benzyloxymethyl) hexamethylene-1-thiazolinyl] benzene (494.5mg, 0.692mmol) and penta-methyl benzene (1.05g, methylene dichloride 7.06mmol) (38mL) solution is cooled to-78 ℃, drips BCl ₃Dichloromethane solution (1.0M, 7.54mL).Reaction mixture was stirred 10 minutes under uniform temp, after stirring 1.5 hours under-70 ℃, add methyl alcohol (20mL).The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methyl alcohol: methylene dichloride (1: 20 → 1: 10)) carry out slightly refining, with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (46.2mg, 19%).

¹H-NMR(CD ₃OD)δ：1.19(3H，t，J＝7.6Hz)、2.27-2.44(1H，m)、2.58(2H，q，J＝7.6Hz)、3.44-3.68(3H，m)、3.76-3.94(3H，m)、4.45-4.57(1H，m)、5.74-5.84(1H，m)、6.95-7.25(8H，m)

MS(ESI ⁺)：372[M+H ₂O] ⁺

The HPLC hold-time: 18.37 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 65

(1R, 2R, 3S, 4R, 5R)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

1) (1R, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin and (1S, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin synthetic

In nitrogen gas stream, with 4-bromo-2-(4-Ethylbenzyl)-1-anisole (908mg, THF 2.98mmol) (10mL) solution is cooled to-78 ℃, and meanwhile drip n-Butyl Lithium hexane solution (2.70M, 1.03mL).Reaction mixture was stirred 10 minutes under uniform temp.In this solution, drip (2R, 3S, 4R, 5R)-2,3, (1.00g, THF 1.86mmol) (2mL) solution stirred 30 minutes down at-78 ℃ 4-three benzyloxies-5-(benzyloxymethyl) pimelinketone.Add saturated aqueous ammonium chloride and water, stopped reaction.Use ethyl acetate extraction, after organic layer is washed with water, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 5 → 1: 1)) make with extra care, obtain (1R, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin (0.32g, 23%) and (1S, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin (0.89g, 64%).

(1R)-isomer: ¹H-NMR (CDCl ₃) δ: 1.17 (3H, t, J=7.6Hz), 1.80-2.00 (2H, m), 2.20-2.36 (1H, m), 2.55 (2H, d, J=7.6Hz), 2.91 (1H, d, J=2.0Hz), 3.35-3.42 (1H, m), 3.65-4.05 (10H, m), 4.41-4.45 (3H, m), 4.59 (1H, d, J=10.7Hz), 4.81 (1H, d, J=10.7Hz), 4.87 (1H, d, J=10.7Hz), 4.90 (1H, d, J=10.7Hz), 6.78-6.84 (3H, m), 6.99-7.20 (6H, m), 7.20-7.40 (18H, m)

(1S)-isomer: ¹H-NMR (CDCl ₃) δ: 1.12 (3H, t, J=7.6Hz), 1.40-1.54 (2H, m)

1.78-1.88(1H，m)，2.35(1H，dd，J＝3.3，13.7Hz)，2.43(1H，s)，2.47(2H，q，J＝7.6Hz)、3.34(1H，dd，J＝0.9，8.9Hz)，3.53-3.72(4H，m)、3.80(3H，s)，3.86-3.93(2H，m)，4.41(2H，s)、4.49(1H，d，J＝10.7Hz)、4.67-4.79(2H，m)，4.83(1H，d，J＝10.7Hz)、5.02(1H，d，J＝11.7Hz)、6.78(1H，d，J＝8.4Hz)，7.00(2H，d，J＝7.9Hz)、7.10(2H，d，J＝7.9Hz)、7.14-7.20(2H，m)，7.21-7.40(18H，m)，7.56-7.63(2H，m)

2) (1R, 2R, 3S, 4R, 5R)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-5-(methylol) hexamethylene-1,2,3,4-tetrol synthetic

To (1R, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl)-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin (50.0mg, 0.067mmol) THF (0.5mL)-methyl alcohol (2mL) solution in add 20% palladium hydroxide catalyzer (10mg), in nitrogen atmosphere, at room temperature stirred 15 hours.After the catalyzer filtration, filtrate decompression is concentrated.With the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (20mg, 74%).

¹H-NMR(CD ₃OD)δ：1.22(3H，t，J＝7.6Hz)、1.65-1.84(2H，m)、2.01-2.14(1H，m)、2.60(2H，q，J＝7.6Hz)、3.39-3.46(1H，m)、3.62-3.75(4H，m)、3.82(3H，s)、3.94(2H，s)、6.94(1H，d，J＝8.4Hz)、7.06(2H，d，J＝8.2Hz)、7.13(2H，d，J＝8.2Hz)、7.30-7.38(2H，m)

MS(ESI ⁺)：420[M+H ₂O] ⁺

The HPLC hold-time: 17.70 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 66

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

1) 2-(4-Ethylbenzyl)-1-methoxyl group-4-[(1S, 2S, 3R, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl] benzene synthetic

With (the 1S that obtains among the embodiment 65,2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl] hexalin (124mg, 0.16mmol) methylene dichloride (2mL) solution be cooled to-5 ℃, add triethyl silicane (0.39mL, 2.44mmol).(0.12mL 1.6mmol), after stirring 1 hour under-5 ℃, adds saturated sodium bicarbonate aqueous solution with reaction mixture to add trifluoroacetic acid.Use dichloromethane extraction, after the water washing of organic layer usefulness saturated common salt, use dried over sodium sulfate.Underpressure distillation removes desolvates, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 9)) make with extra care, obtain title compound (10mg, 8%).

¹H-NMR(CDCl ₃)δ：1.17(3H，t，J＝7.6Hz)、1.58-1.96(3H，m)、2.56(2H，q，J＝7.6Hz)、2.55-2.70(1H，m)，3.43-3.62(5H，m)、3.78-4.00(6H，m)，4.43(2H，s)、4.44(1H，d，J＝9.9Hz)、4.56(1H，d，J＝10.8Hz)、4.82-4.93(3H，m)、6.75-6.82(3H，m)、6.99-7.18(9H，m)、7.20-7.38(15H，m)

2) (1R, 2R, 3S, 4S, 6R)-4-[3-(4-Ethylbenzyl)-4-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2,3-triol synthetic

To 2-(4-Ethylbenzyl)-1-methoxyl group-4-((1S, 2S, 3R, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl) benzene (10mg, 0.013mmol) THF (0.2mL)-methyl alcohol (1mL) solution in add 20% palladium hydroxide catalyzer (10mg), in nitrogen atmosphere, at room temperature stirred 13 hours.After the catalyzer filtration, filtrate decompression is concentrated.With the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (3.9mg, 75%).

