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Method for preparing cefalexin

A technology for cephalexin and L-phenylglycine, which is applied in the field of preparing cephalexin, can solve the problems of serious enzymatic hydrolysis reaction, large side chain feeding amount and high preparation cost, and achieves the effects of overcoming reverse reaction, improving product quality and improving conversion rate

Active Publication Date: 2014-05-21
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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  • Method for preparing cefalexin
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  • Method for preparing cefalexin

Examples

Experimental program
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Effect test

Embodiment 1

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

[0058] 2) Record the time from the beginning of the reaction to the appearance of turbidity as A. When the reaction time reaches 2-3×A, slowly add 25ml of purified water for 20-60 minutes. At the same time, HPLC is used during the process of adding purified water method to determine the end point 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, according to the calculation of the 7-ADCA concentration detected by HPLC, the conversion rate of this reaction is 98%.

[0061] 3) After the reaction is term...

Embodiment 2

[0067] 1) Dissolve D-phenylglycine methyl sulfate solid (17.5g as L-phenylglycine methyl ester) in 40-60ml of water to make D-phenylglycine methyl sulfate solution, and slowly add it to 7-ADCA aqueous solution ( 120ml, mass concentration 12.5%), it took 30-120min to ensure the natural drop of the pH value of the system, and maintain the pH at 6.0-7.2 with ammonia water; then add 20g of specific penicillin acylase, and start the reaction at 15-25°C.

[0068] 2) Record the time from the beginning of the reaction to the appearance of turbidity as A. When the reaction time reaches 2 to 3×A, slowly add 40ml of purified water for 20 to 60 minutes. At the same time, HPLC is used during the process of adding purified water method to determine the end point 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, according to the calculation of the 7-ADCA concentration detected by HPLC, the conversio...

Embodiment 3

[0077] 1) Dissolve D-phenylglycine methyl sulfate solid (19.0g as L-phenylglycine methyl ester) in 10-20ml water to make D-phenylglycine methyl sulfate suspension, and slowly add it to 7-ADCA aqueous solution Medium (150ml, mass concentration 10%), it takes 30-120min to ensure that the pH of the system drops naturally, and maintains the pH at 6.0-7.2 with ammonia water; then add 30g of specific penicillin acylase, and start the reaction at 15-25°C , and the HPLC method was used to judge the reaction end point.

[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, according to the calculation of the 7-ADCA concentration detected by HPLC, the conversion rate of this reaction is 99%.

[0080] 3) After the reaction is terminated, pass the reaction solution through a 80-mesh sieve to obtain penicillin acylase and cephalexin suspension, respectively, and filter the cephalexin suspension to obtain cephalexin coa...

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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] Cefalexin, the English name Cephalexin, is a semi-synthetic β-lactam antibiotic with broad-spectrum antibacterial effect on both Gram-positive and Gram-negative bacteria. Synthesized to make the cell content expand to rupture and dissolve, so as to achieve the bactericidal effect. [0003] The synthetic technique of cephalexin mainly contains two kinds of chemical synthesis and enzymatic synthesis. The chemical synthesis is to react with the carboxyl-protected 7ADCA after the mixed anhydride of L-phenylglycine ethyl Deng potassium salt in dichloromethane solvent. Chemical condensation to obtain cephalexin. Finally, every 1 kg of cephalexin produced will produce more than 10 kg of three wastes. In this case, the enzymatic synthesis process has gradually received more attention and research. Enzymatic synthesis t...

Claims

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Application Information

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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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