Total synthesis of deinococcucins A-D and their isomeric derivatives via stereo- and regio-selective glycosylation: the discovery of a novel anti-angiogenic agent

Abstract

Deinococcucins are natural aminoglycolipids and are classified into A-D according to the structure of the fatty amines, which is linked with N-acetylglucosamine by a linker, d-glyceric acid. In this study, we completed the first total synthesis of dein-ococcucins A-D (1-4). Furthermore, we synthesized four new stereo- and regio-isomeric derivatives of deinococcucins (5-8). The main feature of these syntheses is the connection of glycosides and fatty amines, which uses glyceric acid as a linker, with glycosylation in a stereoselective and regioselective manner. Finally, synthesized deinococcucins and derivatives were evaluated for their biological activities, and derivative 8 showed the most potent anti-angiogenic effect in human umbilical vein endothelial cells (HUVEC) with IC50 = 9.05 mu M.