CN1687064A - Synthetic method for preparing fibrauretine of antibiosis anti-inflammatory drug - Google Patents
Synthetic method for preparing fibrauretine of antibiosis anti-inflammatory drug Download PDFInfo
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- CN1687064A CN1687064A CN 200510064486 CN200510064486A CN1687064A CN 1687064 A CN1687064 A CN 1687064A CN 200510064486 CN200510064486 CN 200510064486 CN 200510064486 A CN200510064486 A CN 200510064486A CN 1687064 A CN1687064 A CN 1687064A
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- fibrauretine
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- inflammatory drug
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Abstract
The present invention relates to a nwe synthesis method for preparing palmatine. Said invention is characterized by utilizing known compound and adopting a certain chemical reaction to artificially synthesize palmatine, its operation is easy and its cost is low.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, specifically, relate to a kind of synthesis preparation method of fibrauretine of antibiosis anti-inflammatory drug.
Background technology
Herba fibraureae recisae has another name called Root or stem of Wintergreen Barberry, and huangteng is root and the stem of menispermaceous plants herba fibraureae recisae.Cold in nature, it is sweet, bitter, poisonous to distinguish the flavor of, and goes into the heart, liver two warps." herba fibraureae recisae gives birth to the south of the Five Ridges in the Compendium of Material Medica record.If shape is the root of fangji, this rattan of natives' informal dress, and the drinking bout food is poisonous, does not also send out naturally." " Luchuan book on Chinese herbal medicine " cloud: " detoxifcation of purging heat, defaecation, the poison that anhydrates, detumescence.Control hot strongly fragrant constipation, dysentery, Shi Shui, sore carbuncle, pemphigus, cute conjunctivitis." " Guangxi herbal medicine " title " clearing away the heart-fire, diuresis.Control dysentery, acute gastroenteritis, acute tonsillitis, pharyngolaryngitis, conjunctivitis, pulmonary tuberculosis, sore furuncle, burn; Can prevent epidemic meningitis." modern " Chinese medicine voluminous dictionary " claim its " heat-clearing, detoxifcation, diuresis, defaecation.Control food poisoning, hot strongly fragrant constipation, dysentery, infectious hepatitis, sore carbuncle, cute conjunctivitis, swelling and pain in the throat." ancient Chinese medicine doctor gets the merit of its detoxifcation of purging heat, and is used for the treatment of sore, carbuncle and painful swelling, the gastrointestinal system inflammation all obtains curative effect preferably.
Fibrauretin is a kind of alkaloid (Palmatine) that extracts from herba fibraureae recisae, has effects such as clearing heat and detoxicating, that anti-inflammatory is antibacterial.Be widely used in gynecological inflammation, bacillary dysentery, enteritis, respiratory tract and urinary tract infection, surgical infection, eye conjunctivitis etc.Because determined curative effect was just recorded by Chinese Pharmacopoeia early than 1977.With the Fibrauretin is that the preparation that raw material is made has Fibrauretin sheet, Fibrauretin injection liquid etc., from listing so far, through a large amount of clinical applications, has obtained better therapeutic effect.At present, the Fibrauretin preparation is used comparatively extensive clinically, but its output does not far reach the market requirement, major cause is that crude drug herba fibraureae recisae growth cycle is longer, in adopting the valve process for a long time, has faced exhausted stage, to from natural herba fibraureae recisae, extract Fibrauretin, become increasingly difficult.So the preparation method of the synthetic Fibrauretin of research replaces natural Fibrauretin, alleviates the herb resource of atrophy day by day, is current terms of settlement preferably.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of synthetic Fibrauretin raw material.
The present invention realizes by following technical scheme:
1, the preparation of veratrole (methylation reaction)
The methyl catechol veratrole
Operation: methyl catechol, methyl-sulfate are dropped in the retort, stir down, at 45～50 ℃ of dropwise liquids.Control 45～50 ℃ of insulations 1 hour.Temperature rising reflux 1 hour, reaction finishes.Be cooled to 40 ℃ and add water, stir, discharging is washed to neutrality, and the heating decompression dehydration gets veratrole, and is standby.
