A formal synthesis of the glycosphingolipid, plakoside A

Date of Completion

January 2004

Keywords

Chemistry, Organic|Chemistry, Pharmaceutical

Degree

Ph.D.

Abstract

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. ^

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