CN104327073B - A kind of semi-synthetic production method of vinpocetine - Google Patents

A kind of semi-synthetic production method of vinpocetine Download PDF

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CN104327073B
CN104327073B CN201410550750.6A CN201410550750A CN104327073B CN 104327073 B CN104327073 B CN 104327073B CN 201410550750 A CN201410550750 A CN 201410550750A CN 104327073 B CN104327073 B CN 104327073B
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vinpocetine
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tabersonine
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CN104327073A (en
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朱义波
邓团飞
冯正喜
陈秀秀
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GUANGZHOU PENXEN MEDICINE CO Ltd
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine

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Abstract

The invention discloses a kind of semi-synthetic production method of vinpocetine, it is that employing tabersonine hydrochloride is raw material, Pd/C is catalyst, under normal temperature and pressure, obtain tabersonine hydrogenation hydrochloride, prepare single peroxy maleic acid with hydrogen peroxide, through oxidation, reduction, transposition, sedimentation, obtain pervone by washing, then will after pervone hydrolysis, dehydration, change into vinpocetine. The semi-synthetic production method of vinpocetine of the present invention, simple to operate, safe; Without crossing column chromatography, just can obtain highly purified product; Improve yield simultaneously, reduce production costs.

Description

A kind of semi-synthetic production method of vinpocetine
Technical field
The present invention relates to technical field of organic synthesis, be specifically related to a kind of semi-synthetic production method of vinpocetine.
Background technology
Vinpocetine is a kind of natural drug obtaining from catharanthus roseus at first, belongs to indoles alkaloid, is mainly used inImprove the various symptoms that sequelae for cerebral infraction, cerebral hemorrhage sequelae, cerebral arteriosclerosis etc. are brought out. Injection vinpocetine is brainVasodilator agent, can suppress phosphodiesterase activity, increases the effect of the courier c-GMP of vascular smooth muscle relaxation, optionallyIncrease cerebral blood flow (CBF), can also suppress in addition platelet aggregation, reduce human blood viscosity, strengthen erythrocyte deformabiliy, improve bloodLiquid mobility and microcirculation, promote brain tissue ingestion of glucose, increases brain oxygen demand, improves brain metabolism.
Pervone English name vincaminc, CASNO:1617-90-9, its chemical name 14,15-dithydro-14β-hydroxy-(3 α, 16 α)-ebumamenine-14-carboxylicacidmethylester, molecular formula isC12H20N2O3, molecular weight is 354.44, structural formula is as follows:
Pervone belongs to single indole alkaloids, has very strong physiologically active; It can see through blood-brain barrier, makes diseased region brainThe oxidation Decomposition metabolism that tissue maintained and recovered glucose, makes the generation of lactic acid and the release of carbon dioxide recover normal, therebyThe little blood vessel of expansion brain, improves brain circulation; The blood flow in the normal brain activity district to normal cerebral tissue and patient's brain tissue has no significant effect,Do not affect systemic blood circulation yet; In addition also having slight sedation, is also the important of semi-synthetic cancer therapy drug vinpocetineRaw material.
The nearly family more than 30 of producer of pervone, Vinpocetine oral tablet and injection is produced in China registration; ButThat pervone, vinpocetine raw material all rely on import substantially. In the international market, the large manufacturer of pervone, vinpocetineCOVEX company of Spain and LINNEA company of Switzerland.
The preparation technology of existing production vinpocetine, one is complete synthesizing process; Another kind is semi-synthesis method, from tabersonine isThe semi-synthetic pervone of initiation material, then pervone being changed into the main process route of vinpocetine has two: wherein syntheticThe Article 1 route of pervone is after hydrogenating reduction, with metachloroperbenzoic acid or to the oxidation of nitro benzoyl hydroperoxide, thenWith triphenylphosphine reduction, the transposition of acetic acid water obtains pervone, finally changes into vinpocetine again; Article 2 route is, through catalysisHydrogenation, obtains tabersonine and adds hydrogen salt, then by single peroxy maleic acid methanol oxidation, sinks through reduction, transposition, ammonia, divides through column chromatographyFrom crystallization purifying, obtain pervone, finally change into again vinpocetine.
, in actual production, all there are problems in above-mentioned two kinds of process routes, security is poor, as all needed to adoptPressurized catalysis; The oxidant using, is all toxic articles as metachloroperbenzoic acid, to nitro benzoyl hydroperoxide, high concentration twoOxygen water, as 50%, 60%, 90%, has certain danger in the process of its storage, transport and use; Gained pervone is thickProduct, quality is low, needs, through loaded down with trivial details post processing, as multistep column chromatography and recrystallization etc., just can obtain highly purified product, and instituteThe yield obtaining is also very low, causes high expensive.