2,3, the preparation of 4-dimethoxybenzeneacetonitrile (chloromethylation, cyanogenation)
Veratrole 3,4-dimethoxy acetonitrile
Operation: hydrochloric acid, Paraformaldehyde 96 are dropped in the retort, about 1 hour of stirring at room after the dissolving, is chilled to below 25 ℃, add veratrole, chloroform, be controlled at about 30 ℃ of reactions 5 hours (dripping trichlorine oxygen first phosphorus after 2 hours in reaction), reaction finishes, discharging, be washed to PH3～4, add 30% anhydrous sodium sulfate dehydration, reclaim chloroform, it is standby to get muriate.
Sodium cyanide, water, TBEA and sodium hydroxide are dropped in the retort, stirring and dissolving, muriate is dropped in the dissolving back, 35～40 ℃ of insulation reaction 2 hours, blowing was washed to no sodium cyanide, add 1/4 volume of ethanol, cold crystallization filters, and washes with small amount of ethanol, filter, air-dry, get 3, the 4-dimethoxybenzeneacetonitrile.
3,3, the preparation of 4-dimethoxy-phenylethylamine (adding hydroamination reaction)
3,4-dimethoxybenzeneacetonitrile 3,4-dimethoxy-phenylethylamine
Operation: ammonia is fed in the refrigerative ethanol, survey content and reach 9%, get chloroethanol; With cholamine, 3,4-dimethoxybenzeneacetonitrile, active nickel drop in the autoclave, ventilate three times with hydrogen, logical hydrogen starts stirring to autoclave, be warming up to 90～110 ℃, reacted 2 hours, and be cooled to 40 ℃, exhaust, blowing, filter, filtrate recycling ethanol gets 3, the 4-dimethoxy-phenylethylamine, standby.
4, N-(2,3-dimethoxy-N-benzyl)-B-(3, the 4-Dimethoxyphenyl)-ethamine
The preparation of vitriol (condensation reaction)
Condensate sulfate
Operation: with 3,4-dimethoxy-phenylethylamine and 2, the 3-dimethoxy benzaldehyde mixes, and is heated to 105～110 ℃ of decompressions 1 hour.Condenses after concentrating is chilled to room temperature and drops into autoclave, adds ethanol, and active nickel seals back hydrogen exchange air three times, fills hydrogen institute, stir, be warming up to 65～70 ℃, insulation reaction 2 hours is chilled to 40 ℃, after the exhaust material is extruded, filter, reclaim ethanol, concentrated solution is chilled to room temperature.Transferring PH with 60% sulfuric acid is 2, and cold crystallization filters, and washes with small amount of ethanol, drains, and 80 ℃ of dryings get condensate sulfate, and are standby.
5, the preparation of chlorination palmatine (ring-closure reaction)
Operation: glacial acetic acid, anhydrous cupric sulfate, sodium-chlor, oxalic dialdehyde are dropped in the exsiccant retort, stir, temperature is 50～60 ℃ in the control, heats 30 minutes, adds condensate sulfate then, and temperature is 90～95 ℃ in keeping, and reacts 8 hours, is cooled to 60 ℃ of blowings.Reactant continues to be as cold as below 15 ℃, removes by filter mother liquor, and filter cake adds 2～3 times of 80～90 ℃ of hot water, stirs, and dissolving is chilled to 20 ℃, elimination water, and filter wash 2～3 times, filter is done.Filter cake adds the hot water that is equivalent to 4～6 times in condensation vitriol, adds 80～90 ℃ of the interior temperature of thermal control, and under agitation, adding yellow soda ash adjusting PH is 8.5～9, filtered while hot, and filter cake adds suitable quantity of water, and heat regulation PH is 8.5, filter wash 2～3 times, merging filtrate.Filtrate is heated to 60 ℃, and stirring and dripping HCl to PH down is soil, be cooled to below 15 ℃, and the leaching crystallization, 70～80 ℃ of oven dry get the chlorination palmatine.
