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A kind of method for preparing cephalexin

A technology of cephalexin and L-phenylglycine, which is applied in the field of preparation of cephalexin, can solve the problems of serious enzymatic hydrolysis reaction, large amount of side chain feeding, low product purity, etc., and achieve the effect of overcoming reverse reaction, improving product quality and improving conversion rate

Active Publication Date: 2015-08-26
NORTH CHINA PHARMA COMPANY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a new method for preparing cephalexin, so as to solve the problems of large amount of side chain feed, serious enzymolysis reaction, low product purity, high preparation cost and serious environmental pollution in the existing technology.

Method used

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  • A kind of method for preparing cephalexin
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  • A kind of method for preparing cephalexin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] 1) Take D-phenylglycine methyl ester sulfate solid (13.0g based on L-phenylglycine methyl ester), slowly add it to the 7-ADCA aqueous solution (100ml, mass concentration 15%), and take 30 to 120 minutes to ensure the system pH The value drops naturally, and ammonia is used to maintain the pH at 6.0-7.2; then 15g of specific penicillin acylase is added, and the reaction is started at 15-25°C.

[0058] 2) The time from the beginning of the reaction to the beginning of turbidity is recorded as A. When the reaction time reaches 2~3×A, start to slowly add 25ml of purified water, which takes 20 to 60 minutes. At the same time, use HPLC during the process of adding purified water. Method to judge the end of the reaction.

[0059] During the above 1)~2) operation, always use ammonia water to keep the pH of the system at 6.0~7.2;

[0060] So far, calculated based on the concentration of 7-ADCA detected by HPLC, the conversion rate of this reaction is 98%.

[0061] 3) After the reaction...

Embodiment 2

[0067] 1) Take D-phenylglycine methyl ester sulfate solid (17.5g based on L-phenylglycine methyl ester) and dissolve it in 40-60ml water to make D-phenylglycine methyl ester sulfate solution, and slowly add it to the 7-ADCA aqueous solution ( 120ml, mass concentration 12.5%), it takes 30-120min to ensure that the PH value of the system naturally drops, and ammonia water is used to maintain the pH at 6.0-7.2; then 20g of specific penicillin acylase is added, and the reaction is started at 15-25°C.

[0068] 2) The time from the beginning of the reaction to the beginning of turbidity is recorded as A. When the reaction time reaches 2~3×A, start to slowly add 40ml of purified water, which takes 20 to 60 minutes. At the same time, use HPLC during the process of adding purified water. Method to judge the end of the reaction.

[0069] During the above 1)~2) operation, always use ammonia water to keep the pH of the system at 6.0~7.2;

[0070] So far, calculated based on the 7-ADCA concentra...

Embodiment 3

[0077] 1) Take D-phenylglycine methyl ester sulfate solid (19.0g based on L-phenylglycine methyl ester) and dissolve it in 10-20ml water to make D-phenylglycine methyl ester sulfate suspension, slowly add it to the 7-ADCA aqueous solution Medium (150ml, mass concentration 10%), it takes 30 to 120 minutes to ensure that the pH of the system naturally drops, and ammonia water is used to maintain the pH at 6.0 to 7.2; then add 30 g of specific penicillin acylase, and start the reaction at 15 to 25°C , And use HPLC method to determine the end of the reaction.

[0078] During the above 1)~2) operation, always use ammonia water to keep the pH of the system at 6.0~7.2;

[0079] So far, calculated based on the 7-ADCA concentration detected by HPLC, the conversion rate of this reaction is 99%.

[0080] 3) After the reaction is terminated, the reaction solution is passed through an 80-mesh screen to obtain penicillin acylase and cephalexin suspensions, and the cephalexin suspension is filtere...

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Abstract

The invention discloses a method for preparing cefalexin. The method comprises the steps of charging a D-2-phenylglycine ester derivative and 7-ADCA (amino desacetoxy cephalosporanic acid) in a molar ratio of (1.15-1.6):1, and adding a catalyst penicillin acylase with amount of 1-2 times of amount of the 7-ADCA for acylation reaction, wherein the coded gene sequence of the penicillin acylase is shown as SEQIDNO:3. The method effectively overcomes reverse reaction during enzyme condensation reaction, so as to greatly reduce the using amount of side chains, avoid the phenomenon that more impurities are generated when high side chains are consumed, and solve the problem that the objective product is difficult to purify; and besides, the 7-ADCA conversion rate can be greatly improved to be up to more than 98%, the product quality is further improved and the production cost is reduced.

Description

Technical field [0001] The invention relates to antibiotic synthesis technology, in particular to a method for preparing cephalexin. Background technique [0002] Cephalexin, the English name Cephalexin, is a semi-synthetic β-lactam antibiotic with a broad-spectrum antibacterial effect. It has antibacterial effect on both gram-positive and gram-negative bacteria. Its mechanism of action is by inhibiting the cell wall Synthesize, swell the cell contents to break and dissolve, so as to achieve sterilization effect. [0003] The synthesis process of cephalexin mainly includes chemical synthesis and enzymatic synthesis. The chemical synthesis method is to mix an anhydride from L-phenylglycine ethyl deng potassium salt in dichloromethane solvent and react with carboxyl protected 7ADCA. Chemical condensation to obtain cephalexin. In the end, every 1kg of cephalexin will produce more than 10kg of three wastes. In this case, the enzymatic synthesis process has gradually received more at...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P35/04
Inventor 刘东杨梦德胡国刚甘平娟张锁庆魏阔杨宏利张文胜刘力强王新辉曹欢黄刚
Owner NORTH CHINA PHARMA COMPANY
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