Summary of the invention
For overcoming the defect of prior art, the semi-synthetic production method that is to provide a kind of vinpocetine of the present invention, behaviourDo simple, safe; Without crossing column chromatography, just can obtain highly purified product; Improve yield simultaneously, reduce production costs.
The technical solution adopted in the present invention is as follows for achieving the above object:
A semi-synthetic production method for vinpocetine, it is that employing tabersonine hydrochloride is raw material, Pd/C is catalyst,Under normal temperature and pressure, obtain tabersonine hydrogenation hydrochloride, prepare single peroxy maleic acid with hydrogen peroxide, through oxidation, reduction, transposition, heavyFall, obtain pervone by washing, then will after pervone hydrolysis, dehydration, change into vinpocetine.
The concrete steps of the semi-synthetic production method of vinpocetine of the present invention are as follows:
1) preparation of tabersonine hydrogenation thing hydrochloride: add tabersonine hydrochloride, alcohol molten in the enamel reaction still of sealingAgent, Pd/C are catalyst, use successively nitrogen, hydrogen exchange, then logical hydrogen rapid stirring under normal temperature and pressure, and in reaction, fromThief hole sampling, with TLC analysis, until without raw material tabersonine hydrochloride, after reaction finishes, filter, reclaim Pd/C, obtains its ripplePeaceful hydrogenation thing hydrochloride;
2) preparation of single peroxy maleic acid: in enamel reaction still, add hydrogen peroxide, rapid stirring, open refrigeration system,Cool to-10 DEG C～0 DEG C, add maleic anhydride, add temperature to remain on-10 DEG C～0 DEG C, finish ,-5 DEG C～-0 DEG C temperatureLower continuation reaction 4 hours, adds solvent dilution, and rapid stirring, has reacted rear refrigeration;
3) oxidation reaction: to containing in steps 1) the reactor of tabersonine hydrogenation thing hydrochloride in add solvent, startup is stirredMix, open refrigeration system and drop to-25 DEG C～-15 DEG C, under nitrogen protection, drip step 2) single peroxy maleic acid of preparing is moltenLiquid, in dropping process, temperature remains on-25 DEG C～-10 DEG C, after dripping, with TLC analysis, until without raw material tabersonine hydrogenation thingHydrochloride;
4) reduction reaction, translocation reaction and ammonia are heavy: in step 3) reactor in slowly add reductive acid, and in this temperatureUnder degree, rapid stirring 20-40 minute, rises to room temperature, stirs 1-3h, with TLC analysis, the spot size at product pervone and assorted peakWhen constant rate, translocation reaction finishes, and is cooled to 10～15 DEG C, is slowly added dropwise to 5% pH adjusting agent, and adjusting its pH is 8.5-9.5, be then cooled to 0 DEG C, stirring and crystallizing 1-3 hour, filters, and washs successively with first alcohol and water, drains, and is dried, and obtains pervone;
5) Changchun amino acid is prepared in pervone basic hydrolysis: above-mentioned pervone is dissolved with ethanol, slowly add NaOH, byGradually increase the temperature to 60～70 DEG C, stirring reaction 2h, TLC detects to reactant reaction complete, is placed to after room temperature reactantPour in frozen water, regulate the pH to 7 of mixture under stirring with hydrochloric acid, filter, washing, is dried and obtains sour intermediate I;
6) preparation of vinpocetine: slowly in intermediate I, add POCl3, in 60～70 DEG C of stirring reactions, TLC inspectionSurvey to reactant reaction completely, obtain acyl chlorides intermediate II;
In 25～10 DEG C with temperature under, to the caustic alcohol that adds equivalent in acyl chlorides intermediate II, stirring reaction, TLCDetect to reactant reaction completely, filter washing, obtain vinpocetine with methylene chloride-methanol crystallization after dry.
The synthetic route of the semi-synthetic production method of vinpocetine of the present invention is as follows:
In said method, step 1) in the quality of the tabersonine hydrochloride that adds be alcoholic solvent 8%-10%, Pd/C'sQuality is 10%～15% of tabersonine hydrochloride.
In said method, step 1) described in alcoholic solvent be in methyl alcohol, 80%～95% ethanol, absolute ethyl alcohol or isopropyl alcoholOne.