¹H-NMR(CD ₃OD)δ：1.23(3H，t，J＝7.4Hz)、1.34-1.48(1H，m)、1.60-1.76(1H，m)、1.83(1H，dt，J＝13.5，3.5Hz)，2.48-2.66(3H，m)、3.30-3.38(2H，m)，3.42-3.52(1H，m)、3.58-3.65(1H，m)、3.77(1H，d，J＝4.0Hz)、3.82(3H，s)、3.92(2H，s)、6.91(1H，d，J＝8.2Hz)、7.02-7.14(6H，m)

MS(ESI ⁺)：406[M+H ₂O] ⁺

The HPLC hold-time: 12.53 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 67

(1R, 2R, 3S, 4R, 5R)-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

1) (3-bromo-4-ethoxyl phenenyl)-(4-ethylphenyl) methyl alcohol is synthetic

To magnesium (353mg adds THF (10mL) in 14.5mmol), drip again 1-bromo-4-ethylbenzene (2mL, 14.5mmol), reflux 1 hour.Reaction solution is cooled to 0 ℃, and (2.21g, THF solution (5mL) 9.68mmol) stirred 1.5 hours under uniform temp to add 3-bromo-4-ethoxy-benzaldehyde.Add saturated aqueous ammonium chloride, use ethyl acetate extraction.Use the saturated common salt water washing, use dried over mgso.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=normal hexane → normal hexane: ethyl acetate (3: 1)) make with extra care, obtain title compound (2.83g, 88%).

¹H-NMR(CDCl ₃)δ：1.22(3H，t，J＝7.6Hz)、1.45(3H，t，J＝7.0Hz)、?2.14(1H，d，J＝3.5Hz)、2.63(2H，q，J＝7.5Hz)、4.07(2H，q，J＝7.0Hz)、5.74(1H，d，J＝3.5Hz)、6.83(1H，d，J＝8.4Hz)、7.17(2H，d，J＝8.1Hz)、7.20-7.30(3H，m)、7.56(1H，d，J＝2.1Hz)

2) 2-bromo-1-oxyethyl group-4-(4-Ethylbenzyl) benzene is synthetic

Under 0 ℃, to (3-bromo-4-ethoxyl phenenyl)-(4-ethylphenyl) methyl alcohol (2.83g, add in dichloromethane solution 8.44mmol) (20mL) triethyl silicane (2.7mL, 16.9mmol) and boron trifluoride-ether coordination compound (1.2mL, 9.47mmol), stirred 3 hours.After adding methyl alcohol (50%)-water (4mL), use dichloromethane extraction.After the saturated common salt water washing, use dried over mgso.The solvent underpressure distillation is removed, the residue that obtains is made with extra care with silica gel column chromatography (developping solution=normal hexane → normal hexane-ethyl acetate (4% (v/v))), obtain title compound (2.69g, 100%).

¹H-NMR(CDCl ₃)δ：1.22(3H，t，J＝7.6Hz)、1.45(3H，t，J＝7.0Hz)、2.62(2H，q，J＝7.6Hz)、3.85(2H，s)、4.06(2H，q，J＝7.0Hz)、6.79(1H，d，J＝8.4Hz)、7.00-7.15(3H，m)、7.36(1H，d，J＝2.1Hz)

3) (1R, 2R, 3S, 4R, 5R)-and (1S, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl] hexalin synthetic

In nitrogen gas stream, with 2-bromo-1-oxyethyl group-4-(4-Ethylbenzyl) benzene (1.18g, THF 3.70mmol) (9mL) solution is cooled to-78 ℃, and meanwhile drip n-Butyl Lithium hexane solution (1.59M, 2.30mL, 3.66mmol).With reaction mixture after stirring between 1 hour under the uniform temp, drip (2R, 3S, 4R, 5R)-2,3, (1.50g, THF 2.80mmol) (4.5mL) solution stirred 10 minutes down at-78 ℃ 4-three benzyloxies-5-(benzyloxymethyl) pimelinketone.Add saturated aqueous ammonium chloride, stopped reaction.Use ethyl acetate extraction, after the water washing of organic layer usefulness saturated common salt, use dried over mgso.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain (1R) isomer (884mg, 41%) and (1S) isomer (740mg, 34%).

(1R) isomer: ¹H-NMR (CDCl ₃) δ: 1.23 (3H, t, J=7.6Hz), 1.37 (3H, t, J=7.0Hz), 1.70 (1H, dd, J=14.3,4.1Hz), 2.20-2.35 (1H, m), 2.62 (2H, q, J=7.6Hz), 2.67-2.82 (1H, m), 3.0-3.3 (1H, br), 3.43 (1H, dd, J=8.8,2.0Hz), 3.71 (1H, dd, J=9.8,9.8Hz), 3.83 (1H, dd, J=8.9,4.0Hz), 3.86-4.10 (3H, m), 3.91 (2H, s), 4.44 (2H, s), 4.48 (1H, d, J=10.3Hz), 4.58 (1H, br), 4.63 (1H, d, J=10.3Hz), 4.85 (1H, d, J=11.0Hz), 4.88 (1H, d, J=11.0Hz), 4.95 (1H, d, J=10.8Hz), 6.75 (1H, d, J=8.4Hz), 6.79 (2H, d, J=7.0Hz), 7.00-7.40 (24H, m), 7.53 (1H, d, J=2.0Hz)

(1S) isomer: ¹H-NMR (CDCl ₃) δ: 1.12 (3H, t, J=7.6Hz), 1.30 (3H, t, J=7.2Hz), 1.40-1.55 (1H, m), 1.76 (1H, dd, J=13.3,13.3Hz), 2.50 (2H, q, J=7.6Hz), 2.74 (1H, dd, J=13.7,3.2Hz), 3.38 (1H, dd, J=9.0,2.8Hz), 3.54 (1H, dd, J=9.0,5.3Hz), 3.64 (1H, dd, J=10.8,8.7Hz), 3.86 (1H, dd, J=9.5,9.5Hz), 3.89 (2H, s), 4.0-4.1 (2H, m), 4.39 (2H, s), 4.53 (1H, dd, J=11.0Hz), 4.64-4.72 (3H, m), 4.77 (1H, d, J=11.7Hz), 4.79 (1H, d, J=10.5Hz), 4.87 (1H, d, J=10.8Hz), 4.98 (1H, d, J=11.7Hz), 6.98-7.42 (25H, m), 7.67 (1H, d, J=1.8Hz)

4) (1R, 2R, 3S, 4R, 5R)-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-5-(methylol) hexamethylene-1,2,3,4-tetrol synthetic

To (1R, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl)-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl] hexalin (600mg, 0.772mmol) THF (6mL)-methyl alcohol (3mL) solution in add 20% palladium hydroxide catalyzer (60mg), in nitrogen atmosphere, stirred 2.5 hours.After the catalyzer filtration, filtrate decompression is concentrated.The residue that obtains is made with extra care with silica gel column chromatography (developping solution=methylene dichloride → dichloromethane methanol (12% (v/v))), obtained title compound (197mg, 61%).

