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A high performance method for preparing cefaclor by enzyme catalysis

Cate:News Center Time:2025-10-11

  Cefaclor (Cefaclor) has a chemical name of (6R, 7R) -7- [ (R) -2-amino-2-phenylacetamido ] -3-chloro-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid monohydrate, is developed by American Gift company, has a wide antibacterial spectrum, has good antibacterial activity on pneumococci, streptococcus pyogenes, staphylococci, proteus mirabilis, colibacillus, pneumobacteria, haemophilus influenzae, diplococcus gonorrhoeae, anaerobic bacteria and the like, is clinically common oral cephalosporin, and has been a global-selling oral cephalosporin for many years.


  At present, cefaclor has two processes of chemical synthesis and enzymatic synthesis, wherein the chemical synthesis mostly adopts an acyl chloride method and a mixed anhydride method, the reaction steps are more, the conditions are harsh, and the pollution is serious. The enzyme method process is to synthesize cefaclor by using penicillin acylase to catalyze 7-amino-3-chloro-3-cephem-4-acid (7-ACCA) and D-phenylglycine methyl ester hydrochloride (D-PGM.HCl).


  The enzymatic process has the advantages of few reaction steps, simple operation, no toxicity, low cost and high yield, is a green synthesis technology with good application prospect, and has gradually replaced chemical synthesis technology in industry. However, the current industrial PGA has relatively low synthesis activity on the substrate 7-ACCA, long reaction time and relatively high substrate side chain ratio, and the development of penicillin acylase with high synthesis activity on the 7-ACCA substrate becomes an important direction of industrial development.


  Shanghai Kangxin Chemical Co.,ltd invents a method for preparing cefaclor by enzyme catalysis, which comprises the following steps:

7-amino-3-chloro-3-cephem-4-acid and D-phenylglycine methyl ester hydrochloride are used as substrates, and Oceanobacillus iheyensis-source penicillin amidase SEQ ID NO.1 or a mutant SEQ ID NO.3 thereof is used for catalyzing the synthesis reaction to obtain cefaclor, so that the synthesis efficiency and the substrate conversion rate of the cefaclor can be obviously improved.