In said method, step 2) in solvent be the one in methyl alcohol, ethanol or isopropyl alcohol.
In the present invention, hydrogen peroxide concentration is too high can be transported in impact, increases danger, in the time of oxidation, produces too much oxygenChange impurity; And the yield of the too low product of hydrogen peroxide reduces. Preferably, in said method, rapid 2) in, the mass concentration of hydrogen peroxide is25%～35%, the mol ratio of hydrogen peroxide and tabersonine hydrogenation thing hydrochloride is (1.0-1.4): 1, the amount of maleic anhydride with addHydrogen peroxide mol ratio is (5.1～6): 1.
In said method, step 3) in, described alcoholic solvent is methyl alcohol or absolute ethyl alcohol, its addition is tabersonine hydrochloride10 times of quality.
In said method, step 4) in, described reductive acid is sodium pyrosulfite or sodium sulfite, itself and step 2) inHydrogen peroxide mol ratio be (0.4～1): 1; Described pH adjusting agent is the one in ammoniacal liquor, triethylamine or sodium carbonate.
In said method, step 5) in, in pervone, add 1.2 Equivalent Hydrogen sodium oxide molybdenas.
In said method, step 6) in, in intermediate I, add the POCl3 of 1.1 equivalents, in acyl chlorides intermediate II, addThe caustic alcohol of equivalent.
Compared to existing technology, beneficial effect of the present invention is:
1. the semi-synthetic production method of vinpocetine of the present invention adopts simple production technology, divides without column chromatographyJust can produce highly purified product from waiting, more than purity to 99.0%;
2. the semi-synthetic production method process route of vinpocetine of the present invention is simple, and yield reaches 56%～70%, production cost and existing technique ratio, reduce greatly, can create significant economic worth;
3. the semi-synthetic production method catalytic hydrogenation of vinpocetine of the present invention adopts normal temperature and pressure reaction, increasesAdd security.
4. the tabersonine hydrochloride that the semi-synthetic production method of vinpocetine of the present invention adopts, its purity >=90%, just can obtain qualified product pervone, provide guarantee for realizing low cost;
5. the semi-synthetic production method of vinpocetine of the present invention adopts the hydrogen peroxide of low concentration (25～35%), forObtain high-purity pervone product, simplify purifying process, guarantee is provided; In addition, also in the process that stores, transports and useReduce greatly danger coefficient;
6. the pervone of the semi-synthetic production method of vinpocetine of the present invention in the process of preparing vinpocetineAfter can also being further purified for the preparation of pharmaceutical grade pervone.
Below in conjunction with concrete embodiment, the present invention is described in further detail.
Brief description of the drawings
Fig. 1 is pervone nucleus magnetic hydrogen spectrum figure of the present invention;
Fig. 2 is pervone liquid chromatogram of the present invention;
Fig. 3 is vinpocetine nucleus magnetic hydrogen spectrum figure of the present invention;
Fig. 4 is vinpocetine liquid chromatogram of the present invention.
Detailed description of the invention
In following examples, relate to the account form of pervone yield as follows:
Wherein, W (yield) represents the total recovery of pervone, M1Represent the quality of raw material tabersonine hydrochloride, w1Represent raw materialThe purity of tabersonine hydrochloride, the existing purity adopting is: 91%～97%, M2Represent the quality of qualified pervone.
The account form of yield that relates to vinpocetine in following examples is as follows:
Wherein, W ' (yield) represents vinpocetine total recovery, M3Represent the quality of raw material pervone, M4Represent qualified lengthThe quality of Chun Xiting.