¹H-NMR(CD ₃OD)δ：1.18(3H，t，J＝7.6Hz)、1.43(3H，t，J＝7.0Hz)、1.60(1H，dd，J＝14.3，4.1Hz)、2.01(1H，m)、2.43(1H，dd，J＝14.0，13.0Hz)、2.57(2H，q，J＝7.5Hz)、3.39(1H，dd，J＝10.5，9.3Hz)、3.60-3.68(3H，m)、3.85(2H，s)、4.03(2H，m)、4.34(1H，d，J＝9.2Hz)、6.82(1H，d，J＝8.2Hz)、6.99(1H，dd，J＝8.4Hz、2.3Hz)、7.45(1H，d，J＝2.3Hz)

MS(ESI ⁺)：434[M+H ₂O] ⁺

The HPLC hold-time: 18.71 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 68

(1R, 2R, 3S, 4S, 6R)-4-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

1) (1R, 2R, 3S, 4S, 6R)-4-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-1,2,3-triol synthetic

(the 1S that in embodiment 67, obtains, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[2-oxyethyl group-5-(4-Ethylbenzyl) phenyl] hexalin (402mg, 0.517mmol) THF (4mL)-methyl alcohol (2mL) solution in add 20% palladium hydroxide catalyzer (78mg), in nitrogen atmosphere, stirred 19 hours.After the catalyzer filtration, filtrate decompression is concentrated.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol=10: 1) make with extra care, obtain title compound (42mg, 20%).

¹H-NMR(CD ₃OD)δ：1.18(3H，t，J＝7.6Hz)、1.25-1.50(1H，m)、1.38(3H，t，J＝7.0Hz)、1.62(1H，m)、1.78(1H，m)、2.57(2H，q，J＝7.6Hz)、2.95-3.15(1H，br)、3.25-3.33(2H，m)、3.54(1H，dd，J＝10.8，6.1Hz)、3.73(1H，dd，J＝10.8、3.8Hz)、3.65-3.85(1H，m)、3.83(2H，s)、4.00(2H，q，J＝7.0Hz)、6.81(1H，d，J＝8.4Hz)、6.94(1H，dd，J＝8.3、2.1Hz)、7.04(1H，d，J＝1.7Hz)、7.06(4H，s)

MS(ESI ⁺)：401[M] ⁺

The HPLC hold-time: 12.98 minutes

Embodiment 69-74

Use corresponding starting raw material and reagent, similarly operate with embodiment 67 or embodiment 68 respectively, obtain the purpose compound.

Embodiment 69

(1R, 2R, 3S, 4R, 5R)-and 1-[5-(4-Ethylbenzyl)-2, the 4-Dimethoxyphenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

¹H-NMR(CD ₃OD)δ：1.17(3H，t，J＝7.6Hz)、1.61(1H，dd，J＝13.9，3.8Hz)、1.90-2.10(1H，m)、2.22(1H，dd，J＝13.9，13.2Hz)、2.55(2H，q，J＝7.6Hz)、3.32-3.42(1H，m)、3.58-3.70(3H，m)、3.76-3.88(2H，m)、3.80(3H，s)、3.84(3H，s)、4.19(1H，d，J＝9.1Hz)、6.58(1H，s)、7.00(2H，d，J＝8.2Hz)、7.06(2H，d，J＝8.2Hz)、7.35(1H，s)

MS(ESI ⁺)：455[M+Na] ⁺

The HPLC hold-time: 17.83 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 70

(1R, 2R, 3S, 4S, 6R)-and 4-[5-(4-Ethylbenzyl)-2, the 4-Dimethoxyphenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.17(3H，t，J＝7.6Hz)、1.24-1.48(1H，m)、1.52-1.82(2H，m)、2.56(2H，d，J＝7.6Hz)、2.86-3.08(1H，m)、3.24-3.29(1H，m)、3.48-3.67(2H，m)、3.68-3.84(3H，m)、3.79(3H，s)、3.81(3H，s)、6.56(1H，s)、6.93(1H，s)、7.01(2H，d，J＝8.6Hz)、7.05(2H，d，J＝8.6Hz)

MS(ESI ⁺)：416[M] ⁺

The HPLC hold-time: 18.26 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 71

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-aminomethyl phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

¹H-NMR(CD ₃OD)δ：1.19(3H，t，J＝7.6Hz)、1.70(1H，m)、1.94(1H，m)、2.05(1H，m)、2.53(3H，s)、2.58(2H，q，J＝7.6Hz)、3.40(1H，d，J＝9.2Hz)、3.67(2H，d，J＝4.6Hz)、3.73(1H，d，J＝9.2Hz)、3.87(2H，s)、4.01(1H，d，J＝9.2Hz)、6.91(1H，dd，J＝7.6，1.5Hz)、7.01(1H，d，J＝7.6Hz)、7.07(4H，m)、7.42(1H，s)

MS(ESI ⁺)：409[M+Na] ⁺

Embodiment 72

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-aminomethyl phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.19(3H，t，J＝7.6Hz)、1.24-1.37(1H，m)、1.59-1.81(2H，m)、2.30(3H，s)、2.57(2H，q，J＝7.6Hz)、2.93(1H，m)、3.34(2H，m)、3.50-3.63(2H，m)、3.75(1H，dd，J＝10.7，4.2Hz)、3.86(2H，s)、6.87(1H，d，J＝7.6Hz)、7.03(1H，d，J＝7.6Hz、2.1Hz)、7.07(4H，s)、7.11(1H，s)

MS(ESI ^-)：369[M-H] ^-

Embodiment 73

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

¹H-NMR(CD ₃OD)δ：1.13(3H，t，J＝7.6Hz)、1.56(1H，dd，J＝14.1，3.9Hz)、1.94-2.04(1H，m)、2.24(1H，dd，J＝13.9，13.2Hz)、2.51(2H，q，J＝7.5Hz)、3.24-3.37(1H，m)、3.57-3.63(3H，m)、3.74(3H，s)、3.80-3.90(2H，m)、4.22(1H，d，J＝9.1Hz)、6.80(1H，d，J＝8.4Hz)、6.95-7.01(5H，m)、7.41(1H，d，J＝1.2Hz)

MS(ESI ⁺)：425[M+Na] ⁺

The HPLC hold-time: 11.69 minutes

Embodiment 74

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.18(3H，t，J＝7.6Hz)、1.24-1.50(1H，m)、1.54-1.85(2H，m)、2.57(2H，d，J＝7.6Hz)、2.90-3.18(1H，m)、3.24-3.34(2H，m)、3.54(1H，dd，J＝10.7，5.9Hz)、3.60-3.78(2H，m)、3.76(3H，s)、3.83(2H，s)、6.82(1H，d，J＝8.4Hz)、6.96(1H，dd，J＝8.4，2.0Hz)、7.01-7.11(5H，m)

MS(ESI ⁺)：404[M+H ₂O] ⁺

The HPLC hold-time: 12.33 minutes

Embodiment 75

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-Trifluoromethoxyphen-l]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

Use corresponding starting raw material and reagent, similarly operate, obtain the purpose compound with embodiment 67.

¹H-NMR(CD ₃OD)δ：1.17(3H，t，J＝7.6Hz)、1.73(1H，d，J＝10.1Hz)、2.00-2.12(2H，m)、2.58(2H，q，J＝7.5Hz)、3.35(1H，dd，J＝9.3，9.3Hz)、3.58-3.72(2H，m)、3.66(1H，dd，J＝9.2，9.2Hz)、3.93(2H，s)、3.99(1H，d，J＝8.9Hz)、7.09(4H，s)、7.13(2H，m)、7.69(1H，d，J＝1.4Hz)

MS(ESI ⁺)：474[M+Na] ⁺

The HPLC hold-time: 13.09 minutes

Embodiment 76-78

Use corresponding starting raw material and reagent, similarly operate with embodiment 68 respectively, obtain the purpose compound.

