CN103554309B - A kind of resin for tabersonine separation and purification and application thereof - Google Patents
A kind of resin for tabersonine separation and purification and application thereof Download PDFInfo
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- CN103554309B CN103554309B CN201310544809.6A CN201310544809A CN103554309B CN 103554309 B CN103554309 B CN 103554309B CN 201310544809 A CN201310544809 A CN 201310544809A CN 103554309 B CN103554309 B CN 103554309B
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Abstract
A kind of resin for tabersonine separation and purification and application thereof.Be initial resin with commercial resin, after chloromethylation, be obtained by reacting new type resin with amino acid; It is extremely low that this new type resin extracts the adsorptive power of tabersonine in acid solution to Voacanga seed, but can impurity optionally in adsorbing and extracting acid solution; When new type resin being used for tabersonine separation and purification, first by Voacanga Seeds preprocess, pulverizing, with organic solvent heating and refluxing extraction, acidifying, acid solution is after new type resin purifying, target product tabersonine to be enriched in more than upper prop in liquid and water lotion, collect liquid through alkalization, extraction, concentrated after product tabersonine.This new type resin is used for the separation and purification of tabersonine, improve the rate of recovery of tabersonine, and upper prop purge process is without the need to the alcohol wash of high density, reduces production cost and solvent load.
Description
Technical field
The present invention relates to natural product extraction separation technology field, be specifically related to a kind of resin and application thereof of separation and purification.
Background technology
Tabersonine, also known as willow leaf tabersonine (Tabersonine, CASNO.44289-63-4), be a kind of important biomolecule alkali in African Voacanga, molecular formula is C
21h
24n
2o
2, relative molecular mass is 336.42, and its chemical name is Aspidospermidine-3-carboxylicacid, 2,3,6,7-tetradehydro-(5 α, 12 β, 19 α)-methylseter.Research shows, tabersonine has hypotensive effect, is at present for the synthesis of the main raw material of cancer therapy drug vinpocetin.
The extraction and separation method of tabersonine is reported in patent US3758478, adopt organic solvent extraction, repeatedly acid rinsing, alkalization, organic solvent extraction, the steps such as recrystallization carry out separation and purification tabersonine, and the method operating process is complicated, tabersonine yield is low, be unfavorable for suitability for industrialized production, and adopt the noxious solvent such as benzene and chloroform, have larger injury to producers.
The patent of invention that publication number is CN101250188A, name is called a kind of preparation technology of willow leaf tabersonine, wherein describe with macroporous resin separation and purification tabersonine, the method is practical in actual production, but the commercial resins such as D101, XDA-6, XDA-7 that this patented method adopts lack the adsorption selectivity to tabersonine and sour extract impurity, result in that resin demand is large, the tabersonine rate of recovery reduces, large, the used extraction solvent of solvent load is as normal hexane, the problems such as costliness, increase production cost.
Summary of the invention
Technical problem to be solved by this invention is to provide the new type resin for high efficiency separation purifying tabersonine of a kind of low cost, highly selective, and the method for separation and purification tabersonine is carried out with this resin, the method resin demand is few, the tabersonine rate of recovery is high, solvent load is few, effectively can reduce production cost.
In order to solve the problems of the technologies described above, the present invention take commercial resin as initial resin, by initial resin first through chloromethylation, is then obtained by reacting new type resin with amino acid.Research shows, the absorption Voacanga seed of this resinoid energy efficient selective extracts the impurity in acid solution, and the tabersonine in acid solution to be directly collected in more than upper prop in liquid and water lotion.Tabersonine is collected basified after through the extraction of the low toxicity low cost solvent such as ethyl acetate, highly purified tabersonine can be obtained.
The concrete making step of this new type resin is as follows:
(1) commercial resin after pretreatment, be fully swelling in the dichloromethane solution of resin quality 5 ~ 10 times at volume, add sodium-chlor that quality is resin quality 0.5 ~ 2 times, zinc chloride that quality is resin quality 0.5 ~ 2 times, volume are return stirring 10 ~ 40 hours after the chloromethyl methyl ether of resin quality 0.3 ~ 1 times, filtration, washing, drying, obtain chloromethyl resin; The preferred D101 of commercial resin;
(2) by the chloromethyl resin obtained in step (1) in volume be resin quality 1 ~ 10 times alcoholic solution in fully swelling, add amino acid that quality is resin quality 0.5 ~ 4 times, water that pyridine that quality is resin quality 0.5 ~ 4 times and volume are resin quality 10 ~ 40 times, return stirring 8 ~ 30 hours, filter, washing, dry amino acid modified new type resin; Amino acid can be any one in L-Ala, α-amino-isovaleric acid, leucine, Isoleucine, proline(Pro), phenylalanine, tryptophane, methionine(Met), glycine, Serine, Threonine, halfcystine, tyrosine, l-asparagine, glutamine, Methionin, arginine, Histidine, aspartic acid, L-glutamic acid; Alcoholic solution particular methanol solution.