Embodiment 1
A semi-synthetic production method for vinpocetine, concrete steps are as follows:
1) preparation of tabersonine hydrogenation thing hydrochloride:
In a 100L enamel reaction still, add 90% ethanol of 41kg, open after stirring, then add 5kg(13.41mol) tabersonine hydrochloride (purity: 91.15%), add fast 10% the new Pd/C of 0.5kg, good seal kettle cover,With nitrogen replacement three times, then use hydrogen (purity: 99.999%) after displacement three times, logical hydrogen under normal temperature and pressure, rapid stirring,React after 10 hours, from thief hole sampling, with TLC point plate analysis, until without raw material tabersonine hydrochloride, after reaction finishes, mistakeFilter, reclaim Pd/C, and with ethanol 0.5kg washing leaching cake, collection good seal Pd/C, weight in wet base 0.80kg, by mother liquor in 60 DEG C ,-Under 0.09～-0.098MPa, decompression distillation, collects cut second alcohol and water, obtains solid tabersonine hydrogenation hydrochloride 4.87kg;
2) preparation of single peroxy maleic acid:
In a 50L enamel reaction still, add 30% hydrogen peroxide 1.52kg (13.41mol), rapid stirring, opensRefrigeration system, cools to-10 DEG C～0 DEG C, slowly adds maleic anhydride 7.23kg, adds temperature to remain on-10 DEG C～0 DEG C, addsFinish, continue reaction 4 hours at-5 DEG C～-0 DEG C temperature, add methyl alcohol 30kg dilution, rapid stirring 1 hour is protected at 0 DEG CHold, stand-by;
3) oxidation reaction:
In 200L glass reaction still, add absolute methanol 40kg, open and stir, by gained solid tabersonine hydrogenation hydrochloric acidSalt 4.87kg also adds in reactor, opens refrigeration system and cools to-20 DEG C, by molten prepared second step single peroxy maleic acidLiquid is transferred in gravity tank, under nitrogen protection, drips single peroxy maleic acid solution, in dropping process temperature remain on-20 DEG C～-10 DEG C, after dripping, with TLC analysis, until without raw material tabersonine hydrogenation thing hydrochloride, 2 hours reaction time;
4) reduction reaction, translocation reaction and sedimentation:
By the sodium pyrosulfite of 1.25kg, at-15 DEG C～-10 DEG C, slowly add, temperature is controlled at-15 DEG C～-10DEG C, throw and finish, under this temperature, rapid stirring 30 minutes, rises to room temperature, stirs 2h, with TLC analysis, the spot at product pervone and assorted peakWhen point size does not change, translocation reaction finishes; Be cooled to 10～15 DEG C, slowly splash into 5% the about 40kg of ammoniacal liquor, adjust itPH:8.8, is then cooled to 0 DEG C, and stirring and crystallizing 2 hours is filtered, and with methyl alcohol and water washing filter cake, drains, and at 50 DEG C, decompression is dryDry, obtain pervone 2.86kg, total recovery is 66.1%, analyzes through HPLC, area normalization content is 99.13%;
5) pervone macromolecule alkali for hydrolysis obtains Changchun amino acid;
Pervone is dissolved with ethanol, slowly adds the NaOH of 1.2 equivalents, increase the temperature to gradually 60～70 DEG C,Stirring reaction 2h, TLC detects to reactant reaction complete, reactant is poured in frozen water after being placed to room temperature, stirs lower using10% hydrochloric acid regulates the pH to 7 of mixture, filters, and washing, 60 DEG C dry obtains sour intermediate I:
6) prepare vinpocetine:
Slowly, to the POCl3 that adds 1.1 equivalents in intermediate I, in 60～70 DEG C of stirring reactions, TLC detects to reactionThing reacts completely, and obtains acyl chlorides intermediate II; In 25～10 DEG C with temperature under, to adding equivalent in acyl chlorides intermediate IICaustic alcohol, stirring reaction, TLC detects to reactant reaction complete, filters washing, after being dried, obtains with methylene chloride-methanol crystallizationTo vinpocetine, calculate taking pervone as raw material, the yield of vinpocetine is: 94%.
