Synthesis of natural and unnatural ligands for NKT cells and cross-metathesis of exocyclic enones

Date of Completion

January 2008


Chemistry, Biochemistry




α-Galactosylceramides have gained considerable attention due to their ability to modulate immune responses. KRN7000, an unnatural glycosphingolipid, has undoubtedly enhanced the understanding of NKT cell function. There has been intense interest in identifying natural and unnatural ligands for NKT cells, because they may offer new approaches to treating viral and bacterial infections, cancer and autoimmune conditions. The synthesis of glycolipids is imperative for studying the influence of glycolipid structure on immune response. This thesis describes the design, construction, and/or potencies (relative to KRN7000) of novel glycolipids. ^ Our interest in strained heterocycles led us to examine the cross-metathesis of α-methylene-β-lactones. The remarkable efficiency of these strained systems in cross-metathesis reactions led us to explore other classes of α-methylene lactones. Herein, the disparate reactivity of four classes of enoates in the cross-metathesis reaction is described. ^