Total Synthesis and Biological Evaluation of Glycolipids Plakosides A, B and Their Analogs

The total synthesis of plakosides A (1) and B (2), and their designed analogs 3 – 10 was accomplished. The convergent strategy employed involved construction of the individual building blocks employing the Sharpless asymmetric dihydroxylation and the Charette asymmetric cyclopropanation reactions to introduce the desired configuration, followed by their couplings and final elaboration. Thus, key intermediates 12 – 14 were prepared in their optically active forms and joined through a glycosidation reaction and amide-bond formation to yield the target molecules after appropriate elaboration and final deprotection. The synthesized compounds 1 – 10 were evaluated for their immunosuppressive properties in vitro and found to be only modestly active.