Embodiment 2:
A semi-synthetic production method for vinpocetine, concrete steps are as follows:
1) preparation of tabersonine hydrogenation thing hydrochloride:
In a 100L enamel reaction still, add the technique ethanol of 41kg (50L), open and stir, add 5kg(13.41mol) tabersonine hydrochloride (purity 98%), adds fast 10% the new Pd/C of 0.4kg, then adds in embodiment 1Weight in wet base 0.8kg collects the recovery Pd/C of good seal, good seal kettle cover, with nitrogen replacement three times, then use hydrogen (purity:99.999%) replace after three times, logical hydrogen is under normal temperature and pressure, and rapid stirring, reacted after 10 hours, from thief hole sampling, usesTLC analyzes, and reacts completely to tabersonine hydrochloride; After reaction finishes, filter, reclaim Pd/C, and wash and filter with ethanol 0.5kgCake, collects good seal Pd/C, weight in wet base 0.80kg, by mother liquor in 60 DEG C, under-0.09～-0.098MPa, decompression distillation, collection is heated up in a steamerDivide second alcohol and water, obtain solid tabersonine hydrogenation hydrochloride 4.90kg;
2) preparation of single peroxy maleic acid
In a 50L enamel reaction still, add 27% hydrogen peroxide 1.67kg (14.75mol), stir with 100r/minMix, open refrigeration system, cool to-10 DEG C～0 DEG C, slowly add maleic anhydride 7.9kg, add temperature to remain on-10 DEG C～0DEG C, finish, at-5 DEG C～-0 DEG C temperature, continue reaction 4 hours, add methyl alcohol 40kg dilution, rapid stirring 1 hour, in 0 DEG CLower preservation, stand-by;
3) oxidation reaction
In 200L glass reaction still, add absolute methanol 40kg, open and stir, by gained solid tabersonine hydrogenation hydrochloric acidSalt 4.9kg also adds in reactor, opens refrigeration system and cools to-19 DEG C, by molten prepared second step single peroxy maleic acidLiquid is transferred in gravity tank, under nitrogen protection, drips single peroxy maleic acid solution, and in dropping process, temperature remains on-15 DEG C～0DEG C, after dripping, with TLC analysis, until without about 2 hours of raw material tabersonine hydrogenation thing hydrochloride reaction time;
4) reduction reaction, translocation reaction and sedimentation
By the sodium sulfite of 1.37kg, at-15 DEG C～-10 DEG C, slowly add, temperature is controlled at-15 DEG C～-10 DEG C,Throw and finish, at this temperature, rapid stirring 30 minutes, rises to room temperature, stirs 2h, with TLC analysis, the spot at product pervone and assorted peakWhen point size does not change, translocation reaction finishes; Be cooled to 10～15 DEG C, slowly splash into 5% the about 40kg of Na2CO3, adjust itPH:9, is then cooled to 0 DEG C, and stirring and crystallizing 2 hours is filtered, with methyl alcohol and water washing filter cake, drain, and drying under reduced pressure at 50 DEG C,Obtain pervone 2.9kg, total recovery is 62.9%, analyzes through HPLC, and area normalization content is 99.39%;
5) pervone macromolecule alkali for hydrolysis obtains Changchun amino acid;
Vincamine is dissolved with ethanol, slowly add the NaOH of 1.2 equivalents, increase the temperature to gradually 60～70DEG C, stirring reaction 2h, TLC detects to reactant reaction complete, reactant is poured in frozen water after being placed to room temperature, stirs lower using10% hydrochloric acid regulates the pH to 7 of mixture, filters, and washing, 60 DEG C dry obtains sour intermediate I:
6) prepare vinpocetine:
Slowly, to the POCl3 that adds 1.1 equivalents in intermediate I, in 60～70 DEG C of stirring reactions, TLC detects to reactionThing reacts completely, and obtains acyl chlorides intermediate II; In 25～10 DEG C with temperature under, to adding equivalent in acyl chlorides intermediate IICaustic alcohol, stirring reaction, TLC detects to reactant reaction complete, filters washing, after being dried, obtains with methylene chloride-methanol crystallizationTo vinpocetine,, calculate taking pervone as raw material, the yield of vinpocetine is: 94%.
Referring to Fig. 1, Fig. 2, in embodiment 1 and embodiment 2, gained pervone characterization parameter and performance are as follows:
1H-NMR(CDCl3,400MHz):δ(ppm)＝7.48(t,1H),7.26(s,1H),7.12(t,1H),4.65(s,3H),2.15-3.34(m,2H),1.3(t,3H)。
Gained pervone is white or flaxen crystalline powder, water insoluble, is slightly soluble in alcohols, is dissolved in chloroform or twoChloromethanes. Fusing point: 229 DEG C～231 DEG C.
Molecular formula: C21H26N2O3
Molecular weight: 354.44.
As follows referring to Fig. 3, Fig. 4 vinpocetine characterization parameter and performance:
Gained vinpocetine is: almost white crystals or powder, and odorless, tasteless. Easily molten in glacial acetic acid, be dissolved in chloroform or96% ethanol is slightly molten in dimethyl formamide or acetone, and slightly soluble in methyl alcohol or ethanol is almost insoluble in water; Fusing point this productFusing point be D20+114 ° of 149-152 DEG C of (decomposition) [α] (C=1, pyridine);
Molecular formula: C22H26N2O2
Molecular weight: 350.46.
Above-mentioned embodiment is only the preferred embodiment of the present invention, can not limit the scope of protection of the invention with this,The variation of any unsubstantiality that those skilled in the art does on basis of the present invention and replacement all belong to institute of the present inventionClaimed scope.

