STUDIES ON THE STABILITY OF DELTA(2) AND DELTA(3) CEPHEM ESTERS .2. COMPARATIVE STABILITY STUDIES OF DELTA(2) AND DELTA(3) CEPHEMS AT VARIOUS PHS AND THE DEGRADATION PROCESS OF DELTA(2) CEPHEM ESTERS

The instability of Delta(2) cephem prodrug-type ester (5a) under acidic conditions prompted us to investigate the comparative stability of Delta(3) and Delta(2) cephems at various pHs. The Delta(2) cephem ester 5a was found to show marked instability under neutral (pH 7) and acidic conditions (1 M HCl) compared with the Delta(3) cephem ester (4a). A comparative study between Delta(3) (4c) and Delta(2) cephem acid (5c) at pH 7 and in 1M HCl solution showed that the Delta(2) acid 5c was as stable as the Delta(3) acid 4c at pH 7, while 5c was less stable than 4c in 1M HCl. Isolation of the degraded compounds demonstrated that the C-4 ester moiety was hydrolyzed in the initial stage to afford 5c, which was further degraded to more polar substances, This instability was observed in other types of Delta(2) cephem esters (5d-f), Here we report comparative stability studies and elucidation of the degradation products.