This new type resin is as follows for separating of the step of tabersonine in purifying Voacanga seed:
A. Voacanga Seeds preprocess, pulverizes;
B. organic solvent heating and refluxing extraction, acidifying: repeatedly extract with organic solvent, united extraction liquid, decompression removing organic solvent, adds sour water acidifying in concentrated solution; Organic solvent preferably 90% methyl alcohol;
C. acid solution is through new type resin purifying: new type resin in acid solution, liquid and water lotion more than collection upper prop;
D. more than upper prop, liquid and water lotion are 9 ~ 11 through alkalization pH, with organic solvent extraction, concentrate, obtain product tabersonine; Extracting solvent used is one in sherwood oil, ethyl acetate, methylene dichloride, trichloromethane, benzene, toluene.
Compared with existing patent, the features and advantages of the invention are: adopt the new type resin of highly selective to extract acid solution to Voacanga seed and carry out separation and purification, introduce in commercial resin after amino acid functional group becomes new type resin and by the 246mg/g before introducing, 6mg/g is reduced to the adsorptive capacity extracting tabersonine in acid solution, and new type resin still remains the high absorption capacity to impurity component in acid solution, extract acid solution after new type resin selective adsorption, target product tabersonine is directly collected in more than upper prop in liquid and water lotion, and the impurity absorption in acid solution is on new type resin.The high-selectivity adsorption of new type resin effectively reduces resin demand, process 1Kg Voacanga seed, and the new type resin dry weight of needs is about 140g; The adsorptive power that new type resin is extremely weak to tabersonine, improve the rate of recovery of tabersonine and decrease solvent load, the rate of recovery is greater than 90%.Because impurity obtains effective separation with tabersonine after new type resin purifying, the alkalization extraction process of aftertreatment as extraction solvent, can adopt the sherwood oil of economic low toxicity, ethyl acetate equal solvent as extraction solvent without the need to the normal hexane of costliness.
Embodiment
The part new type resin related in the present invention and the method for separating of purifying tabersonine thereof, illustrate, but protection scope of the present invention is not limited to this with the following example.
Embodiment 1:
(1) 150gD101 dried resin good for pre-treatment is added in three-necked bottle, add 1000ml methylene dichloride to soak swelling 24 hours, add 200g sodium-chlor, 150g zinc chloride, 700ml chloromethyl methyl ether respectively afterwards, return stirring 15 hours under 50 DEG C of conditions, by deionized water, methanol wash, drying, obtains chloromethyl resin;
(2) take 100g chloromethyl resin to add in three-necked bottle, then add swelling 12 hours of 350ml methyl alcohol immersion.72g glycine, 75g pyridine are added in the 2000ml aqueous solution, and then adds in three-necked bottle, 90 DEG C of return stirrings 24 hours, filter, washing, dry, obtain the new type resin that glycine is modified;
(3) taking 100g Voacanga seed to pulverize, is the methanol solution 400ml refluxing extraction five times of 90% with mass ratio, united extraction liquid, concentratedly removes alcoholic solution; Add the hydrochloric acid soln acidifying that 250ml mass ratio is 1% again, filter, obtain Voacanga seed and extract acid solution;
(4) the dry new type resin modified by 20g glycine in step (2) is with water-soluble swollen; The direct loading of acid solution that step (3) is obtained, liquid and water lotion more than collection upper prop;
(5) more than upper prop step (4) obtained, liquid and water lotion ammoniacal liquor regulate pH to 9, use 150ml extraction into ethyl acetate, the concentrated tabersonine 1.71g obtaining purity and be greater than 98%.
