This proposal outlines the catalytic asymmetric synthesis of the diterpene saudin. Saudin is a novel and densely functionalized caged bis(ketal) possessing significant in vivo hypoglycemic activity in mice and rats. A key component of this synthesis will be the use of catalyst control to set three of the five stereocenters not associated with the ketal system, including those present at the two quaternary carbons in the natural product. To accomplish the proposed route, a new metal-catalyzed carboxyacetoxylation of unactivated olefins will be developed and applied to the generation of the beta-hydroxy gamma-lactone moiety contained in the core structure. Additionally, this project will serve to further expand the scope of the recently reported enantioselective Tsuji allylation from the Stoltz laboratories through its application to the regio- and diastereoselective allylation of an extended enolate system. By using saudin as a platform for the discovery and development of the reactions described above, new methodology of significant utility to the synthetic community will be generated. ? ? ?
