This renewal proposal outlines five specific objectives in the chemistry and pharmacology of antitumor, antileukemic, antifungal and antibiotic natural products. Plans include chemical and biosynthetic investigations of naturally-occurring highly oxidized cyclohexanes, as well as total syntheses of complex quassinoids, the fungal metabolite LLZ-1220, and Beta-lactam structures such as thienamycin and the monobactams. Studies will also be initiated in collaboration with investigators at Vanderbilt University School of Medicine on the oxidative metabolism of Dilantin (diphenylhydantoin), a potent anticonvulsant and antiepileptic agent. Our long-term objectives include the preparation of new biologically active compounds and drug analogs for pharmacological evaluation.