Claims (9)

1. a semi-synthetic production method for vinpocetine, is characterized in that, comprises the steps:
1) preparation of tabersonine hydrogenation thing hydrochloride: in the enamel reaction still of sealing, add tabersonine hydrochloride, alcoholic solvent,Pd/C is catalyst, uses successively nitrogen, hydrogen exchange, and then logical hydrogen rapid stirring under normal temperature and pressure, in reaction, from samplingHole sampling, with TLC analysis, until without raw material tabersonine hydrochloride, after reaction finishes, filter, reclaim Pd/C, obtains tabersonine and addsHydrogen thing hydrochloride;
2) preparation of single peroxy maleic acid: in enamel reaction still, add hydrogen peroxide, rapid stirring, open refrigeration system, coolingTo-10 DEG C～0 DEG C, add maleic anhydride, add temperature to remain on-10 DEG C～0 DEG C, finish, at-5 DEG C～0 DEG C temperature, continueReact 4 hours, add solvent dilution, rapid stirring, has reacted rear refrigeration;
3) oxidation reaction: to containing in steps 1) the reactor of tabersonine hydrogenation thing hydrochloride in add solvent, start and stir, openOpen refrigeration system and drop to-25 DEG C～-15 DEG C, under nitrogen protection, drip step 2) single peroxy maleic acid solution of preparing, dripIn process, temperature remains on-25 DEG C～-10 DEG C, after dripping, with TLC analysis, until without raw material tabersonine hydrogenation thing hydrochloride;
4) reduction reaction, translocation reaction and ammonia are heavy: in step 3) reactor in slowly add reductive acid, and in this temperatureUnder, rapid stirring 20-40 minute, rises to room temperature, stirs 1-3h, with TLC analysis, the spot size ratio at product pervone and assorted peakWhen example does not change, translocation reaction finishes, and is cooled to 10～15 DEG C, is slowly added dropwise to 5% pH adjusting agent, and adjusting its pH is 8.5-9.5, be then cooled to 0 DEG C, stirring and crystallizing 1-3 hour, filters, and washs successively with first alcohol and water, drains, and is dried, and obtains pervone;
5) Changchun amino acid is prepared in pervone basic hydrolysis: above-mentioned pervone is dissolved with ethanol, slowly add NaOH, rise graduallyHigh-temperature to 60～70 DEG C, stirring reaction 2h, TLC detects to reactant reaction complete, reactant is poured into after being placed to room temperatureIn frozen water, regulate the pH to 7 of mixture under stirring with hydrochloric acid, filter, washing, is dried and obtains sour intermediate I;
6) preparation of vinpocetine: slowly add POCl3 in intermediate I, in 60～70 DEG C of stirring reactions, TLC detects extremelyReactant reaction is complete, obtains acyl chlorides intermediate II;
In 25～10 DEG C with temperature under, to the caustic alcohol that adds equivalent in acyl chlorides intermediate II, stirring reaction, TLC detectsComplete to reactant reaction, filter washing, after being dried, obtain vinpocetine with methylene chloride-methanol crystallization.
2. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 1) in add itThe quality of the peaceful hydrochloride of ripple is the 8%-10% of alcoholic solvent, and the quality of Pd/C is 10%～15% of tabersonine hydrochloride.
3. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 1) described in alcohol moltenAgent is the one in methyl alcohol, 80%～95% ethanol, absolute ethyl alcohol or isopropyl alcohol.
4. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 2) in solvent beOne in methyl alcohol, ethanol or isopropyl alcohol.
5. the matter of hydrogen peroxide the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that, rapid 2)Amount concentration is 25%～35%, and the mol ratio of hydrogen peroxide and tabersonine hydrogenation thing hydrochloride is (1.0-1.4): 1, maleic anhydrideAmount is (5.1～6) with adding hydrogen peroxide mol ratio: 1.
6. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 3) in, described alcoholSolvent is methyl alcohol or absolute ethyl alcohol, and its addition is 10 times of tabersonine hydrochloride quality.
7. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 4) in, describedReductive acid is sodium pyrosulfite or sodium sulfite, itself and step 2) in hydrogen peroxide mol ratio be (0.4～1): 1; Described pHConditioning agent is the one in ammoniacal liquor, triethylamine or sodium carbonate.
8. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 5) in, pervoneIn add 1.2 Equivalent Hydrogen sodium oxide molybdenas.
9. the semi-synthetic production method of vinpocetine according to claim 1, is characterized in that step 6) in, intermediate IIn add the POCl3 of 1.1 equivalents, in acyl chlorides intermediate II, add the caustic alcohol of equivalent.
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