Preparation and biological evaluation of novel leucomycin analogs derived from nitroso Diels–Alder reactions

Abstract

A series of 10,13-disubstituted 16-membered macrolides was synthesized using nitroso Diels–Alder reactions of leucomycin A7. Despite the extensive constituent functionalities in leucomycin, the hetero cycloaddition reactions proceeded in a highly regio- and stereoselective fashion. Subsequent chemical modifications of the nitroso cycloadducts, including N–O bond reduction, were also conducted. Most leucomycin derivatives retained antibiotic profiles similar to leucomycin A7, and, in contrast to leucomycin itself, several exhibited moderate antiproliferative and cytotoxic activity.