Patent ID: 6319684
Filing Date: 2001-11-20
Classification: C12P

Abstract:
A process for preparing a cephalosporin of the formula ##STR2##wherein R.sub.0 is hydrogen or C.sub.1-3 alkoxy;Y is CH.sub.2, O, S or an oxidized form of S; andR.sub.1 is selected from the group consisting of H, OH, halogen, C.sub.1-3 alkoxy, C.sub.1-5 alkyl which is saturated or unsaturated, branched or straight, said alkyl being optionally substituted and optionally containing one ore more heteroatoms, C.sub.5-8 cycloalkyl, said cycloalkyl being optionally substituted and optionally containing one or more heteroatoms, optionally substituted aryl, optionally substituted in heteroaryl, and optionally substituted benzyl;which comprises(a) extracting an N-substituted cephalosporin into an organic solvent from a fermentation broth of a cephalosporin producing microorganism, said fermentation having been conducted in the presence of a dicarboxylic acid cephalosporin N-side chain precursor, to obtain an organic solvent extract containing the N-substituted cephalosporin:(b) back-extracting the N-substituted cephalosporin into an aqueous phase, thus obtaining an aqueous phase containing said N-substituted cephalosporing and(c) treating said aqueous phase containing N-substituted cephalosporin with a dicarboxylate acylase to convert said N-substituted cephalosporin into the compound of formula (I); and(d) optionally isolating said compound of formula (I) by crystallization;wherein the fermentation broth extracted in step (a) or the aqueous phase containing N-substituted cephalosporin or the compound formula (I) in step (c) is incubated at a pH lower than 4 and a temperature of 60.degree. C. or higher.