METHOD OF SYNTHESIS OF CEFAZOLIN Russian patent published in 2003 - IPC

FIELD: antibiotics, microbiology. SUBSTANCE: invention relates to production of cefazolin relating to semisynthetic antibiotic of cephalosporin order. Method involves acylation of 3-mehylmercapto-(5-methyl-1,3,4-thiadiazolyl-2-yl)-7- aminocephalosporanic acid with tetrazole-1-acetic acid esters in an aqueous medium in the presence of immobilized enzyme from E. coli followed by fractional precipitation of 3-methylmercapto-(5-methyl-1,3,4-thiadiazolyl-2-yl)-7-aminocephalosporanic acid and cefazolin and by recycling of 3-methylmarcapto-(5-methyl-1,3,4-thiadiazolyl-2-yl)-7-aminocephalosporanic acid. Acylation is carried out at temperature 10-30 C and pH gradient 7.8-6.2 using 3-methylmercapto-(5-methyl-1,3,4-thiadiazolyl-2-yl)-7- aminocephalosporanic acid in the initial concentration 20-40 g/l and the excess of tetrazole-1-acetic acid = (1.5-4) : 1. Polyenzyme complex of peptide hydrolases from the E. coli strain FU-99-S with predominant content of cefazolin synthetase with activity ≥ 300 mcmole/g x min by cefazolin synthesis and ratio above 8:1 by synthesis and hydrolysis of cefazolin is used as a biocatalyst immobilized in polyacrylamide gel as biomass cells of producer of cefazolin synthetase or enzyme isolated from biomass cells. Method provides the enhancement of output, effectiveness and quality of the end product. EFFECT: improved method of synthesis. 5 cl, 3 tbl, 7 ex