CN101045678B - Method for producing hexahydrolupulicone - Google Patents
Method for producing hexahydrolupulicone Download PDFInfo
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- CN101045678B CN101045678B CN200610066047A CN200610066047A CN101045678B CN 101045678 B CN101045678 B CN 101045678B CN 200610066047 A CN200610066047 A CN 200610066047A CN 200610066047 A CN200610066047 A CN 200610066047A CN 101045678 B CN101045678 B CN 101045678B
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- lupulone
- hexahydrolupulon
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- humulone
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Abstract
A process for preparing hexahydrolupulone includes such steps as dissolving the extract of hop in the alkaline aqueous solution of alcohol, separating out humulone and lupulone, filling CO2 gas, separating coarse lupulone recrystallizing in n-hexane, dissolving in reactive medium, adding catalyst Pd/C, filling H2, hydroreacting, filtering, concentrating the filtrate, laying aside, cooling for crystallizing, filtering to obtain coarse hexahydrolupulone, and recrystallizing in n-hexane. It can be used in food for antiseptic, bacteria-suppressing and antioxidizing purposes.
Description
Technical field
The present invention relates to a kind of production method of hexahydrolupulon, more specifically, the present invention relates to a kind of by liquid, subcritical or supercritical CO
2Hops Extract prepares the method for hexahydrolupulon.
Background technology
Hops Extract is when producing tetrahydro-iso-humulone, and lupulone is wherein thrown aside as by product usually.As Chinese patent application numbers 94100149.0,200410073602.6, lupulone has extraordinary bacteriostatic activity, but it is oxidation very easily, preserve difficulty, and the hydrogenated products hexahydrolupulon of lupulone not only has extraordinary chemical stability, and is still keeping extraordinary antibacterial and anti-oxidant activity.Because the catalytic hydrogenation reaction of lupulone is very responsive to reaction conditions, often be accompanied by complicated hydrogenolysis in the time of hydrogenation and take place, cause the yield of hexahydrolupulon very low, therefore do not see that commercial product is arranged.
Summary of the invention
The present invention is in order to solve in the prior art when producing tetrahydro-iso-humulone, the lupulone that exists is thrown aside as by product usually, causes product single, the shortcoming that cost is high, and a kind of compound of new antibacterial anti-oxidant easy preservation is provided, technical scheme of the present invention has been proposed.
A kind of method of producing hexahydrolupulon that the present invention proposes, may further comprise the steps: (1) is dissolved in Hops Extract in the alkaline ethanol aqueous solution, separate insolubles in the medicinal extract, after from medicinal extract, isolating humulone and lupulone simultaneously, after this solution with water dilution, make the mixing solutions of humulone and lupulone; Then with CO
2Gas feeds in the mixing solutions of humulone and lupulone, and lupulone crystallization is wherein separated out, and isolates the crude product of lupulone; With the crude product of this lupulone normal hexane recrystallization, can obtain the purification thing of lupulone, this purification thing promptly can be used for the raw material of lupulone catalytic hydrogenation reaction.(2) get a certain amount of lupulone, in the adding reaction medium it is dissolved fully, mixing.In the hydrogenation still, add the Pd/C catalyzer, the above-mentioned reaction soln that mixes is poured in the still, after the reactor sealing is installed, after going out air in the reactor with nitrogen replacement, feed hydrogen and carry out hydrogenation reaction, after reaction finishes, after with nitrogen the hydrogen exchange in the reactor being come out earlier.(3) with behind the hydrogenation liquid filtering separation Pd/C catalyzer wherein, filtrate is concentrated, place, cool off, there is mass crystallization to separate out, filter, obtain the crude product of hexahydrolupulon.(4) with the crude product of hexahydrolupulon behind the normal hexane recrystallization, obtain purified hexahydrolupulon product.
Described hop extract comprises liquid CO
2Hop extract, subcritical or supercritical CO
2Hop extract.
