HYDROXYLATION AND N-DEMETHYLATION OF CLARITHROMYCIN (6-O-METHYLERYTHROMYCIN A) BY MUCOR CIRCINELLOIDES

In the course of studying the metabolism of clarithromycin (1, 6-O-methylerythromycin A, TE-031), (14R)-14-hydroxyclarithromycin (2) was isolated from human urine as a major and an active metabolite. For further pharmacological and toxicological studies on this metabolite, the authors obtained a significant quantity of 2 by the microbial transformation of 1 using Mucor circinelloides f. griseo-cyanus IFO 4563 super(3). A previous researcher isolated 15-hydroxyclarithromycin (3) as a minor metabolic product of 1 using the same microorganism. The authors have also isolated four minor metabolites of 1; 3, 16-hydroxyclarithromycin (4), N-demethylclarithromycin (5) and a 15-membered translactonization compound (6). The present paper describes the isolation and the structure determination of the metabolites 4 and 5.