Chemical modification of erythromycins. VI. Structure and antibacterial activity of acid degradation products of 6-O-methylerythromycins A.

Erythromycin A, a useful macrolide antibiotic, is extremely unstable to acid and whenadministered orally undergoes dehydration in vivo to anhydroerythromycin A, an inactive 6,9; 9,12-spiroketal metabolite.1} In preceding paper,2) we have reported that 6-0-methylerythromycin A (1) was more stable to acid than erythromycin A due to the presence of 6-O-methyl group, which blocks the formation of 6,9; 9, 12-spiroketal derivative.Nevertheless, 1 loses gradually its antibacterial activity in dilute HC1solution.In present paper we describe the structure and antibacterial activity of the degradation products of 1 and its derivatives under acidic conditions.When1 was allowed to stand in aqueous acid solution (0.2% HC1 or 9% AcOH), a cleavage of