Alkaline solution described in the step (1) is preferably potassium hydroxide, sodium hydroxide, salt of wormwood, aqueous sodium carbonate, this solution contains 5%～20% water, the consumption of KOH or NaOH aqueous ethanolic solution is 0.5～1 times of medicinal extract amount, and the mole number of KOH or NaOH consumption is 1.1～1.8 times of soft resin total mole number in the medicinal extract.
Step (1) is preferably being carried out below 50 ℃.
At the described reaction medium of step (3) is ethanol-water solution, and wherein the volume ratio of second alcohol and water is 1～20: 1, and preferred ethanolic soln concentration is 95%, and consumption is 20 times of lupulone weight; Selected catalyzer is Pd/C, and Pt/C, or nickel catalyzator, consumption are 5～10% of lupulone weight, and wherein the Pd/C catalyst consumption is preferably 10% of lupulone weight.The hydrogenation technique condition of step (3) is: the hydrogen gauge pressure is 0.5～60kg/cm
2, the pH value of solution is 6～12, and temperature is 30～140 ℃, and the reaction times is 4～15 hours, and the amounts of hydrogen of reaction consumes is 2～4 times of lupulone mole number.
Below each step of the present invention is described in detail.
Step (1) is for obtaining the process of high purity lupulone.This sepn process majority in document in the past is directly with the lupulone in the alkali lye dissolving hop extract, be the alkali lye of 0.05%-0.5% with concentration earlier, the washing hop extract is to remove acidic impurities wherein, then with the lupulone in the alkali lye dissolving hop extract.The present invention is dissolved in Hops Extract in the alkaline ethanol aqueous solution, separates insolubles in the medicinal extract, from medicinal extract, isolate humulone and lupulone simultaneously after, make the mixing solutions of humulone and lupulone; Then with CO
2Gas feeds in the mixed solution of humulone and lupulone, and lupulone crystallization is wherein separated out, and isolates the crude product of lupulone; With the crude product of this lupulone normal hexane recrystallization, can obtain the purification thing of lupulone, this purification thing promptly can be used for the raw material of lupulone catalytic hydrogenation reaction.
Step (2) is the lupulone catalytic hydrogenation.Lupulone purification thing to obtain in the above-mentioned steps (1) is dissolved in the reaction medium aqueous ethanolic solution, directly carries out catalytic hydrogenation.Adopt Pd/C to make catalyzer, make the thick product of hexahydrolupulon.After hydrogenation reaction is finished, filter or solid substance (being mainly catalyzer) is removed in centrifugation, and with 95% washing with alcohol solid substance 1-2 time, washings is integrated with the solution of thick product.
Step (3) is a last handling process.Above-mentioned thick product solution is poured this concentrated solution in the container into cooling after placing and concentrating most of solvent of removing wherein on the rotatory evaporator again.Under agitation slowly add a certain amount of distilled water then, have small amount of crystalline to separate out this moment, and this solution is cooled off, places a few hours, promptly has mass crystallization to separate out, and filters, and obtains the crude product of hexahydrolupulon.
Step (4) is the product purification process.The crude product of hexahydrolupulon behind the normal hexane recrystallization, is obtained purified hexahydrolupulon product.Also can select for use the methyl alcohol or the alcoholic acid aqueous solution to come recrystallization.
Sanitas, fungistat and antioxidant that the hexahydrolupulon that the present invention produces can be used for food use.
Production method of the present invention has the following advantages:
(1) since the by product that will abandon originally as raw material, production cost is low.
(2) hexahydrolupulon of method production of the present invention has extraordinary antibacterial and anti-oxidant activity.
(3) method of the present invention adopts the cooling process product, and advantages of good crystallization has been removed impurity wherein, and operating process is simple, has improved the purity of product, the product yield height.
Embodiment
Adopt the mode of embodiment to explain the present invention particularly below, but the present invention is not limited to embodiment.