Embodiment 76

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-isopropyl benzyl)-2-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.21(6H，d，J＝6.9Hz)、1.29-1.42(1H，m)、1.59-1.81(2H，m)、2.78-2.89(1H，m)、3.06-3.10(1H，m)、3.26-3.34(2H，m)、3.55(1H，dd，J＝10.7，6.0Hz)、3.62-3.85(5H，m)、3.84(2H，s)、6.82(1H，d，J＝8.5Hz)、6.96(1H，dd，J＝8.2，2.2Hz)、7.05-7.11(5H，m)

MS(ESI ⁺)：400[M] ⁺

The HPLC hold-time: 13.07 minutes

Embodiment 77

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-Ethylbenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.24(3H，t，J＝7.5Hz)、1.43-1.53(1H，m)、1.61-1.78(1H，m)、1.85(1H，dt，J＝13.4，3.7Hz)，2.56-2.68(3H，m)、3.29-3.40(2H，m)、3.50-3.66(2H，m)、3.80(1H，dd，J＝10.9，3.9Hz)、3.94(2H，s)、7.04-7.27(8H，m)

MS(ESI ⁺)：357[M] ⁺

The HPLC hold-time: 12.12 minutes

Embodiment 78

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-hydroxybenzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

¹H-NMR(CD ₃OD)δ：1.43-1.52(1H，m)、1.64-1.78(1H，m)、1.85(1H，dt，J＝12.5，3.7Hz)、2.55-2.66(1H，m)、3.33-3.40(2H，m)、3.50-3.64(2H，m)、3.76-3.84(1H，m)、3.88(2H，s)、6.68-6.74(2H，m)、7.00-7.14(5H，m)、7.20-7.25(1H，m)

MS(ESI ⁺)：362[M+H ₂O] ⁺

The HPLC hold-time: 13.70 minutes

Embodiment 79

(1R, 2R, 3S, 4S, 6R)-4-[5-(4-Ethylbenzyl)-2-hydroxy phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

In nitrogen gas stream, with (1R, 2R, the 3S that obtains among the embodiment 74,4S, 6R)-4-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl]-6-(methylol) hexamethylene-1,2, (40mg, methylene dichloride 0.1mmol) (1mL) solution is cooled to-78 ℃ to the 3-triol, drips BBr ₃Dichloromethane solution (1.0M, 0.31mL).Under uniform temp, stirred 10 minutes, drip BBr in ice-cold stirring down again after 2 hours again ₃Dichloromethane solution (0.2mL).Under uniform temp, stir after 3.5 hours, add sodium hydrate methanol solution (0.93mL).The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (3.5mg, 9.1%).

¹H-NMR(CD ₃OD)δ：0.87-0.98(1H，s)、1.19(3H，t，J＝7.8Hz)、1.39-1.52(1H，m)、1.59-1.66(1H，m)、1.78-1.83(1H，dt，J＝13.5，3.6Hz)、2.56(2H，q，J＝7.8，7.5Hz)、2.96-3.07(1H，m)、3.34(1H，s)、3.54-3.59(1H，m)、3.62-3.69(1H，m)、3.72(1H，dd，J＝6.6，3.9Hz)、3.80(2H，s)、6.68(1H，d，J＝8.4Hz)、6.80(1H，dd，J＝8.4，2.0Hz)、6.99(1H，s)、7.05(4H，s)

MS(ESI ⁺)：372[M] ⁺

The HPLC hold-time: 11.2 minutes

Embodiment 80

(1R, 2R, 3S, 4S, 6R)-4-[3-(4-cyclopropyl benzyl) phenyl]-6-(methylol) hexamethylene-1,2, the 3-triol

1) 4-[3-((3aS, 4S, 5aR, 9aR, 9bR)-2,2,8,8-tetramethyl--six hydrogen [1,3] dioxa cyclopentenyl [dioxolo] [4 ', 5 ': 3,4] benzo [1,2-d] [1,3] dioxines [dioxin]-4-yl) benzyl] phenol synthetic

Under 0 ℃, (1R, 2R, the 3S that in embodiment 78, obtain, 4S, 6R)-4-[3-(4-hydroxybenzyl) phenyl]-6-(methylol) hexamethylene-1,2,3-triol (47mg, 0.136mmol) N, add 2 in dinethylformamide (1mL) solution, 2-Propanal dimethyl acetal (142mg, 1.36mmol) then adds tosic acid hydrate (2mg).Reaction solution was at room temperature stirred 30 minutes, add saturated aqueous ammonium chloride, stopped reaction.With the mixture ethyl acetate extraction, after organic layer washed with water, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (34mg, 59%).

¹H-NMR(CDCl ₃)δ：1.11-1.24(1H，m)、1.42(6H，s)，1.46(3H，s)，1.53(3H，s)，1.73(1H，dt，J＝13.7，3.9Hz)、1.80-1.93(1H，m)，2.94(1H，dt，J＝4.0，11.0Hz)、3.59-3.92(7H，m)、4.85(1H，s)、6.71-6.76(2H，m)、7.00-7.08(5H，m)、7.19-7.23(1H，m)

2) trifluoromethanesulfonic acid 4-[3-((3aS, 4S, 5aR, 9aR, 9bR)-2,2,8,8-tetramethyl--six hydrogen-[1,3] dioxa cyclopentenyl [4 ', 5 ': 3,4] benzo [1,2-d] [1,3] dioxine-4-yl) benzyl] phenylester synthetic

With 4-[3-((3aS, 4S, 5aR, 9aR, 9bR)-2,2,8,8-tetramethyl--six hydrogen-[1,3] dioxa cyclopentenyl [4 ', 5 ': 3,4] benzyl benzo [1,2-d] [1,3] dioxine-4-yl)] phenol (34mg, 0.08mmol) be dissolved in the methylene dichloride (0.8mL), stir down ice-cold.Add pyridine (15mg, 0.19mmol), 2-[N, N-two (trifluoromethane sulfonyl group) amino] pyridine (34mg, 0.096mmol), then add N, N-dimethyl aminopyridine (1mg) at room temperature stirred 30 minutes.In reaction solution, add water, stopped reaction.With the mixture dichloromethane extraction, after organic layer washed with water, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (37mg, 83%).

¹H-NMR(CDCl ₃)δ：1.11-1.24(1H，m)、1.42(6H，s)，1.43(3H，s)，1.53(3H，s)，1.74(1H，dt，J＝13.7，3.9Hz)、1.80-1.93(1H，m)，2.96(1H，dt，J＝11.1，3.6Hz)、3.59-3.92(5H，m)、3.98(2H，s)、7.00-7.03(2H，m)、7.10-7.35(6H，m)

3) (3aS, 4S, 5aR, 9aR, 9bR)-and 4-[3-(4-cyclopropyl benzyl) phenyl]-2,2,8,8-tetramethyl--six hydrogen [1,3] dioxa cyclopentenyl [4 ', 5 ': 3,4] benzo [1,2-d] [1,3] dioxine synthetic

In nitrogen atmosphere, to trifluoromethanesulfonic acid 4-[3-((3aS, 4S, 5aR, 9aR, 9bR)-2,2,8,8-tetramethyl--six hydrogen [1,3] dioxa cyclopentenyl [4 ', 5 ': 3,4] benzyl benzo [1,2-d] [1,3] dioxine-4-yl)] and phenylester (38mg, 0.068mmol), K ₃PO ₄(65mg, 0.31mmol), Sodium Bromide (7mg, 0.068mmol), cyclopropylboronic acid (9mg, 0.10mmol) and Pd (PPh ₃) ₄(8.0mg adds toluene (0.5mL)-water (0.017mL) in mixture 0.007mmol), under 100 ℃, with reaction mixture heated and stirred 6 hours.After being cooled to room temperature, add water.Use ethyl acetate extraction,, use dried over sodium sulfate organic layer saturated common salt water washing.Underpressure distillation removes desolvates, with the residue that obtains with preparing TLC (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain title compound (10mg, 33%).

