CN105481711B - Hydroxy-beta-sanshool monomer preparation method - Google Patents
Hydroxy-beta-sanshool monomer preparation method Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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Abstract
The invention provides a hydroxy-beta-sanshool monomer preparation method and belongs to the technical field of natural drug extraction. The preparation method effectively realizes extraction of a high-concentration hydroxy-beta-sanshool monomer from a Chinese prickly ash raw material. The preparation method comprises 1, extracting a hydroxysanshool mixture, 2, carrying out enrichment and pressure reduction condensation on the hydroxysanshool mixture to obtain hydroxysanshool mixture extract, 3, transforming hydroxy-beta-sanshool to improve hydroxy-beta-sanshool content of the hydroxysanshool mixture extract solution, 4, purifying the hydroxy-beta-sanshool to obtain a hydroxy-beta-sanshool monomer with purity of 70% or more, and 5, carrying out recrystallization to obtain a hydroxy-beta-sanshool monomer with purity of 98% or more. The preparation method is mainly used for preparing the hydroxy-beta-sanshool monomer.
Description
Technical field
The invention belongs to natural drug extractive technique field.
Background technology
Pericarpium Zanthoxyli (Zanthoxylum L.) is Rutaceae (Rutaceae) Zanthoxylum (ZanthoxylumL inn) plant.Flower
Green pepper fruit is one of China's traditional " eight big flavoring agent ", and its pungent numb taste is main flavor characteristic, is also most important quality
Index.In addition Pericarpium Zanthoxyli is also China's conventional Chinese medicine, can be used to treat vomiting, diarrhoea, ascariasis etc., and external can treat eczema pain
Itch, promoting blood circulation to remove blood stasis, and the aspect such as treatment and analgesia to cardiovascular system diseases, calmness, antiinflammatory, antibacterial has obvious medicine
Reason activity.
Fagaramide is mostly chain unsaturated fatty acid amide structure, wherein being Pericarpium Zanthoxyli fiber crops taste by representative of sanshool
Main component, acts on TRPV1, TRPA1 etc. is stimulated.In Pericarpium Zanthoxyli amide substance be mainly hydroxyl-alpha-sanshool and hydroxyl-
β-sanshool, but because hydroxyl-alpha-sanshool is unstable, standard substance requirement is not met, do not possess as numb taste reference
Condition.Hydroxy-beta-sanshool is less slightly relative to hydroxyl-alpha-Pericarpium Zanthoxyli cellulose content, but relatively stable, can be prepared into Pericarpium Zanthoxyli
Numb taste reference.Hydroxy-beta-sanshool, is that Pericarpium Zanthoxyli produces the topmost activity of numb taste mechanism of action with narcoticness acid
One of compound, is present in the fruit of rutaceae Pericarpium Zanthoxyli and Fructus Zanthoxyli, and its molecular formula is C16H25NO2.High woods good fortune et al. was once
Chinese patent application, entitled " manufacture method of the extract of hydroxyl sanshool " (Shen are disclosed on November 13rd, 2012
Please publication No.：CN 201210452421.9), invent the extracting method of the hydroxyl sanshool mixture of low content.Zhao Zhifeng etc.
People once disclosed Chinese patent application on 05 31st, 2012, entitled " a kind of that hydroxyl sanshool is extracted from Fructus Zanthoxyli oil
Method " (application publication number：CN 201210175527.9), invent the method for extracting hydroxyl sanshool mixture.It is relevant at present
The extraction preparation method of numb-taste components mainly uses supercritical CO2Extract and separate goes out numb-taste components sanshool, carries
Take thing and be mostly xanthoxylum oleoresin or quintessence oil, be only capable of the hydroxyl sanshool for obtaining mixing, and purification can not be efficiently separating and obtained
The hydroxy-beta of Pericarpium Zanthoxyli-sanshool monomer, largely limits the research and application of numb-taste components.
The content of the invention
It is an object of the invention to provide a kind of preparation method of hydroxy-beta-sanshool monomer, it can be effectively former in Pericarpium Zanthoxyli
Hydroxy-beta-sanshool monomer is extracted in material.