Embodiment 2:
(1) 150gD101 dried resin good for pre-treatment is added in three-necked bottle, add 800ml methylene dichloride to soak swelling 24 hours, then 150g sodium-chlor, 170g zinc chloride, 400ml chloromethyl methyl ether is added respectively, return stirring 20 hours under 50 DEG C of conditions, by deionized water, methanol wash, drying, obtains chloromethyl resin;
(2) taking 100g chloromethyl resin adds in three-necked bottle, adds 350ml methyl alcohol and soaks swelling 12 hours.Take 110g α-amino-isovaleric acid, 70g pyridine adds in the 1700ml aqueous solution, and then add in three-necked bottle, 90 DEG C of return stirrings 20 hours, filter, washing, dry, obtain the new type resin that α-amino-isovaleric acid is modified;
(3) taking 100g Voacanga seed to pulverize, is the methanol solution 400ml refluxing extraction five times of 90% with mass ratio, united extraction liquid, concentrated removal alcoholic solution, add the sulphuric acid soln acidifying that 250ml mass ratio is 3%, filter, obtain Voacanga seed and extract acid solution;
(4) the dry new type resin modified by 15g α-amino-isovaleric acid in step (2) is with water-soluble swollen; The direct loading of acid solution that step (3) is obtained, liquid and water lotion more than collection upper prop;
(5) more than upper prop step (4) obtained, liquid and water lotion ammoniacal liquor regulate pH to 10, use 150ml dichloromethane extraction, the concentrated tabersonine 1.65g obtaining purity and be greater than 98%.
Claims (7)
1. for a resin for tabersonine purifies and separates, it is characterized in that: comprise the steps:
(1) commercial resin after pretreatment, be swelling in the dichloromethane solution of resin quality 5 ~ 10 times at volume, add sodium-chlor that quality is resin quality 0.5 ~ 2 times, zinc chloride that quality is resin quality 0.5 ~ 2 times, volume be after the chloromethyl methyl ether of resin quality 0.3 ~ 1 times, return stirring 10 ~ 40 hours, filtration, washing, drying, obtain chloromethyl resin;
(2) by the chloromethyl resin obtained in step (1) in volume be resin quality 1 ~ 10 times alcoholic solution in swelling, add amino acid that quality is resin quality 0.5 ~ 4 times, water that pyridine that quality is resin quality 0.5 ~ 4 times and volume are resin quality 10 ~ 40 times, return stirring 8 ~ 30 hours, filter, washing, dry amino acid modified resin.
2. resin according to claim 1, is characterized in that: described commercial resin is D101.
3. resin according to claim 1, is characterized in that: described amino acid is the one in L-Ala, α-amino-isovaleric acid, leucine, Isoleucine, proline(Pro), phenylalanine, tryptophane, methionine(Met), glycine, Serine, Threonine, halfcystine, tyrosine, l-asparagine, glutamine, Methionin, arginine, Histidine, aspartic acid, L-glutamic acid.
4., by a method for resin separation purification tabersonine according to claim 1, it is characterized in that: comprise the steps:
A. Voacanga Seeds preprocess, pulverizes;
B. organic solvent heating and refluxing extraction, acidifying;
C. acid solution is through amino acid modified resin purification;
D. more than upper prop, liquid and water lotion alkalize, extract, concentrate, and obtain product tabersonine.
5. method according to claim 4, is characterized in that: described amino acid modified resin is for separating of the upper prop purification phase in purge process.
6. method according to claim 4, is characterized in that: acid solution is after amino acid modified resin purification, and tabersonine to be enriched in more than upper prop in liquid and water lotion.
7. method according to claim 4, is characterized in that: described extraction solvent used is the one in sherwood oil, ethyl acetate, methylene dichloride, trichloromethane, benzene, toluene.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310544809.6A CN103554309B (en) | 2013-11-07 | 2013-11-07 | A kind of resin for tabersonine separation and purification and application thereof |
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| CN201310544809.6A CN103554309B (en) | 2013-11-07 | 2013-11-07 | A kind of resin for tabersonine separation and purification and application thereof |
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| CN103554309A CN103554309A (en) | 2014-02-05 |
| CN103554309B true CN103554309B (en) | 2016-03-30 |
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| CN108484603B (en) * | 2018-04-02 | 2020-06-09 | 太阳树（厦门）生物工程有限公司 | Method for extracting tabersonine from African voacanga |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250188A (en) * | 2008-03-25 | 2008-08-27 | 西安皓天生物工程技术有限责任公司 | Technique for preparing willow leaf tabersonine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250188A (en) * | 2008-03-25 | 2008-08-27 | 西安皓天生物工程技术有限责任公司 | Technique for preparing willow leaf tabersonine |
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