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Method for efficiently synthesizing vinpocetine from vincamine

A technology of vinpocetine and vincamine, applied in the direction of organic chemistry and the like, can solve the problems of complicated operation, poor effect, difficult handling, etc., and achieve the effects of simplified reaction steps, high product yield and high acylation efficiency.

Inactive Publication Date: 2013-09-18
CHANGSHA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But this method has obvious disadvantages: 1) Concentrated H 2 SO 4 Oxidative, if the concentration is small, the effect of dehydration and water absorption is poor, if the concentration is high, it is easy to oxidize vinblastine; 2) The esterification reaction is an equilibrium reaction, and water removal measures must be taken during the reaction, otherwise, the reaction will not be complete
However, this method uses two Lewis acid-catalyzed reactions, and the ZnCl 2 , AlCl 3 It is difficult to handle in production and the operation is cumbersome, so it is not suitable for large-scale production. This research group has developed a new method for synthesizing vinpocetine from vincamine. This method uses Lewis acid phosphorus oxychloride as a catalyst-dehydrating agent. Dehydration and acyl chlorination are completed in one step, and then the esterification reaction of acyl chlorinated vinblastine and ethanol is carried out to synthesize vinpocetine

Method used

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  • Method for efficiently synthesizing vinpocetine from vincamine
  • Method for efficiently synthesizing vinpocetine from vincamine

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Add 35 g of potassium hydroxide and 800 ml of absolute ethanol to the three-necked flask, stir at 60°C to dissolve all the potassium hydroxide, then add 71 g of vincamine to the three-necked flask, heat and stir for 4.5 hours, and react on a thin-layer silica gel plate After the reaction is completed, replace the hot water in the water bath with cold water, stir to cool the reaction solution, slowly add glacial acetic acid, and monitor the pH value with pH test paper until the pH is 6. Let it stand for a period of time, filter out the crystals, wash once with an appropriate amount of 300 ml deionized water, rinse with pure water, and dry to obtain 68 g of vinblastine.

Embodiment 2

[0037]Weigh 110 g of vinblastine and put it into a three-necked bottle, measure 1600 ml of dichloroethane, and add 300 ml of phosphorus oxychloride into the bottle, connect the condenser tube and drying tube, adjust the temperature to 70 ° C, and heat and stir for 7 A thin layer of silica gel followed the reaction for hours. After the reaction was completed, the solvent was concentrated under reduced pressure to a minimum amount, the concentrated solution was transferred to a three-necked flask, magnetic stirring was turned on, and 400 ml of absolute ethanol was slowly added dropwise, and then stirred for 30 minutes after the drop was completed. Dilute triethylamine with absolute ethanol to about 60%, and slowly drop it into the three-necked bottle through the constant pressure funnel, and monitor the pH value with pH test paper until the pH value is 8. Continue stirring for 30 minutes after adjusting the pH value. Pour the solid-liquid mixture into a concentrated bottle, con...

Embodiment 3

[0039] Weigh 14 g of sodium hydroxide into a three-necked flask, add 800 ml of absolute ethanol, stir, and heat to 60°C. After the sodium hydroxide was completely dissolved, 36 g of vincamine was weighed and added into a three-neck flask, heated and stirred for 5 hours, and the reaction was followed by TLC. After the reaction is completed, cool to room temperature, slowly add glacial acetic acid, and monitor the pH value with pH test paper until the pH is 6. Let stand for a period of time, filter out the crystals, soak once in an appropriate amount of pure water, rinse with pure water, and dry to obtain 35.3 g of vincine.

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Abstract

The invention relates to a method for efficiently synthesizing vinpocetine from vincamine. The method is used for preparing the vinpocetine by three steps of reactions including vincamine hydrolysis, dehydration-acylating chlorination and esterification. In the method, a catalyst adopted in the vincamine hydrolysis reaction is strong base KOH or NaOH, a catalyst for the vincamine acid dehydration-acylating chlorination reaction is phosphorus oxychloride, and a catalyst for the esterification reaction between the acyl chloride compound and ethanol is sodium ethoxide or triethylamine. According to the method provided by the invention, Lewis acid phosphorus oxychloride is used as a catalysis-dehydration agent, the dehydration and acylating chlorination are finished by one-step coupling, and then the vinpocetine is prepared through the esterification reaction between the acyl chloride compound and ethanol; additional dehydration treatment is not required in the reaction, the efficiency of the dehydration and esterification reaction is high, and the product yield is over 90%; and the method is simple and convenient to operate and has better prospects in industrial application and development.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to a method for synthesizing vinpocetine from vincamine with high efficiency. Background technique [0002] Vinpocetine ( figure 1 ) is a derivative of vincamine, an alkaloid extracted and isolated from the plant Vinca minor of Apocynaceae. The compound was first developed by the Gedeon Richter Pharmaceutical Company in Hungary and launched in 1978. It has become one of the first-line drugs for the treatment and prevention of ischemic stroke and other diseases caused by cerebrovascular diseases in clinical practice. It has the effect of dilating small blood vessels in the brain, increasing the utilization rate of blood oxygen in the brain, and improving cerebral circulation. In addition, it can inhibit platelet aggregation, reduce blood viscosity, enhance red blood cell deformability, improve blood fluidity and microcirculation, promote brain tissue uptake of glucose, increase brai...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D461/00
Inventor 龚福春李灿杨荣
Owner CHANGSHA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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