Embodiment 1:
1.1 the separation and purification of lupulone
Hops Extract 100g (wherein humulone content is 59.7%, and lupulone content is 18.6%) is dissolved in (KOH that contains 12.5g in this solution) in the 50ml alkaline ethanol aqueous solution, left standstill after the dissolving one hour, separate insolubles in the medicinal extract.In the isolated alkaline ethanol aqueous solution that contains humulone and lupulone, add the 450ml distilled water diluting, make the mixing solutions of humulone and lupulone; Then with CO
2Gas feeds in the mixed solution of humulone and lupulone, and when the pH value of solution reached 8.5 left and right sides, lupulone wherein began crystallization and separates out.Stop to feed CO
2, continue to stir 40-60min, leave standstill, from solution, filter to isolate the crude product 22.3g of lupulone, the crude product of this lupulone is analyzed through HPLC, and the content of lupulone is 75.9%.The crude product of this lupulone with normal hexane recrystallization 1 time, can be obtained content and be the purification thing 16.8g of 95.8% lupulone, and the total yield of lupulone is 86.5%.This purification thing promptly can be used for the raw material of lupulone catalytic hydrogenation reaction.
1.2. lupulone catalytic hydrogenation
With the lupulone purification thing of resulting 16.8g in the above-mentioned reaction, the alkaline ethanol solution (this solution is 11 with the KOH adjust pH) that adds the reaction medium 95% of 330ml dissolves it fully, mixing.In the hydrogenation still, add the Pd/C catalyzer of 1.6g10%, the above-mentioned reaction soln that mixes is poured in the still, after the reactor sealing is installed, open inlet mouth, connect N
2Steel cylinder feeds N
2, open purging valve simultaneously, displace the air in the reactor, close purging valve behind the 10min, stop logical N
2, inlet mouth is switched to H
2Steel cylinder is opened H
2Intake valve is opened purging valve once more, displaces the nitrogen in the reactor, closes purging valve behind the 5min, make hydrogen pressure in the reactor rise to required pressure after, close intake valve.Connecting power supply, open temperature controlled switch and agitator, is 6kg/cm in the hydrogen pressure gauge pressure
2, temperature of reaction is to make its reaction under 50 ℃ the reaction conditions.Hydrogen pressure decline 0.5kg/cm in reactor
2The time, open hydrogen inlet again, hydrogen make-up is to the reaction pressure of setting.Reaction stops the back end to inhaling hydrogen, and the reaction times is about 6 hours.After reaction finishes, after with nitrogen the hydrogen exchange in the reactor being come out earlier, open reactor again, reaction solution is taken out further handle.This reaction solution is analyzed through HPLC, and wherein the content of hexahydrolupulon is 4.1%, and the total conversion rate of lupulone is 84.1%.
1.3 the purifying of hexahydrolupulon
Behind above-mentioned hydrogenation liquid filtering separation Pd/C catalyzer wherein, with filtrate place on the rotatory evaporator concentrate most of solvent of removing wherein after, the concentrated solution that remains about about 50ml is poured in the 200ml beaker, under agitation slowly add 20ml distilled water, have small amount of crystalline to separate out this moment, this solution put in the refrigerator placed two hours, promptly has mass crystallization to separate out, filter, obtain the crude product 15.6g of hexahydrolupulon.The hexahydrolupulon that this is thick obtains content and is 99.5% hexahydrolupulon 11.9g behind 2 recrystallizations of normal hexane, the yield of hexahydrolupulon is 73.6%.After measured, this crystalline melting range is 91-93 ℃, and is consistent with literature value.
Embodiment 2
Draw kind of bacterium liquid with aseptic dropper and put into sterile petri dish, inject about 15ml sterilization molten nutrient agar, the mixing postcooling is frozen into and contains the bacterium flat board, with the sample of hexahydrolupulon with a small amount of sterilized dissolve with ethanol, the alkali lye that is 11-13 with sterilized pH value is mixed with 500ppm, 250ppm, four series concentration of 125ppm, 32ppm respectively then, measure under each concentration antibacterial circle diameter size respectively to different strain, observe antibacterial situation, determine fungistatic effect and minimum inhibitory concentration.