The object of the invention another purpose is to provide a kind of preparation method of hydroxy-beta-sanshool monomer, and it can be effectively
Prepare the higher hydroxy-beta-sanshool monomer of purity.
The purpose of the present invention is achieved through the following technical solutions：Extraction, enrichment including subject matter, preparation technology
Step is as follows：
The extraction of step one, hydroxyl sanshool mixture
Pericarpium Zanthoxyli peel crushing will be dried, Extraction solvent volume fraction is the aqueous solution of more than 85% lower alcohol to Pericarpium Zanthoxyli
Peel powder carries out merceration extraction, and liquid ratio is 1:5~1:10, extraction time is 48h, is extracted 2~3 times, merges lixiviating solution, is abandoned
Medicinal residues, lixiviating solution concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is the 1/5~1/4 of lixiviating solution, obtains hydroxyl sanshool mixing
Thing；
The enrichment of step 2, hydroxyl sanshool mixture
The hydroxyl sanshool mixture of step one gained is diluted with water to into low-alcohol solution volume fraction 10%~20%,
Isolated and purified by non-polar polystyrene type macroporous adsorbent resin column chromatography, be dried Pericarpium Zanthoxyli fruit weight and macroporous absorption
Resin volume ratio is 1Kg:0.5~1L, dynamic adsorption loading, adsorption rate control is in 2.0BV~3.0BV per hour, absorption
After finishing, first respectively with the water of 2.0BV~3.0BV and 50%~60% low-alcohol solution eluting remove impurity, then with 2.5BV~
The low-alcohol solution eluting of the 85%~95% of 4.0BV, collects eluent, and concentrating under reduced pressure obtains hydroxyl sanshool mixture extractum.
The conversion of step 3, hydroxy-beta-sanshool
Due in the hydroxyl sanshool mixture extractum obtained by step 2 hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, needs to be converted by the reaction of double bond cis-trans isomerism, and hydroxyl sanshool mixture extractum organic solvent is dissolved, and adds
Iodine carries out double bond cis-trans isomerization reaction as catalyst, after reaction balance, part of hydroxyl-α-sanshool change into hydroxy-beta-
Sanshool, reaction equation is as follows：
Content of the hydroxy-beta-sanshool in hydroxyl sanshool mixture extractum solution is improve after reaction.
The purification of step 4, hydroxy-beta-sanshool
Step 3 gained hydroxyl sanshool mixture extractum solution is positioned over into freezing crystallize in refrigerator, filtration drying
Obtain hydroxy-beta-sanshool monomer that purity reaches more than 70%；
Low-alcohol solution described in step one is methanol, one or more mixture of ethanol.
Non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
Organic solvent described in step 3 is one or more the mixture in petroleum ether, acetone, ethyl acetate.
The purpose of the present invention another purpose is achieved through the following technical solutions：A kind of hydroxy-beta-sanshool list
The preparation method of body, including repeat above-mentioned one~step 3 the step of pass through：
The extraction of step one, hydroxyl sanshool mixture
Pericarpium Zanthoxyli peel crushing will be dried, Extraction solvent volume fraction is the aqueous solution of more than 85% lower alcohol to Pericarpium Zanthoxyli
Peel powder carries out merceration extraction, and liquid ratio is 1:5~1:15, extraction time is 48h, is extracted 2~3 times, merges lixiviating solution, is abandoned
Medicinal residues, lixiviating solution concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is the 1/5~1/4 of lixiviating solution, obtains hydroxyl sanshool mixing
Thing.
The enrichment of step 2, hydroxyl sanshool mixture
It is 10%~20% that the hydroxyl sanshool mixture of step one gained is diluted with water to into lower alcohol volume fraction, is led to
Cross non-polar polystyrene type macroporous adsorbent resin column chromatography to be isolated and purified, be dried Pericarpium Zanthoxyli fruit weight and macroporous absorption tree
Fat volume ratio is 1Kg:0.5L~1L, dynamic adsorption loading, adsorption rate is controlled in 2.0BV~3.0BV per hour, has been adsorbed
Bi Hou, first respectively with the water of 2.0BV~3.0BV and 50%~60% low-alcohol solution eluting remove impurity, then with 2.5BV~
The low-alcohol solution eluting of the 85%-95% of 4.0BV, collects eluent, and concentrating under reduced pressure obtains hydroxyl sanshool mixture extractum.
