This proposal is directed towards the development of new approaches to the construction of naturaly occurring substances with important biological activity. The goal of the studies that we propose herein is not the total synthesis of complex organic molecules per se, but rather the development of new strategies in synthetic chemistry which will have applications beyond the construction of any particular class of natural products. Three distinct areas of research are outlined in this proposal: (1) the use of asymmetric radical cyclizations to control the absolute stereochemistry of carbon-carbon bond formation, (2) a variant of the de Mayo reaction which leads to the formation of medium rings and structurally complex organic molecules, and (3) the development of transannular radical cyclizations for the construction of complex organic molecules. The strategy that we have outlined for the synthesis of biologically active natural products using transannular radical cyclizations has counterparts in the Diels-Alder reaction, cationic polyene cyclization, and arene-olefin cycloaddition. More than one carbon-carbon bond and considerable stereochemical information is generated in a single synthetic operation. The constructions of the carbon skeleta of the anti-tumor compounds coriolin and taxol outlined in this proposal attest to the considerable potential of this methodology in the synthesis of medicinally important substances.