¹H-NMR(CDCl ₃)δ：0.62-0.68(2H，m)，0.89-0.96(2H，m)，1.10-1.24(1H，m)、1.42(3H，s)，1.43(3H，s)，1.46(3H，s)，1.54(3H，s)，1.74(1H，dt，J＝13.7，3.9Hz)、1.80-1.93(2H，m)，2.94(1H，dt，J＝10.9，3.6Hz)、3.59-3.96(8H，m)、6.96-7.07(7H，m)、7.16-7.25(1H，m)

4) (1R, 2R, 3S, 4S, 6R)-4-[3-(4-cyclopropyl benzyl) phenyl]-6-(methylol) hexamethylene-1,2,3-triol synthetic

With (3aS, 4S, 5aR, 9aR, 9bR)-4-[3-(4-cyclopropyl benzyl) phenyl]-2,2,8,8-tetramethyl--six hydrogen [1,3] dioxa cyclopentenyl [4 ', 5 ': 3,4] benzo [1,2-d] [1,3] dioxine (10mg, 0.022mmol) De diox (0.2mL) solution is cooled to 0 ℃, drips 2N aqueous hydrochloric acid (0.2mL).Reaction mixture after stirring 3 hours under the uniform temp, is added saturated sodium bicarbonate aqueous solution.Use dichloromethane extraction,, use dried over sodium sulfate organic layer saturated common salt water washing.The solvent underpressure distillation is removed, with the residue that obtains with preparation TLC (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (4.5mg, 51%).

¹H-NMR(CD ₃OD)δ：0.63-0.68(2H，m)、0.91-0.98(2H，m)、1.42-1.52(1H，m)、1.62-1.78(1H，m)、1.80-1.94(2H，m)、2.54-2.66(1H，m)、3.33-3.40(2H，m)、3.50-3.68(2H，m)、3.79(1H，dd，J＝10.9，3.9Hz)、3.93(2H，s)、6.85-7.16(7H，m)、7.21-7.26(1H，m)

MS(ESI ⁺)：386[M+H ₂O] ⁺

The HPLC hold-time: 18.49 minutes

＜HPLC condition determination 〉

Pillar: YMC-Pack ODS-A 6.0 * 150mm, 5 μ m

Flow velocity: 1.5mL/ branch

Column temperature: room temperature

Testing conditions: to the full wave total amount mapping of 230～400nm

Embodiment 81

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-fluorophenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

1) (1R, 2R, 3S, 4R, 5R)-and (1S, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[5-(4-Ethylbenzyl)-2-fluorophenyl] hexalin synthetic

In nitrogen gas stream, under-78 ℃, (2.44M 0.368mL), stirred 2 hours under uniform temp the hexane solution of dropping n-Butyl Lithium in the diethyl ether solution (3.0mL) of 2-bromo-4-(4-Ethylbenzyl)-1-fluorobenzene (0.263g, 0.900mmol).Add 2,3,4, the THF solution (1.5mL) of-three benzyloxies-5-methylcyclohexanone (0.483g, 0.900mmol) stirred 2 hours.Add saturated aqueous ammonium chloride, make reaction terminating, use extracted with diethyl ether.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 4)) make with extra care, obtain (1R) isomer (0.117g, 17.3%) of title compound and (1S) isomer (0.311g, 46.1%).

(1R) isomer: ¹H-NMR (CDCl ₃) δ: 1.15-1.32 (and 3H, m), 1.81-1.92 (1H, br), 2.20-2.38 (2H, br), 2.62 (2H, q, J=9.8Hz), 3.07 (1H, br), 3.40-3.55 (1H, m), 3.66-3.80 (2H, m), 3.84-4.06 (4H, m), 4.28 (1H, d, J=12.3Hz), 4.45 (2H, s), 4.58 (2H, t, J=12.1Hz), 4.80-4.96 (3H, m), 6.76-6.84 (2H, m), 6.86-7.00 (1H, m), 7.02-7.44 (23H, m), 7.52-7.60 (1H, m)

(1S) isomer: ¹H-NMR (CDCl ₃) δ: 1.13 (3H, t, J=1.5Hz), 1.34-1.55 (1H, br), 1.84 (1H, t, J=2.4Hz) 2.50 (2H, q, J=1.5Hz) 2.75 (1H, dd, J=2.4,0.9Hz), 2.93 (1H, d, J=0.9Hz), 3.37 (1H, dd, J=10.5,6.6Hz), 3.57-3.78 (3H, m), 3.86-4.06 (3H, m), 4.40-5.00 (8H, m), 6.80-7.60 (26H, m), 7.72-7.84 (1H, m)

2) (1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-fluorophenyl]-5-(methylol) hexamethylene-1,2,3,4-tetrol synthetic

To (1R, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[5-(4-Ethylbenzyl)-2-fluorophenyl] add 20% palladium hydroxide catalyzer (40mg) in methyl alcohol-THF (1: 1) mixing solutions (20mL) of hexalin (271mg, 0.361mmol).In nitrogen atmosphere, stir after 30 minutes, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (44.6mg, 31.6%).

¹H-NMR(CD ₃OD)δ：1.18(3H，t，J＝7.2Hz)、1.15-1.26(1H，m)、1.48(1H，dd，J＝13.5，13.2Hz)、2.57(2H，q，J＝7.8Hz)、2.73(1H，dd，J＝13.5，3.0Hz)、3.30-3.80(1H，m)、3.50(1H，dd，J＝9.9，5.7Hz)、3.53-3.66(2H，m)、3.83-3.92(3H，m)、6.94(1H，dd，J＝12.3，8.1Hz)、7.00-7.25(5H，m)、7.95(1H，dd，J＝7.8，1.8Hz)

MS(ESI ⁺)：413[M+Na] ⁺

The HPLC hold-time: 10.9 minutes

Embodiment 82

(1S, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-fluorophenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol

(the 1S that in embodiment 81, obtains, 2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[5-(4-Ethylbenzyl)-2-fluorophenyl] add 20% palladium hydroxide catalyzer (7.5mg) in methyl alcohol-THF (1: 1) mixing solutions (1.4mL) of hexalin (33mg, 0.044mmol).In nitrogen atmosphere, stir after 2.5 hours, catalyzer is filtered.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=methyl alcohol: methylene dichloride (1: 10)) make with extra care, obtain title compound (17.5mg, 100%).

