The objective of the work proposed herein is to establish the viability of a unique, organometallic-based polycyclization reaction as a tool for organic synthesis. In the long-term it is hoped that it will be possible to achieve total synthesis of a wide variety of biologically significant natural product structural types. A large number of such ultimate applications are suggested; the molecular targets include several sesquiterpene lactones with antitumor activities, a relatively new triquinane with significant carditoxic properties, a prominent member of the prostaglandin family which contains many molecules renowned for their physiological potency, and an alkaloid whose derivatives have been used for treatment of human cancers. In the short- term, it will be necessary to carefully define the limits of this potential applicability by careful experimentation.
The specific aims section outlines a regimen involving judicious choices of reaction conditions and substrates, variations in organometallic species, and alternative and more flexible precursors to some of the same intermediates on the reaction pathway.