The conversion of step 3, hydroxy-beta-sanshool
Due in the hydroxyl sanshool mixture extractum obtained by step 2 hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, needs to be converted by the reaction of double bond cis-trans isomerism, and hydroxyl sanshool mixture extractum organic solvent is dissolved, and adds
Iodine carries out double bond cis-trans isomerization reaction as catalyst, after reaction balance, part of hydroxyl-α-sanshool change into hydroxy-beta-
Sanshool, reaction equation is as follows：
Content of the hydroxy-beta-sanshool in hydroxyl sanshool mixture extractum solution is improve after reaction.
The purification of step 4, hydroxy-beta-sanshool
The hydroxyl sanshool mixture extractum solution that step 3 is obtained is positioned over freezing crystallize in refrigerator, crosses and is filtered dry
It is dry to obtain hydroxy-beta-sanshool monomer that purity reaches more than 70%.
Step 5, recrystallization
Hydroxy-beta-sanshool mixture extractum organic solvent is dissolved, freezing is placed, crystallize, filtration drying obtains pure
Degree reaches more than 98% hydroxy-beta-sanshool monomer.
Lower alcohol described in step one is one or more the mixture in methanol, ethanol.
Non-polar polystyrene type macroporous resin model described in step 2 is D101, AB-8, HP20.
Organic solvent described in step 3 is one or more the mixing in petroleum ether, acetone, ethyl acetate
Thing.
Organic solvent described in step 5 is one or more the mixing in petroleum ether, acetone, ethyl acetate
Thing.
Advantage compared with prior art and effect：
First, the inventive method obtains highly purified by extracting, being enriched with, convert, by five steps of purification and recrystallization
Hydroxy-beta-sanshool monomer.Whole preparation process mild condition, maximum temperature is less than 60 DEG C, it is ensured that hydroxy-beta-sanshool
Stability, it is and high income, easy to operate, low to operator's technical requirements, be adapted to industrialization promotion.
2nd, the product purity obtained by the present invention is high, and obtained hydroxy-beta-sanshool monomer purity is up to more than 98%.Fill out
Blank of the hydroxy-beta-sanshool as reference in current Pericarpium Zanthoxyli fiber crops degree detection and Pericarpium Zanthoxyli Quality Detection is mended.
3rd, the equipment that the inventive method is used is mainly, chromatographic column during column chromatography, rotary evaporation during concentrating under reduced pressure
Cheap, the low production cost of instrument, chromatographic column and Rotary Evaporators.
Description of the drawings
Fig. 1 be the embodiment of the present invention 5 obtain hydroxy-beta-sanshool monomer efficient liquid phase chromatographic analysis figure, t=in figure
17.52min peaks are hydroxy-beta-sanshool.
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of hydroxy-beta-sanshool monomer that the embodiment of the present invention 5 is obtained.
Fig. 3 is the carbon-13 nmr spectra figure of hydroxy-beta-sanshool monomer that the embodiment of the present invention 5 is obtained.
Specific embodiment
Embodiment 1
A kind of preparation method of hydroxy-beta-sanshool monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take and be dried Pericarpium Zanthoxyli peel 2kg and crush, with aqueous solution that volume fraction is 95% ethanol extraction 48h, liquid ratio is 1：
10, extract 3 times, merge lixiviating solution, medicinal residues are abandoned, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, the volume of concentrated solution
For the 1/5 of lixiviating solution, hydroxyl sanshool mixture i.e. fagaramide crude product is obtained.
(2) the enrichment of hydroxyl sanshool mixture
It is 20% that by step, (2) the fagaramide crude product of gained is diluted with water to volume fraction of ethanol, by D101 type macropores
Adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:1L, moves
State adsorbs loading, and adsorption rate control after absorption is finished, first uses respectively the water and 50% ethanol of 2.0BV in 2.0BV per hour
Eluant solution remove impurity, then the ethanol solution eluting of 85% with 2.5BV, collect eluent, and concentrating under reduced pressure is obtained at a temperature of 50 DEG C
Extractum 70g.