¹H-NMR(CD ₃OD)δ：1.18(3H，t，J＝7.5Hz)、1.70-1.79(1H，m)、?1.98-2.11(2H，m)、2.57(2H，q，J＝7.8Hz)、3.32-3.45(1H，m)、3.60-3.71(3H，m)、3.90(2H，s)、3.94(1H，d，J＝9.0Hz)、6.91(1H，dd，J＝12.3，8.1Hz)、7.02-7.12(5H，m)、7.53(1H，dd，J＝7.8、2.4Hz)

MS(ESI ⁺)：413[M+Na] ⁺

The HPLC hold-time: 11.7 minutes

Embodiment 83

(1R, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol

Use corresponding starting raw material and reagent, similarly operate, obtain the purpose compound with embodiment 81.

¹H-NMR(CD ₃OD)δ：1.62-1.80(2H，m)、1.94-2.10(1H，m)、3.40(1H，dd，J＝10.5，8.7Hz)、3.62-3.72(4H，m)、3.73(3H，s)、3.89(2H，s)、6.70-6.82(2H，m)、7.00-7.03(2H，m)、7.06-7.12(2H，m)、7.22(1H，t，J＝7.8Hz)、7.27-7.32(1H，m)、7.34-7.37(1H，m)

MS(ESI ⁺)：375[M+H] ⁺

The HPLC hold-time: 9.53 minutes

Embodiment 84

(1S, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol

¹H-NMR(CD ₃OD)δ：1.28-1.44(1H，m)、1.56(1H，t，J＝13.2Hz)、2.35(1H，dt，J＝13.5，3.0Hz)、3.45(1H，dd，J＝11.1，6.0Hz)、3.60-3.70(3H，m)、3.73(3H，s)、3.89(2H，s)、6.77-6.82(2H，m)、7.00-7.05(1H，m)、7.06-7.13(2H，m)、7.20(1H，t，J＝7.8Hz)、7.60-7.65(1H，m)、7.68-7.70(1H，m)

MS(ESI ⁺)：397[M+Na] ⁺

The HPLC hold-time: 14.6 minutes

Embodiment 85

(1R, 2R, 3S, 4S, 6R)-4-[1-(4-Ethylbenzyl)-1H-indol-3-yl]-6-(methylol) hexamethylene-1,2, the 3-triol

1) 1-(4-Ethylbenzyl)-1H-indoles is synthetic

In ethanol (200mL) solution of indoles (4.0g, 34.1mmol), add potassium hydroxide (2.40g, 42.6mmol), at room temperature stirred 2 hours.The solvent underpressure distillation is removed.Residue is dissolved in the acetone (200mL), adds 1-chloromethyl-4-ethylbenzene (5.28g, 34.1mmol).After reaction solution at room temperature stirred diel, use diatomite filtration, the filtrate decompression distillation is removed.With the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 500)) make with extra care, obtain title compound (3.8g, 47%).

¹H-NMR(CDCl ₃)δ：1.19(3H，t，J＝7.6Hz)、2.60(2H，q，J＝7.6Hz)、5.27(2H，s)、6.53(1H，dd，J＝3.1，0.7Hz)、7.03(2H，d，J＝7.6Hz)、7.07-7.22(5H，m)、7.29(1H，d，J＝8.0Hz)、7.64(1H，d，J＝6.8Hz)

2) 3-bromo-1-(4-Ethylbenzyl)-1H-indoles is synthetic

At room temperature, in the DMF (20mL) of bromine (0.46mL, 8.93mmol) solution, drip DMF (20mL) solution of 1-(4-Ethylbenzyl)-1H-indoles (2.0g, 8.50mmol).The reaction solution stirring after 2 hours, is poured in the ice-cold metabisulfite solution.Use ethyl acetate extraction, with organic layer saturated sodium bicarbonate aqueous solution, saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.Carry out recrystallization with ethyl acetate and normal hexane, obtain title compound (1.68g, 63%).

¹H-NMR(CDCl ₃)δ：1.20(3H，t，J＝7.6Hz)、2.61(2H，q，J＝7.6Hz)、5.23(2H，s)、7.05(2H，dd，J＝8.0Hz)、7.11-7.22(5H，m)、7.30(1H，dd，J＝6.5，1.9Hz)、7.57(1H，dd，J＝6.5，1.9Hz)

3) (2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[1-(4-Ethylbenzyl)-1H-indol-3-yl] hexalin synthetic

In nitrogen gas stream, THF (8mL) solution of 3-bromo-1-(4-Ethylbenzyl)-1H-indoles (427mg, 1.36mmol) is cooled to-78 ℃, drip the hexane solution (1.6M, 0.89mL, 1.43mmol) of n-Butyl Lithium.Reaction mixture was stirred 5 minutes under uniform temp.In this solution, drip (2R, 3S, 4R, 5R)-2,3, THF (5.6mL) solution of 4-three benzyloxies-5-(benzyloxymethyl) pimelinketone (875mg, 1.63mmol) stirred 2 hours down at-78 ℃.Add saturated aqueous ammonium chloride, stopped reaction.Use ethyl acetate extraction, after organic layer is washed with water, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 10)) make with extra care, obtain low polar isomer (354mg, 34%) and high polar isomer (115mg, 11%) in the title compound.

Low polar isomer: ¹H-NMR (CDCl ₃) δ: 1.18 (3H, t, J=7.2Hz), 1.93 (2H, m), 2.40 (1H, m), 2.61 (2H, q, J=7.2Hz), 3.40-5.22 (15H, m), 7.02-7.40 (28H, m), 7.93 (1H, d, J=8.0Hz)

High polar isomer: ¹H-NMR (CDCl ₃) δ: 1.18 (3H, t, J=7.6Hz), 2.40 (1H, m), 2.38 (2H, m), 2.58 (2H, q, J=7.6Hz), 3.41-5.24 (15H, m), 6.83 (1H, d, J=8.0Hz), 7.03-7.34 (27H, m), 7.75 (1H, d, J=7.6Hz)

4) 1-(4-Ethylbenzyl)-3-[(1S, 2S, 3R, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl]-1H-indoles synthetic

In nitrogen gas stream, under 0 ℃, to (2R, 3S, 4R, 5R)-2,3,4-three benzyloxies-5-benzyloxymethyl-1-[1-(4-Ethylbenzyl)-1H-indol-3-yl] drip triethyl silicane (0.21mL, 1.22mmol) in methylene dichloride (6mL) solution of hexalin (469mg, 0.61mmol).(0.093mL 0.73mmol), stirs reaction mixture 2 hours down at 0 ℃ to spend 5 minutes dropping boron trifluoride diethyl etherate coordination compoundes.Add saturated sodium bicarbonate aqueous solution, use dichloromethane extraction.With organic layer saturated common salt water washing, use dried over sodium sulfate.The solvent underpressure distillation is removed, with the residue that obtains with silica gel column chromatography (developping solution=ethyl acetate: normal hexane (1: 15)) make with extra care, obtain title compound (232mg, 51%).

