A formal synthesis of the glycosphingolipid, plakoside A

Glycosphingolipids are ubiquitous components of eukaryotic and prokaryotic organisms. They are biologically important molecules believed to be involved in all aspects of cell regulation, and cell modulation. ^ Plakoside A, a glycosphingolipid isolated from a marine sponge Plakortis simplex, has been shown to possess immunosuppressive activity. Moreover, studies show it to be inactive in an MTT assay for cytotoxicity. Thus, plakoside A may represent a novel, non-cytotoxic class of immunosuppressants with potential therapeutic applications and, as such, is a significant synthetic target. A formal synthesis of plakoside A is presented. Key features of our strategy include the use of Charette asymmetric cyclopropanation and enzyme catalyzed dynamic kinetic resolution. The synthesis of the sphingoid base exploits a serine-derived Weinreb amide, while the acyl chain is built from cyclooctadiene.