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so need to carry out double-bond isomerism reaction conversion, with petroleum ether acetone (1:1) mixed solution dissolving hydroxyl sanshool mixture
Extractum, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.55 in the solution by HPLC detections:1, adding should
0.9% iodine of solution carries out double-bond isomerism reaction as catalyst, and after 20 DEG C of reaction 9h, part of hydroxyl-α-sanshool is changed into
Hydroxy-beta-sanshool, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution by HPLC detections:2.97.
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 18h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 2.0g that purity reaches 78.2%.
Embodiment 2
A kind of preparation method of hydroxy-beta-sanshool monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take be dried Pericarpium Zanthoxyli peel 2kg crush, with flooding 48h that volume fraction is 85% ethanol, liquid ratio is 1：8, carry
Take 3 times, merge lixiviating solution, abandon medicinal residues, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, and the volume of concentrated solution is extraction
The 1/5 of liquid, obtains hydroxyl sanshool mixture i.e. fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
It is 20% that by step, (2) the fagaramide crude product of gained is diluted with water to volume fraction of ethanol, big by HP-20 types
Macroporous adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:
0.7L, dynamic adsorption loading, adsorption rate control in 2.5BV per hour, after absorption is finished, first respectively with the water of 2.5BV and
55% ethanol solution eluting remove impurity, then the ethanol solution eluting of 85% with 3BV, collect eluent, subtract at a temperature of 50 DEG C
Pressure is concentrated to give extractum 65g.
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so need to carry out double-bond isomerism reaction conversion, with petroleum ether acetone (2:1) mixed solution dissolving hydroxyl sanshool mixture
Extractum, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.31 in solution by HPLC detections:1, add solution
0.1% iodine carry out double-bond isomerism reaction as catalyst, after 35 DEG C of reaction 12h, part of hydroxyl-α-sanshool changes into hydroxyl
Base-β-sanshool, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution by HPLC detections:2.72.
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 24h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 1.7g that purity reaches 72.3%.
Embodiment 3
A kind of hydroxy-beta-sanshool method for preparing monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take be dried Pericarpium Zanthoxyli peel 2kg crush, with flooding 48h that volume fraction is 90% methanol, liquid ratio is 1：10, carry
Take 3 times, merge lixiviating solution, abandon medicinal residues, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, and the volume of concentrated solution is extraction
The 1/5 of liquid, obtains hydroxyl sanshool mixture i.e. fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
It is 15% that by step, (2) the fagaramide crude product of gained is diluted with water to methanol volume fraction, big by AB--8 types
Macroporous adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:1L,
Dynamic adsorption loading, adsorption rate control after absorption is finished, first uses respectively the water and 55% first of 2.5BV in 2.5BV per hour
Alcoholic solution eluting remove impurity, then the methanol solution eluting of 85% with 3BV, collect eluent, and concentrating under reduced pressure is obtained at a temperature of 50 DEG C
Extractum 58g.
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so needing to carry out double-bond isomerism reaction conversion, with ethyl acetate solution hydroxyl sanshool mixture extractum is dissolved, and is passed through
HPLC detections understand that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.41 in the solution:1, add the 0.5% of solution
Iodine carries out double-bond isomerism reaction as catalyst, and after 40 DEG C of reaction 15h, part of hydroxyl-α-sanshool changes into hydroxy-beta-Pericarpium Zanthoxyli
Element, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution by HPLC detections:2.9.
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 36h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 1.5g that purity reaches 71.0%.
Embodiment 4
A kind of preparation method of hydroxy-beta-sanshool monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take be dried Pericarpium Zanthoxyli peel 2kg crush, with volume fraction be pure methanol extract 48h, liquid ratio is 1: 8, extract 3 times,
Merge lixiviating solution, abandon medicinal residues, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, and the volume of concentrated solution is the 1/ of lixiviating solution
5, obtain hydroxyl sanshool mixture i.e. fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
It is 20% that by step, (2) the fagaramide crude product of gained is diluted with water to methanol volume fraction, by D101 type macropores
Adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:0.7L,
Dynamic adsorption loading, adsorption rate control after absorption is finished, first uses respectively the water and 55% first of 2.5BV in 2.5BV per hour
Alcoholic solution eluting remove impurity, then the methanol solution eluting of 85% with 3BV, collect eluent, and concentrating under reduced pressure is obtained at a temperature of 50 DEG C
Extractum 65g.
