CN103570599A - Preparation method of prostaglandin A1 - Google Patents
Preparation method of prostaglandin A1 Download PDFInfo
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- CN103570599A CN103570599A CN201310562300.4A CN201310562300A CN103570599A CN 103570599 A CN103570599 A CN 103570599A CN 201310562300 A CN201310562300 A CN 201310562300A CN 103570599 A CN103570599 A CN 103570599A
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- prostaglandin
- tetrahydrofuran
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Abstract
The invention provides a preparation method of prostaglandin A1. The preparation method comprises the steps of adding alprostadil and tetrahydrofuran at room temperature and stirring, filling hydrogen chloride gas, heating to 55-65 DEG C, reacting for 5-7 hours, adding active carbon and decolorizing for 30min, filtering to remove the active carbon, pressurizing mother liquor to remove a solvent, adding isopropyl alcohol to residual materials, dropping petroleum ether at 40-45 DEG C, slowly reducing temperature to be less than 10 DEG C, standing and crystallizing for 5-6 hours, and carrying out suction filtering to obtain a white solid prostaglandin A1. The preparation method implements an elimination reaction under an acid condition, and is moderate in reaction condition; the preparation method implements purification by recrystallization instead of chromatographic column separation, and is simple and quick to operate, high in product purity and is favorable for research on alprostadil.
Description
Technical field
The invention provides a kind of preparation method of PGA1.
Background technology
Prostaglandin(PG) is to be present in the actives with multiple physiological action that the class unsaturated fatty acids in animal and human's body forms, and nineteen thirty is strangled discovery especially.By its structure, prostaglandin(PG) is divided into the types such as A, B, C, D, E, F, G, H, I.Dissimilar prostaglandin(PG) has different functions, as PGE energy diastole bronchial smooth muscle, reduces aeration resistance; The effect of prostaglandin F is contrary.
Prostaglandin E1, has another name called prostaglandin E1, and English name prostaglandin E1. molecular formula is C
20h
34o
5, chemical name 11(a), 15(s)-anti-prostenoic acid of bis-hydroxyl-9-ketone-13-, for usp and bp record, and is the medicine that 2010 editions pharmacopeia of the People's Republic of China (PRC) are recorded, structural formula is:
This medicine is used for the treatment of the four limbs tranquillization pain that four limbs ulcer that chronic arteria occlusion disease causes and tiny blood vessels cycle penalty cause, improves cardiovascular and cerebrovascular microcirculation disturbance.The postoperative anti-bolt treatment of organ transplantation, in order to suppress the thrombosis in grafting vessel.In Congenital Heart Disease patent ductus arteriosus, in order to alleviate hypoxemia, keeps conduit blood flow with the operative treatment of awaiting a favorable opportunity.
In the production of Prostaglandin E1 (prostaglandin E1), PGA1 is one of important impurity wherein.At present the synthetic employing Prostaglandin E1 of PGA1 room temperature reaction 60 hours in the mixed solvent of tetrahydrofuran (THF) and water one to one, obtains PGA1 through chromatography column separation.Such shortcoming is that the reaction times is oversize, and side reaction is many, and aftertreatment is complicated, inferior separating effect.Synthetic route is:
Summary of the invention
The preparation method who the object of this invention is to provide a kind of PGA1 eliminates reaction under acidic conditions, and reaction conditions is gentle, with recrystallization, replace chromatography column separation to purify, easy and simple to handle quick, product purity is high, to the research of Prostaglandin E1, provides effective help.
Concrete preparation method of the present invention is as follows: under room temperature, add Prostaglandin E1, tetrahydrofuran (THF) to stir, pass into hydrogen chloride gas, be warming up to 55-65 ℃, reaction 5-7 hour, add activated carbon decolorizing 30 minutes, filtering gac, solvent is drained in mother liquor pressurization, and remaining species add Virahol, at 40-45 ℃, drip sherwood oil, slow cooling to 10 ℃ following standing crystallization 5-6 hour, suction filtration, obtains white solid PGA1.
Prostaglandin E1 wherein: tetrahydrofuran (THF): hydrogenchloride: gac: Virahol: sherwood oil=1:9:0.2:0.05:2:10(weight ratio) synthetic route is:
The present invention be take Prostaglandin E1 as raw material, passes into hydrogen chloride gas backflow and eliminate reaction in tetrahydrofuran (THF), and through Virahol-sherwood oil, refine and obtain PGA1, reaction times 5-7 hour, yield 65-70%, product purity is greater than 98.5%.This reaction conditions is gentle, and easy and simple to handle, the method has improved products production efficiency, workable, is conducive to prostaglandin(PG)
The preparation of A1.
