Method for synthesizing cefprozil through enzymatic method

Abstract

The invention relates to a method for synthesizing cefprozil through an enzymatic method. According to the method, a cefprozil parent nucleus, D-para hydroxybenzene glycine methyl ester and / or D-para hydroxybenzene glycine ethyl ester, water and penicillin acylase react at the temperature of 10 DEG C-25 DEG C to obtain a crude cefprozil product and enzyme reaction mother liquor, the temperature is controlled to be 0 DEG C-15 DEG C, a pH value is controlled to be 0.2-0.8, N,N-dimethyl formamide is added, the mixture is stirred uniformly, a seed crystal is added for crystal growing, the pH value is adjusted to be 5.5-6.5, and the temperature is controlled to be 10 DEG C-30 DEG C to obtain a cefprozil N,N-dimethyl formamide compound; the temperature is controlled to be 0 DEG C-25 DEG C, water and the cefprozil N,N-dimethyl formamide compound are added into a reactor, the mixture is stirred for crystal transformation for 1-4.5 h, and then filtering, washing, swabbing-off and drying are carried out to obtain a finished cefprozil product. The cefprozil is high in product yield and high in purity, appearance is white, the preparing method is simple and easy to implement, the condition is mild, and the method is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for enzymatically synthesizing cefprozil. Background technique [0002] Cefprozil is a third-generation oral broad-spectrum cephalosporin antibiotic, which was developed by Bristol-Myers Company of the United States and the Tokyo Research Institute, and was approved by the FDA in December 1992. There are many ways to synthesize cefprozil, but before this century, they were all chemical synthesis methods. The preparation process used many raw materials and auxiliary materials, and a large amount of solvents such as dichloromethane and acetone were used. The reaction conditions were also relatively harsh, often requiring -50 Low temperature below ℃, high cost and heavy pollution. After entering the 21st century, with the development of biotechnology and the breakthrough of enzyme gene modification technology, the use of biosynthesis technology to replace trad...

AI Technical Summary

Problems solved by technology

There are many ways to synthesize cefprozil, but before this century, they were all chemical synthesis methods. The preparation process used many raw materials and auxiliary materials, and a large amount of solvents such as dichloromethane and acetone were used. The reaction conditions were also relatively harsh, often requiring -50 Low temperature below ℃, high cost and heavy pollution