Studies on the Pyrrolizidine Antitumor Agent, Clazamycin: Interconversion of Clazamycins A and B

Clazamycin, a novel pyrrolizidine antitumor antibiotic, exists in aqueous solution as a mixture of two epimers, clazamycins A and B [1A, 1B], the ratio of which is pH dependent. Several lines of evidence are presented, including the results of trapping experiments and a study demonstrating base promoted interconversion of the two forms, that implicate an azacyclooctenone species [3] as an intermediate in the interconversion process. This result supports a previous observation, that the C6a carbinolamidine hydroxyl of clazamycin is unreactive towards nucleophiles and may be significant in helping to elucidate the mechanism of action of this antibiotic.