Design and synthesis of novel leucomycin analogues modified at the C-3 position. Part II: 3-O-(3-Aryl-2-propenyl)leucomycin analogues Original Research Article

The design and synthesis of 16-membered macrolides modified at the C-3 position are described. Starting from fully protected intermediate (5), appropriate modifications including Heck reaction were performed to furnish 3-O-(3-aryl-2-propenyl)leucomycin A7 analogues (9a–9m). These leucomycin A7 derivatives showed improved in vitro antibacterial activities against clinically important pathogens including erythromycin-resistant Streptococcus pneumoniae (ERSP). SAR analysis of derivatives modified at the C-3 and C-3″ positions suggested that single modification at C-3 or C-3″ was effective for in vitro antibacterial activity.