¹H-NMR(CDCl ₃)δ：1.17(3H，t，J＝7.6Hz)、1.87(2H，m)、2.27(1H，m)、2.58(2H，q，J＝7.6Hz)、3.36(1H，dd，J＝9.0，1.7Hz)、3.59-3.70(2H，m)、3.88-4.00(2H，m)、4.12(1H，t，J＝8.6Hz)、4.38(2H，s)、4.47(1H，d，J＝11.4Hz)、4.54(1H，d，J＝2.7Hz)、4.58(1H，d，J＝3.1Hz)、4.80(1H，d，J＝10.7Hz)、4.89(1H，d，J＝10.7Hz)、4.98(1H，d，J＝10.7Hz)、5.25(2H，d，J＝4.9Hz)、6.97(2H，d，J＝8.4Hz)、7.05(2H，d，J＝8.0Hz)、7.08-7.35(24H，m)、7.62(1H，d，J＝7.2Hz)

5) 4-[1-(4-Ethylbenzyl)-1H-indol-3-yl]-6-(methylol) hexamethylene-1,2,3-triol synthetic

In nitrogen gas stream, under ice-cold, to 1-(4-Ethylbenzyl)-3-[(1S, 2S, 3R, 4R, 5R)-2,3,4-three benzyloxies-5-(benzyloxymethyl) cyclohexyl]-add dimethyl thioether (0.72mL) and boron trifluoride diethyl etherate coordination compound (0.36mL, 2.8mmol) in the methylene dichloride (4.7mL) of 1H-indoles (213mg, 0.28mmol).After at room temperature stirring 64 hours, under ice-cold, add entry, use dichloromethane extraction.With organic layer saturated common salt water washing, after dry (anhydrous magnesium sulfate), underpressure distillation removes and desolvates.With the residue that obtains with silica gel column chromatography (developping solution=methylene dichloride: methyl alcohol (50: 1)) make with extra care, obtain title compound (45mg, 41%).

¹H-NMR(CD ₃OD)δ：1.17(3H，t，J＝7.6Hz)、1.66(1H，m)、1.79(1H，m)、2.16(1H，m)、2.58(2H，q，J＝7.6Hz)、3.33(1H，m)、3.57(1H，dd，J＝10.7，6.1Hz)、3.69(1H，dd，J＝10.7，4.2Hz)、3.76-3.88(3H，m)、5.29(2H，s)、6.98-7.11(6H，m)、7.24(1H，d，J＝8.0Hz)、7.30(1H，s)、7.62(1H，d，J＝7.6Hz)

MS(ESI ⁺)：396[M+H] ⁺

The structural formula of the compound of the foregoing description is shown in the table 1-table 10.

[table 1]

[table 2]

[table 3]

[table 4]

[table 5]

[table 6]

[table 7]

[table 8]

[table 9]

[table 10]

Test example 1

People Na ^± Glucose symporter (SGLT1 and SGLT2) activity inhibition validation test

1) people SGLT1 preparation of expression vectors

To make template from the cDNA storehouse (Clontech corporate system) of people's small intestine, use the synthetic DNA primer, and utilize KOD+DNA polysaccharase (society's system is spun by Japan) to carry out PCR, people SGLT1cDNA will be increased.Then, the fragment that has increased is cloned on the pcRII-Topo carrier with Topo TA Cloning Dual Promoter test kit (Invitrogen corporate system), import in the colibacillary active cells (Invitrogen corporate system, TOP10), the clone's product that demonstrates Ampicillin Trihydrate [ア Application ピシリ Application ampicillin] patience is bred in the LB substratum that contains Ampicillin Trihydrate (50mg/L).By the intestinal bacteria that bred according to the refining plasmid of ordinary method (with reference to Maniatis etc., Molecular Cloning).This plasmid is made template, use has imported the synthetic DNA primer of restriction enzyme recognition site, utilize the KOD+DNA polysaccharase to carry out PCR, with people SGLT1 cDNA (at the upstream adduction Eco RI recognition site and in the downstream addition fragment of Hind III recognition site) amplification.This amplified fragments is carried out Eco RI and Hind III digestion, use Rapid DNA Ligation test kit (Roche Diagnostics corporate system) digestion fragment to be attached at the same identification position of expression vector pcDNA3.1 (-) (Invitrogen corporate system).The expression vector that links up is imported in the colibacillary active cells (Invitrogen corporate system, DH5 α), it is bred in containing the LB substratum of Ampicillin Trihydrate, adopt ordinary method to obtain people SGLT1 expression vector.

2) people SGLT2 preparation of expression vectors

To make template from the cDNA storehouse (Clontech corporate system) of people's kidney, use the synthetic DNA primer, and utilize the KOD+DNA polysaccharase to carry out PCR, people SGLT2 cDNA will be increased.Then, the fragment that has increased is cloned on the pcRII-Topo carrier with Topo TA Cloning Dual Promoter test kit, import in the colibacillary active cells (TOP10), the clone's product that demonstrates Ampicillin Trihydrate patience is bred in the LB substratum that contains Ampicillin Trihydrate (50mg/L).By the intestinal bacteria that bred according to the refining plasmid of ordinary method.This plasmid is made template, use has imported the synthetic DNA primer of restriction enzyme recognition site, utilize the KOD+DNA polysaccharase to carry out PCR, with people SGLT2 cDNA (at the upstream adduction Xho I recognition site and at the downstream adduction fragment of Hind III recognition site) amplification.This amplified fragments is carried out Xho I and HindIII digestion, use Rapid DNA Ligation test kit digestion fragment to be attached at the same identification position of expression vector pcDNA3.1 (-).The expression vector that links up is imported in the colibacillary active cells (DH5 α), it is bred in containing the LB substratum of Ampicillin Trihydrate, adopt ordinary method to obtain people SGLT2 expression vector.

3) preparation of people SGLT1 stably express [stable expression] cell and people SGLT2 stably express cell

Use FuGENE (Roche Diagnostics corporate system) to import in the CHO-K1 cell with people SGLT1 expression vector or the people SGLT2 expression vector that restriction enzyme Pvu I has digested.Behind the quiding gene, with cell in the DMEM substratum (Gibco corporate system) that contains penicillin (50U/mL, SIGMA corporate system), Streptomycin sulphate (50mg/L, SIGMA corporate system), Geneticin (200mg/L, Na カライテス Network society system) and 20% N of young serum of tire, at 37 ℃ down and at 5%CO ₂Exist down and cultivate about 3 weeks, obtain clone's product of Geneticin patience.As index, selecting from these clone's products and obtain can stably express people SGLT1 or the cell of people SGLT2 with the activity of the sugar (methyl-α-D-glucopyranoside) of picked-up sodium interdependence.