The table hexahydrolupulon is to the mensuration of the Mlc of common food spoilage bacterium
| 500ppm | 250ppm | 125ppm | 32ppm | |
| The listeria bacteria | 17.3 | 11.7 | 11.0 | 7.9 |
| Staphylococcus aureus | 17.0 | 9.6 | 9.3 | 7.8 |
| Bacillus megaterium | 7.1 | - | - | - |
| Intestinal bacteria | 16.7 | 12.3 | - | - |
| Proteus vulgaris | 14.0 | 14.3 | 10.3 | - |
| 500ppm | 250ppm | 125ppm | 32ppm | |
| Pseudomonas fluorescens | 19.0 | 11.3 | 8.5 | 8.5 |
Annotate: the data of being given in the table are the diameter of inhibition zone, the mm of unit, the no fungistatic effect of "-" expression.
Claims (1)
1. method of producing hexahydrolupulon, it is characterized in that it may further comprise the steps: (1) is dissolved in Hops Extract in the alkaline ethanol aqueous solution, separate insolubles in the medicinal extract, after from medicinal extract, isolating humulone and lupulone simultaneously, with this solution with water dilution, make the mixing solutions of humulone and lupulone; Then with CO
2Gas feeds in the mixing solutions of humulone and lupulone, and lupulone crystallization is wherein separated out, and isolates the crude product of lupulone; With the crude product of this lupulone normal hexane recrystallization, obtain the purification thing of lupulone, this purification thing promptly can be used for the raw material of lupulone catalytic hydrogenation reaction; (2) get a certain amount of lupulone, in the adding reaction medium it is dissolved fully, mixing; In the hydrogenation still, add the Pd/C catalyzer, the above-mentioned reaction soln that mixes is poured in the still, after the reactor sealing is installed, after going out air in the reactor with nitrogen replacement, feed hydrogen and carry out hydrogenation reaction, after reaction finishes, after with nitrogen the hydrogen exchange in the reactor being come out earlier; (3) with behind the hydrogenation liquid filtering separation Pd/C catalyzer wherein, filtrate is concentrated, place, cool off, there is mass crystallization to separate out, filter, obtain the crude product of hexahydrolupulon; (4) with the crude product of hexahydrolupulon behind the normal hexane recrystallization, obtain purified hexahydrolupulon product.
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| CN200610066047A CN101045678B (en) | 2006-03-28 | 2006-03-28 | Method for producing hexahydrolupulicone |
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| CN200610066047A CN101045678B (en) | 2006-03-28 | 2006-03-28 | Method for producing hexahydrolupulicone |
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| CN101045678B true CN101045678B (en) | 2010-05-26 |
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| CN101967177A (en) * | 2010-09-17 | 2011-02-09 | 华中农业大学 | Extract and method for extracting tea saponin from oil-tea seed residue |
| CN102870874B (en) * | 2012-10-11 | 2014-03-12 | 甘肃农业大学 | Natural bacteriostatic agent for muskmelons |
| CN104116120B (en) * | 2014-07-30 | 2016-05-04 | 谢松芬 | A kind of antistaling agent made from plant waste |
| CN104447264B (en) * | 2014-11-08 | 2016-08-17 | 商洛学院 | A kind of method extracting separation .beta.-bitter acid from Flos lupuli (Flos Humuli Lupuli) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4342791A (en) * | 1979-05-24 | 1982-08-03 | Brewing Patents Limited | Method of purifying iso-α-acids |
| US5827895A (en) * | 1996-02-27 | 1998-10-27 | Regents Of The University Of Minnesota | Hexahydrolupulones useful as anticancer agents |
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2006
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4342791A (en) * | 1979-05-24 | 1982-08-03 | Brewing Patents Limited | Method of purifying iso-α-acids |
| US5827895A (en) * | 1996-02-27 | 1998-10-27 | Regents Of The University Of Minnesota | Hexahydrolupulones useful as anticancer agents |
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