Novel 16-membered macrolides modified at C-12 and C-13 positions of midecamycin A1 and miokamycin. Part 1: Synthesis and evaluation of 12,13-carbamate and 12-arylalkylamino-13-hydroxy analogues.

Design and synthesis of 16-membered macrolides modified at the C-12 and 13 positions are described. The compounds we report here have an arylalkylamino group attached to the C-12 position of the macrolactone. Both types of derivatives, 12,13-cyclic carbamates and non-carbamate analogues, were synthesized via 12-amino-13-hydroxy intermediates derived from 12,13-epoxide that was prepared by selective epoxidation at the C-12 and C-13 positions. 4'-Hydroxyl analogues were also prepared by acidic hydrolysis of a neutral sugar. These compounds were evaluated for in vitro antibacterial activity against respiratory tract pathogens. Some of these analogues exhibited an improved activity compared with the corresponding parent compound.