Synthesis and antibacterial activity of (9S)-9-dihydroclarithromycin.

Clarithromycin1* (1, 6-O-methylerythromycin A, A-56268, TE-031) is a new macrolide currently undergoing clinical development. The excellent properties2) of 1 make it attractive for further synthetic modifications. It is knownthat, reduction of the 9-keto group of erythromycin A (2), for example with sodium borohydride, gives the corresponding secondary alcohol, predominantly as the 9(S) epimer, known as 9-dihydroerythromycin (3)3~5). Although 3 has less antibacterial activity than erythromycin6), the 9-hydroxyl group provides a handle for further chemical transformations7) to producecompounds with improvedactivities over 3. The present paper describes the preparation and antibacterial activity of the analogous reduction product of 1 using nucleophilic hydride.