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so need to carry out double-bond isomerism reaction conversion, with petroleum ether acetone (2:1) mixed solution dissolving hydroxyl sanshool mixture
Extractum, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.31 in the solution by HPLC detections:1, adding should
0.05% iodine of solution carries out double-bond isomerism reaction as catalyst, after 20 DEG C of reaction 10h, part of hydroxyl-α-sanshool conversion
Into hydroxy-beta-sanshool, understand that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution by HPLC detections:
2.72。
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 20h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 1.7g that purity reaches 72.3%.
Embodiment 5
A kind of preparation method of hydroxy-beta-sanshool monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take be dried Pericarpium Zanthoxyli peel 10kg crush, with volume fraction be pure methanol extract 48h, liquid ratio is 1：5, extract 3 times,
Merge lixiviating solution, abandon medicinal residues, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, and the volume of concentrated solution is the 1/ of lixiviating solution
4, obtain hydroxyl sanshool mixture i.e. fagaramide crude product.
(2) the enrichment of hydroxyl sanshool mixture
It is 10% that by step, (1) the fagaramide crude product of gained is diluted with water to methanol volume fraction, by AB-8 type macropores
Adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:0.5L,
Dynamic adsorption loading, adsorption rate control after absorption is finished, first uses respectively the water and 60% first of 3.0BV in 3.0BV per hour
Alcoholic solution eluting remove impurity, then the methanol solution eluting of 90% with 3.0BV, collect eluent, the concentrating under reduced pressure at a temperature of 50 DEG C
Obtain extractum 150g；
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so need to carry out double-bond isomerism reaction conversion, with petroleum ether acetone (0.5:1) mixed solution dissolving hydroxyl sanshool mixing
Thing extractum, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.47 in the solution by HPLC detections:1, add
1% iodine of the solution carries out double-bond isomerism reaction as catalyst, and after 25 DEG C of reaction 8h, part of hydroxyl-α-sanshool is changed into
Hydroxy-beta-sanshool, hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution:2.87.
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 48h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 13g that purity reaches 79%；
(5), by step (4) gained hydroxy-beta-sanshool monomer acetone solution, 8h is placed in freezing, and crystallize, filtration drying obtains
Hydroxy-beta-sanshool monomer 8.1g, using high phase liquid chromatograph (HPLC) hydroxyl β-sanshool monomer that this example is obtained is detected
Purity, measures its purity for 99.4%.
Embodiment 6
A kind of preparation method of hydroxy-beta-sanshool monomer, comprises the steps：
(1) the extraction of hydroxyl sanshool mixture
Take and be dried Pericarpium Zanthoxyli peel 10kg and crush, with water alcohol that volume fraction is 95% ethanol extraction 48h, liquid ratio is 1：
15, extract 3 times, merge lixiviating solution, medicinal residues are abandoned, lixiviating solution concentrating under reduced pressure at a temperature of 50 DEG C obtains concentrated solution, the volume of concentrated solution
For the 1/4 of lixiviating solution, hydroxyl sanshool mixture i.e. fagaramide crude product is obtained.
