This proposal requests funding for replacement of a Varian XL- 200 NMR with a Varian VXR-300 superconducting high resolution FT NMR. This instrument would meet critical needs for walk-on 1H and 13C spectroscopy, broad-band capabilities, and 2D NMR. The major user group consists of faculty form the Department of Medicinal Chemistry and Chemistry. Dr. Cassady will elucidate the structures and study the chemistry and molecular pharmacology of bioactive natural products. Dr. Boger and Dr. Fuchs will study the total synthesis of complex natural products with antitumor and other biological activity. Dr. Byrn will examine the interaction of drugs with DNA and RNA templates. Dr. Chang will study the chemistry of alkylation of DNA in vitro and the chemistry of alkylated oligonucleotides. Dr. Schwab will explore the mechanism and stereochemistry of key enzymatic processes including metabolism of fatty acids and dehydration reactions.