THE DEGRADATION MECHANISM OF AN ORAL CEPHALOSPORIN - CEFACLOR

The degradation of cefaclor (1), an oral cephalosporin antibiotic, was studied at 37 degrees in a neutral aqueous medium by HPLC and H-1-NMR . Under these conditions, 1 underwent intramolecular aminolysis by the 7-side-chain NH2 group on the beta-lactam moiety to give a piperazine -2,5-dione. The most prominent peak in the HPLC profile oi. a degradat ion solution from 1 was isolated by prep. HPLC. Mechanistically, the f ormation of this degradation product cis-ll from 1 involves the contra ction from a six-membered cephem ring to a five-membered ring, which p resumably takes place via a common episulfonium ion intermediate 9 (se e Scheme). Loss of the Cl-atom from 3-chioro-3-cephem is a general rea ction subsequent to beta-lactam ring opening.