(2) the enrichment of hydroxyl sanshool mixture
It is 10% that by step, (1) the fagaramide crude product of gained is diluted with water to methanol volume fraction, by D101 type macropores
Adsorbent resin column chromatography is isolated and purified, and macroporous adsorbent resin volume is 1Kg with Pericarpium Zanthoxyli fruit part by weight is dried:0.5L,
Dynamic adsorption loading, adsorption rate control after absorption is finished, first uses respectively the water and 50% second of 2.0BV in 2.0BV per hour
Alcoholic solution eluting remove impurity, then the ethanol solution eluting of 95% with 4.0BV, collect eluent, the concentrating under reduced pressure at a temperature of 50 DEG C
Obtain extractum 134g；
(3) the conversion of hydroxy-beta-sanshool
Due to step (2) gained hydroxyl sanshool mixture extractum in hydroxyl-alpha-sanshool than hydroxy-beta-Pericarpium Zanthoxyli content
Height, so needing to carry out double-bond isomerism reaction conversion, uses petroleum ether：Ethyl acetate (1:5) mixed solution dissolving hydroxyl sanshool
Mixture extractum, understands that hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 2.3 in the solution by HPLC detections:1, plus
Enter 2% iodine of the solution carries out double-bond isomerism reaction as catalyst, after 10 DEG C are reacted 36 hours, part of hydroxyl-α-sanshool
Hydroxy-beta-sanshool is changed into, hydroxyl-alpha-sanshool and hydroxy-beta-sanshool ratio are 1 in solution:2.73.
(4) the purification of hydroxy-beta-sanshool
The reacted hydroxyl sanshool mixture extractum solution of double-bond isomerism is positioned over into freezing 10h in refrigerator, is analysed
Crystalline substance, filtration drying obtains hydroxy-beta-sanshool monomer 11g that purity reaches 73.4%.
By step (4) gained hydroxy-beta-sanshool monomer petroleum ether ethyl acetate (1:2) dissolve, 8h is placed in freezing,
Crystallize, filtration drying obtains hydroxy-beta-sanshool monomer 7g, and using high phase liquid chromatograph (HPLC) hydroxyl that this example is obtained is detected
The purity of β-sanshool monomer, measures its purity for 98.2%.
Purity inspection is carried out to the finished product hydroxy-beta-sanshool monomer of following embodiments using high performance liquid chromatography (HPLC)
Survey.Wherein chromatographic condition is：Mobile phase consists of methanol-water 70:3, chromatograph column type number YMC-Pack ODS-A chromatographic columns
(4.6mm × 250mm, 5 μm)；Flow velocity 1.0mL/min；Column temperature：Room temperature；Detection wavelength 254nm.
Claims (9)
1. a kind of extraction of the preparation method of hydroxy-beta-sanshool monomer, including subject matter, enrichment, it is characterised in that：
The extraction of step one, hydroxyl sanshool mixture
Pericarpium Zanthoxyli peel crushing will be dried, Extraction solvent volume fraction is the aqueous solution of more than 85% lower alcohol to Pericarpium Zanthoxyli peel
Powder carries out merceration extraction, and liquid ratio is 1:5~1:10, extraction time is 48h, is extracted 2~3 times, merges lixiviating solution, abandons medicine
Slag, lixiviating solution concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is the 1/5~1/4 of lixiviating solution, obtains hydroxyl sanshool mixing
Thing；
The enrichment of step 2, hydroxyl sanshool mixture
The hydroxyl sanshool mixture of step one gained is diluted with water to into low-alcohol solution volume fraction 10%~20%, is passed through
Non-polar polystyrene type macroporous adsorbent resin column chromatography is isolated and purified, and is dried Pericarpium Zanthoxyli fruit weight and macroporous adsorbent resin
Volume ratio is 1Kg:0.5~1L, dynamic adsorption loading, adsorption rate is controlled in 2.0BV~3.0BV per hour, and absorption is finished
Afterwards, first respectively with the water of 2.0BV~3.0BV and 50%~60% low-alcohol solution eluting remove impurity, then with 2.5BV~4.0BV
85%~95% low-alcohol solution eluting, collect eluent, concentrating under reduced pressure obtains hydroxyl sanshool mixture extractum；
The conversion of step 3, hydroxy-beta-sanshool
Because hydroxyl-alpha-sanshool is higher than hydroxy-beta-Pericarpium Zanthoxyli content in the hydroxyl sanshool mixture extractum obtained by step 2, use
Organic solvent dissolves hydroxyl sanshool mixture extractum, adds iodine to carry out double bond cis-trans isomerization reaction as catalyst, reacts
After balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction equation is as follows：
The reaction can improve content of the hydroxy-beta-sanshool in hydroxyl sanshool mixture extractum solution；
The purification of step 4, hydroxy-beta-sanshool
Step 3 gained hydroxy-beta-sanshool mixture extractum solution is positioned over into freezing crystallize in refrigerator, filtration drying
Obtain hydroxy-beta-sanshool monomer that purity reaches more than 70%.