6, the preparation of Fibrauretin (hydrogenation reduction)
Operation: chlorination palmatine, sodium acetate, ethanol, active nickel are dropped in the autoclave sealing, logical hydrogen ventilation 3 times, charge into hydrogen, start stirring, temperature is 85～90 ℃ in the control, reacted 4 hours, and be cooled to 60 ℃, after the exhaust, extrude material in the still, the filtering active nickel reclaims half volume ethanol, reheat pours one times of calorimetric distilled water after refluxing and dissolving, and places the result, suction filtration gets the Fibrauretin crude product.The ethanol of crude product and 3 times of amounts of crude product is dropped in the retort, and reflux is dissolved fully, and filtered while hot pours 3 times of 80～90 ℃ of hot water, and natural cooling crystallization is filtered, and uses 50% washing with alcohol, drains, and 70 ℃ of dryings promptly get the Fibrauretin finished product.
Claims (1)
1, a kind of synthesis preparation method of fibrauretine of antibiosis anti-inflammatory drug is characterized in that it synthetic realizes by following step:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510064486 CN1687064A (en) | 2005-04-18 | 2005-04-18 | Synthetic method for preparing fibrauretine of antibiosis anti-inflammatory drug |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510064486 CN1687064A (en) | 2005-04-18 | 2005-04-18 | Synthetic method for preparing fibrauretine of antibiosis anti-inflammatory drug |
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| CN1687064A true CN1687064A (en) | 2005-10-26 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973991A (en) * | 2010-11-23 | 2011-02-16 | 太仓浦源医药原料有限公司 | Preparation method of fibrauretine |
| CN102532130A (en) * | 2011-12-27 | 2012-07-04 | 广西中医学院 | Method for full chemical synthesis of fibrauretin anti-bacterial anti-inflammatory medicine |
| CN103408439A (en) * | 2013-07-01 | 2013-11-27 | 江苏省中国科学院植物研究所 | Chemical synthetic method of norbelladine |
| CN103570507A (en) * | 2013-11-13 | 2014-02-12 | 浙江理工大学 | Preparation method of 4-methylcatechol |
| CN105384650A (en) * | 2014-09-09 | 2016-03-09 | 中国石油化工股份有限公司 | Production technology of 3,4-dimethoxy phenethylamine |
| CN108358913A (en) * | 2018-02-28 | 2018-08-03 | 四川依科制药有限公司 | A kind of green synthesis process of rotundine sulfate |
| CN108484593A (en) * | 2018-05-15 | 2018-09-04 | 常州大学 | A kind of synthetic method of fibrauretine |
-
2005
- 2005-04-18 CN CN 200510064486 patent/CN1687064A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101973991A (en) * | 2010-11-23 | 2011-02-16 | 太仓浦源医药原料有限公司 | Preparation method of fibrauretine |
| CN102532130A (en) * | 2011-12-27 | 2012-07-04 | 广西中医学院 | Method for full chemical synthesis of fibrauretin anti-bacterial anti-inflammatory medicine |
| CN103408439A (en) * | 2013-07-01 | 2013-11-27 | 江苏省中国科学院植物研究所 | Chemical synthetic method of norbelladine |
| CN103570507A (en) * | 2013-11-13 | 2014-02-12 | 浙江理工大学 | Preparation method of 4-methylcatechol |
| CN105384650A (en) * | 2014-09-09 | 2016-03-09 | 中国石油化工股份有限公司 | Production technology of 3,4-dimethoxy phenethylamine |
| CN105384650B (en) * | 2014-09-09 | 2017-11-17 | 中国石油化工股份有限公司 | A kind of 3,4 dimethoxy-phenylethylamine production technologies |
| CN108358913A (en) * | 2018-02-28 | 2018-08-03 | 四川依科制药有限公司 | A kind of green synthesis process of rotundine sulfate |
| CN108484593A (en) * | 2018-05-15 | 2018-09-04 | 常州大学 | A kind of synthetic method of fibrauretine |
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