AN ENZYMATIC PROCESS FOR PREPARING BETA-LACTAMS

摘要

An enzymatic process under kinetical control for preparing ß-lactams, by coupling the 7-amino group of 7-ACA with the carboxylic function of TZH activated as methyl- or ethylester. The process comprises using a penicillin amidase or a-amino acid esterase as free enzyme or in any suitable immobilised form; applying at least 100 mmol/l 7-ACA, applying TZH activated as ester a 1 - 3 fold molar ratio, and adjusting the pH to 6.0 - 8.0 and the temperature to 0 - 30°C. For direct 3-processing of the enzymatically synthesised TZ-7-ACA with heterocyclic thiols in aqueous solution at pH 6.0 - 8.5 and 50 - 75°C a dark brown colour is formed. Surprisingly this can be avoided, if 7-ACA is removed almost completely, advantageously by salting out the 7-derivative of 7-ACA. In said process the heterocylic thiol is MMTD or 2MTD and the formed product is cefazolin or ceftezol.