Novel azalides derived from 16-membered macrolides. III. Azalides modified at the C-15 and 4″ positions: Improved antibacterial activities

Abstract The design and synthesis of 16-membered azalides modified at the C-15 and 4″ positions are described. The compounds we report here are characterized by an arylpropenyl group attached to the C-15 position of macrolactone and a carbamoyl group at the C-4″ position in a neutral sugar. Introduction of alkylcarbamoyl groups to the C-4″ position was regioselectively achieved by unique and convenient methods via acyl migration. As a result of optimization at the C-3 and 15 positions, several compounds were found to have potent activity against mef - and erm -resistant bacterial strains. These results suggest that 16-membered azalides could be promising compounds as clinical candidates.