SYNTHESIS OF 6-O-METHYL-AZITHROMYCIN AND ITS KETOLIDE ANALOG VIA BECKMANN REARRANGEMENT OF 9(E)-6-O-METHYL-ERYTHROMYCIN OXIME

The synthesis of 6-O-methyl-azithromycin and its aza-ketolide analogue have been achieved by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methyl-erythromycin oxime 1. In contrast to the C14 ketolides like HMR 3647, the aza-ketolide turns out to be ina ctive, thus demonstrating that the addition of a 3 keto function and r ing expension, from 14 to 15 membered ring, could be deleterious for t he antibacterial activity, (C) 1998 Elsevier Science Ltd. All rights r eserved.