Total Synthesis of Phomactins with Transition Metal Carbene Complexes

Michigan State University, East Lansing MI

Investigators

Abstract

The focus of this project is on the total synthesis of the phomactin family of natural products. Specifically this involves the synthesis of Phomactins A, B, B1, C, D, E, F, G and H, all platelet activating factor antagonists. The two key steps in the strategy involve the cyclohexadienone annulation reaction of Fischer carbene complexes with alkynes and the ring closing metathesis reaction with Grubbs carbene complexes. Since most of the phomactins have not been previously synthesized, the conversion of the key bicyclo[9.3.1]pentadecane to each of the targets will require the exploration of new territory and undoubtedly the development of new chemistry as well as the testing of hypotheses formulated from a consideration of probable biosynthetic pathways. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor William D. Wulff in the Department of Chemistry at Michigan State University. Professor Wulff's research efforts are concentrated on the development of the chemistry of Fischer carbene complexes for the advancement of the field of organic synthesis. The successful development of the proposed chemistry will contribute to the discovery and production of new products with societal benefits by the pharmaceutical, biotechnology, and agrochemical industries.