4) picked-up methyl-α-D-glucopyranoside is suppressed active mensuration

People SGLT1 stably express Chinese hamster ovary celI or the people SGLT2 stably express Chinese hamster ovary celI density by 30000～40000 cells/well is seeded on the 96 hole flat boards, cultivated 4～6 days.Then, the substratum of these culture plates is removed, add 150 μ L pre-treatments in per 1 hole with the damping fluid pH of buffer 7.4 of ethyl sulfonic acid 10mM, three (methylol) aminomethane (contain choline chloride 60 140mM, Repone K 2mM, calcium chloride 1mM, magnesium chloride 1mM, 2-[4-(2-hydroxyethyl)-1-piperazinyl]), under 37 ℃, left standstill 20 minutes.Remove the pre-treatment damping fluid, per 1 hole adds 50 μ L pre-treatment damping fluids again, leaves standstill under 37 ℃ 20 minutes.In damping fluid (pH of buffer 7.4 that contains sodium-chlor 140mM, Repone K 2mM, calcium chloride 1mM, magnesium chloride 1mM, methyl-α-D-glucopyranoside 1mM, [4-(2-hydroxyethyl)-1-piperazinyl] ethyl sulfonic acid 10mM, three (methylol) aminomethane) 100mL, add methyl-α-D-(U-of 6.3mL ¹⁴C) glucopyranoside (Amersham Pharmacia Biotech corporate system, 200mCi/L) and mixing, make picked-up and use damping fluid, use by dissolving in solution that test compound forms in damping fluid in this picked-up as inhibition determination of activity damping fluid.In addition, in contrast, use the picked-up damping fluid that does not contain test compound.And then basic intake when not having test compound and sodium in order to measure has prepared the basis picked-up that replaces sodium-chlor and contain the 140mM choline chloride 60 after the same method with damping fluid and use it in the mensuration.From the hole of culture plate, remove the pre-treatment damping fluid, will suppress determination of activity and in per 1 hole, add 35 μ L, under 37 ℃, left standstill 45 minutes with damping fluid.To suppress determination of activity removes with damping fluid, add 300 μ L washing in per 1 hole with the damping fluid pH of buffer 7.4 of ethyl sulfonic acid 10mM, three (methylol) aminomethane (contain choline chloride 60 140mM, Repone K 2mM, calcium chloride 1mM, magnesium chloride 1mM, methyl-α-D-glucopyranoside 10mM, 2-[4-(2-hydroxyethyl)-1-piperazinyl]), and be removed very soon.This washing operation is carried out 1 time again, add 30mL cytolysate (sodium hydroxide 1M, Sodium Lauryl Sulphate BP/USP 0.1%) in per 1 hole, it is soluble that cell is become.To wherein adding 2M hydrochloric acid 15 μ L, 40 μ L are transferred among the Luma-plate (Packard corporate system) with this solution, at room temperature place a night, make solvent evaporation thus.Radioactivity with the sample on Topcount (Packard corporate system) assay plate.The value that to deduct basic intake from the contrast intake utilizes software for calculation (ELfit ver.3) to calculate the test compound concentration (IC that intake can be suppressed as 100% at 50% o'clock from concentration-inhibition curve ₅₀Value).Its result shows that compound exhibits of the present invention goes out significant SGLT2 restraining effect.Representative compounds of the present invention is to the IC of the inhibition of SGLT2 ₅₀Value is shown in the table.

[table 11]

Table 11

Test compound	IC ₅₀Value (nM)	Test compound	IC ₅₀Value (nM)
				Embodiment 1	61?	Embodiment 59	8.9?
Embodiment 2	111?	Embodiment 62	7.1?
				Embodiment 8	7?	Embodiment 64	6.6?
Embodiment 11	14?	Embodiment 68	18?
				Embodiment 12	18?	Embodiment 69	5.1?
Embodiment 25	31?	Embodiment 70	7.4?
				Embodiment 42	7.7?	Embodiment 73	11?
Embodiment 44	16?	Embodiment 74	14?
				Embodiment 55	17?	?	?

The invention provides a kind of compounds or its pharmaceutically useful salt that demonstrates good inhibition SGLT2 active function.Compound of the present invention can be used as the prevention or the curative of diabetes, diabetes relative disease or diabetic complication.

Claims

1. by the compound of formula (I) expression or their pharmaceutically useful salt:

In the formula,

N is 0, and perhaps n is 1, and A is-O-;

R ⁶And R ⁷Be hydrogen atom independently of one another;

M is 1;

Q is selected from the Q that is expressed from the next ¹～Q ⁵In the 6-unit carbocyclic ring of replacement:

R ¹, R ², R ³, and R ⁴Be hydroxyl independently of one another;

R ⁵Be selected from hydrogen atom or hydroxyl;

Ar ¹Be phenylene, inferior thienyl or pyridylidene, these groups can be replaced by the Rb more than 1;

Ar ²Be the phenyl that can be replaced by the Rb more than 1;

Rb is selected from halogen atom, C independently of one another ₁-C ₆Alkyl, C ₃-C ₈Cycloalkyl, C ₁-C ₆Alkoxyl group, C ₁-C ₆Alkylthio and C ₁-C ₆Alkenyl.

2. described compound of claim 1 or their pharmaceutically useful salt, wherein, n is 1.

3. described compound of claim 2 or their pharmaceutically useful salt, wherein, at Ar ¹On, substituting group-(CR ⁶R ⁷) _m-Ar ²Being bonded to bonding has on the adjacent annular atoms of the annular atoms of substituent A.

4. described compound of claim 1 or their pharmaceutically useful salt, wherein, n is 0.

5. described compound of claim 4 or their pharmaceutically useful salt, wherein, at Ar ¹On, substituting group-(CR ⁶R ⁷) _m-Ar ²Being bonded to from bonding has on the 2nd annular atoms that the annular atoms of Q leaves.

6. be selected from following compound, perhaps their pharmaceutically useful salt:

[2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[1S, 2R, 3R, 4R, 6S]-4-methylol-6-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2, the 3-triol;

[2-(4-cyclopentyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-benzyl chloride base) phenyl]-5a-carbon-β-D-glucopyranoside;

(2-benzyl phenyl)-5a-carbon-β-D-glucopyranoside;

[2-(4-isopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclopropyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-n-propyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methyl sulfane base benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[3-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-p-methoxy-phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-6-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-4-fluorophenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[5-fluoro-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-luorobenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3, the 4-dimethoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[5-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-ethoxy benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-tertiary butyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[3-methoxyl group-2-(4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-3-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-fluoro-4-methoxy-benzyl) phenyl]-5a-carbon-α-D-glucopyranoside;

[4-(4-cyclopropyl benzyl) pyridin-3-yl]-5a-carbon-β-D-glucopyranoside;

[2-(4-vinyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-fluoro-4-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxyl group-3-methyl-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(3-chloro-4-methoxy-benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclobutyl benzyl) phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-methoxy-benzyl)-5-aminomethyl phenyl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl) thiene-3-yl-]-5a-carbon-β-D-glucopyranoside;

[2-(4-cyclopropyl benzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside;

[2-(4-Ethylbenzyl)-5-thiotolene-3-yl]-5a-carbon-β-D-glucopyranoside;

(1R, 2R, 3S, 4R, 5R)-1-[5-(4-Ethylbenzyl)-2-p-methoxy-phenyl]-5-(methylol) hexamethylene-1,2,3, the 4-tetrol;

(1R, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol; With

(1S, 2R, 3S, 4R, 5R)-and 5-methylol-1-[3-(4-methoxy-benzyl) phenyl] hexamethylene-1,2,3, the 4-tetrol.

7. the compound of claim 1-6 described in each is used to prepare the purposes of medicine, diabetic complication or obesity that described medicine is used to prevent or treat diabetes, causes because of hyperglycemia.

8. the purposes of claim 7, wherein, described diabetes are type 1 diabetes or diabetes B.

9. pharmaceutical composition wherein contains the diabetic complication that is useful on prevention or treatment diabetes, causes because of hyperglycemia or each described compound of claim 1～6 of obesity.