This proposal will initially focus on the development of a new carbosilation reaction which is catalytic in palladium or nickel. Once optimized, this procedure will allow for the rapid and stereodefined synthesis of di-, tri-, and tetra-substituted olefins commonly found in important natural products. More specifically, the carbosilation reaction will be used in a highly convergent synthesis of neocarzinostatin chromophore analogues. These analogues, when assayed for biological activity / DNA cleaving ability, may yield information essential to the rational development of other neocarzinostatin congeners showing enhanced activity. Finally, the first total synthesis of the chromophore of the antitumor antibiotic neocarzinostatin will be a goal of technical merit.
