Title

Part 1. Synthesis of laureatin. Part 2. Synthesis of glycosphingolipids

Date of Completion

January 2008

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

Natural products are chemical substances found in nature that have distinctive pharmacological effects. Analogs of natural products prepared in the laboratory have also shown significant biological effects. Laureatin, a major metabolite of a red marine algae of the genus Laurencia nipponica, has shown potent activity as a mosquito larvicide. We are interested in examining the potential of laureatin and its analogs as insecticides for mosquito vectors transmitting malaria. Two previous syntheses of laureatin involved the formation of the 8-membered ether ring, followed by cyclization of the oxetane ring. Our approach utilized 2-methyleneoxetane as our scaffold for the preparation of the cyclic ether of laureatin.^ Another set of targets are the glycosphingolipids. Glycosphingolipids have been shown to modulate immune responses. KRN7000, an α-galactosyl ceramide, has proven to be an important tool for probing the role of CD1-mediated NKT cell activation. We synthesized of 4-deoxy-4-fluoro-α-galactosyl ceramide, an analog of KRN7000. This analog was found to stimulate murine NKT cells and the activity has been shown to be comparable to that of KRN7000. The synthesis of this analogue from glucose pentaacetate and N-Boc-serine Weinreb amide is described. ^

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