Degradation, structure and some derivatives of cephalosporin N

Abstract

Cephalosporin N is hydrolyzed by hot dilute acid to a penilloic acid, from which penicillamine may be obtained by treatment with mercuric chloride. More vigorous hydrolysis results in the liberation of D-alpha-aminoadipic acid. Oxidation of the penilloic acid with bromine water yields penicillaminic acid and a neutral aldehyde. The latter was oxidized with silver oxide to an alpha-aminoadipylmonoglycine. The pK of the amino group of this compound indicates that alpha-aminoadipic acid is linked to glycine through its delta-carboxyl group. It is concluded from these results that cephalosporin N is probably (D-4-amino-4-carboxy-n-butyl) penicillin. Cephalosporin N is transformed to a penillic acid in aqueous solution at pH 2.7. The penillic acid reacts with mercuric chloride to form a penillamine which was isolated as a crystalline S-benzyl derivative. Cephalosporin N reacts with certain acid chlorides, acetic anhydride, and phenyl isocyanate, to form derivatives which contain no free amino group. These derivatives are more active against Staphylococcus aureus and less active against Salmonella typhi than cephalosporin N itself.