Embodiment
Embodiment 1
In reaction flask, add 500mg Prostaglandin E1,5ml tetrahydrofuran (THF), stir 10 minutes, pass into hydrogen chloride gas 20 minutes, be warming up to 55-65 ℃, react 5 hours.Add 0.025 gram of insulation of gac 30 minutes, heat filter, filtrate decompression steams solvent, remaining species add 2.5ml Virahol to be warming up to 40 ℃ of slow sherwood oil 15ml slow cooling to 10 ℃ following standing crystallization 5 hours that drip, suction filtration obtains light yellow solid 313mg, yield 66%, purity is greater than 98.5% embodiment 2
In reaction flask, add 1g Prostaglandin E1,10ml tetrahydrofuran (THF), stir 10 minutes, pass into hydrogen chloride gas 30 minutes, be warming up to 55-65 ℃, react 6.5 hours.Add 0.05 gram of insulation of gac 30 minutes, heat filter, filtrate decompression steams solvent, remaining species add 5ml Virahol to be warming up to 40 ℃ of slowly dropping sherwood oil 30ml slow cooling to 10 ℃ following hold over night crystallizatioies, suction filtration obtains light yellow solid 664mg, yield 70%, and purity is greater than 98.5.
It should be noted that: the foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, its technical scheme that still can record previous embodiment is modified, or part technical characterictic is wherein replaced on an equal basis.
Within the spirit and principles in the present invention all, any modification of making, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (1)
1. a preparation method for PGA1, is characterized in that at room temperature adding Prostaglandin E1, tetrahydrofuran (THF) to stir, and passes into hydrogen chloride gas, be warming up to 55-65 ℃, reaction 5-7 hour, adds activated carbon decolorizing 30 minutes, filtering gac, solvent is drained in mother liquor pressurization, remaining species add Virahol, at 40-45 ℃, drip sherwood oil, slow cooling to 10 ℃ following standing crystallization 5-6 hour, suction filtration, obtains white solid PGA1; Prostaglandin E1 by weight wherein: tetrahydrofuran (THF): hydrogenchloride: gac: Virahol: sherwood oil=1:9:0.2:0.05:2:10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310562300.4A CN103570599B (en) | 2013-11-11 | 2013-11-11 | Preparation method of prostaglandin A1 |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310562300.4A CN103570599B (en) | 2013-11-11 | 2013-11-11 | Preparation method of prostaglandin A1 |
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| CN103570599A true CN103570599A (en) | 2014-02-12 |
| CN103570599B CN103570599B (en) | 2015-05-06 |
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| CN201310562300.4A Active CN103570599B (en) | 2013-11-11 | 2013-11-11 | Preparation method of prostaglandin A1 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3632627A (en) * | 1968-01-05 | 1972-01-04 | Smith Kline French Lab | Glyceride derivatives of prostaglandins |
| US3887587A (en) * | 1972-04-17 | 1975-06-03 | Pfizer | Synthesis of prostaglandins of the one-series |
| CN101581702A (en) * | 2008-05-13 | 2009-11-18 | 上海万特医药科技有限公司 | Method for controlling quality of alprostadil injection |
-
2013
- 2013-11-11 CN CN201310562300.4A patent/CN103570599B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3632627A (en) * | 1968-01-05 | 1972-01-04 | Smith Kline French Lab | Glyceride derivatives of prostaglandins |
| US3887587A (en) * | 1972-04-17 | 1975-06-03 | Pfizer | Synthesis of prostaglandins of the one-series |
| CN101581702A (en) * | 2008-05-13 | 2009-11-18 | 上海万特医药科技有限公司 | Method for controlling quality of alprostadil injection |
Non-Patent Citations (2)
| Title |
|---|
| J. E. PIKE 等: "Prostanoic Acid Chemistry", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| YOKOYAMA SHOKO等: "Effect of lysophosphatidylcholine on acid-catalyzed dehydration (degradation) of prostaglandin E1", 《MATERIAL TECHNOLOGY》 * |
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| CN103570599B (en) | 2015-05-06 |
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