2. a kind of preparation method of described hydroxy-beta-sanshool monomer is required according to right 1, it is characterised in that in step one
Described low-alcohol solution is methanol, one or more mixture of ethanol.
3. a kind of preparation method of described hydroxy-beta-sanshool monomer is required according to right 1, it is characterised in that in step 2
Described non-polar polystyrene type macroporous resin model is D101, AB-8, HP20.
4. a kind of preparation method of described hydroxy-beta-sanshool monomer is required according to right 1, it is characterised in that in step 3
The organic solvent is one or more the mixture in petroleum ether, acetone, ethyl acetate.
5. the preparation method of a kind of hydroxy-beta-sanshool monomer, including one~step 3 the step of repeat claim 1：
The extraction of step one, hydroxyl sanshool mixture
Pericarpium Zanthoxyli peel crushing will be dried, Extraction solvent volume fraction is the aqueous solution of more than 85% lower alcohol to Pericarpium Zanthoxyli peel
Powder carries out merceration extraction, and liquid ratio is 1:5~1:15, extraction time is 48h, is extracted 2~3 times, merges lixiviating solution, abandons medicine
Slag, lixiviating solution concentrating under reduced pressure obtains concentrated solution, and the volume of concentrated solution is the 1/5~1/4 of lixiviating solution, obtains hydroxyl sanshool mixing
Thing；
The enrichment of step 2, hydroxyl sanshool mixture
It is 10%-20% that the hydroxyl sanshool mixture of step one gained is diluted with water to into lower alcohol volume fraction, by non-
Polarity polystyrene type macroporous adsorbent resin column chromatography is isolated and purified, and is dried Pericarpium Zanthoxyli fruit weight and macroporous adsorbent resin body
Product ratio is 1Kg:0.5~1L, dynamic adsorption loading, adsorption rate control is adsorbed after finishing in 2.0BV~3.0BV per hour,
First water respectively with 2.0BV~3.0BV and 50%~60% low-alcohol solution eluting remove impurity, then with 2.5BV~4.0BV's
85%~95% low-alcohol solution eluting, collects eluent, and concentrating under reduced pressure obtains hydroxyl sanshool mixture extractum；
The conversion of step 3, hydroxy-beta-sanshool
Hydroxyl sanshool mixture extractum obtained by step 2 is double with adding iodine to carry out as catalyst after organic solvent dissolving
Key cis-trans isomerization reacts, and after reaction balance, part of hydroxyl-α-sanshool changes into hydroxy-beta-sanshool, and reaction equation is as follows：
The reaction can improve content of the hydroxy-beta-sanshool in hydroxyl sanshool mixture extractum solution；
The purification of step 4, hydroxy-beta-sanshool
The hydroxy-beta that step 3 is obtained-sanshool mixture extractum solution is positioned over freezing crystallize in refrigerator, crosses and is filtered dry
It is dry to obtain hydroxy-beta-sanshool monomer that purity reaches more than 70%；
Step 5, recrystallization
Obtain in step 4 more than 70% hydroxy-beta-sanshool monomer organic solvent dissolving, freezing are placed, crystallize,
Filtration drying, obtains hydroxy-beta-sanshool monomer that purity reaches more than 98%.
6. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, it is characterised in that in step one
Described lower alcohol is one or more the mixture in methanol, ethanol.
7. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, it is characterised in that in step 2
Described non-polar polystyrene type macroporous resin model is D101, AB-8, HP20.
8. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, it is characterised in that：In step 3
Described organic solvent is one or more the mixture in petroleum ether, acetone, ethyl acetate.
9. the preparation method of a kind of hydroxy-beta-sanshool monomer according to claim 5, it is characterised in that：In step 5
Described organic solvent is petroleum ether, acetone, one or more mixture of ethyl acetate.
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