Synthesis of diene ceramides with organozirconium reagents.

Abstract

Ceramide serves as a precursor to sphingomyelins and glycosphingolipids, and as an important intermediate in the de novo biosynthesis. Ceramide will act as second messenger in cell systems to induce programmed cell death (apoptosis). Ceramide is composed of a sphingosine backbone and fatty acid linked in an amide bond, and its structural variations have been modified and synthesized by many research group. The diene ceramide, unusual analogues of ceramide with a conjugated diene may have higher reactivity than other novel ceramide in mitochondria by facilitated oxidation at C3. One of the most important synthetic methodologies for diene ceramide was organozirconocene hydrochloride (Schwartz reagents) used for forming long chain dienyl sphingosine backbone. The organozirconocene complexes are also known for the transmetalation with other metal complexes for further nucleophilic additions. In this thesis, the synthesis of diene ceramide with chiral aldehyde for sphingosine head group and organozirconocene complexes will be described.