IMPROVED PROCESS FOR THE FERMENTATIVE PRODUCTION OF CEPHALOSPORIN

摘要

The present invention relates to a novel process for the preparation of cephalosporins having been deacylated at the 7-amino group, by fermentation of a cephalosporin producing microorganism in the presence of a side chain precursor, extraction of the N-substituted cephalosporin compound as present in the fermentation broth or fluid to an organic solvent, back extraction of the N-substituted cephalosporin compound to water, treatment of the aqueous phase with a dicarboxylate acylase and isolation of the crystalline cephalosporin compound according to formula (1) from the conversion solution, characterized in that the fermentation broth or fluid is incubated at acidic conditions and an elevated temperature prior to extraction of the N-substituted cephalosporin compound to an organic solvent. Further improvements of the process are obtained by washing the first organic solvent extract with acidified water and/or by extraction of the side chain to an organic solvent and/or by treating an aqueous cephalosporin solution produced at one or more stages in the process of the invention with carbon dioxide.