This program proposes to conduct studies on methods and strategies applicable to the synthesis of a number of natural products that display a range of physiological activity. In so doing, new methods of chemical synthesis and the mechanism by which these reactions occur will be explored. The success of such a program can lead to new methods of chemical synthesis and to new entries into drug design. Mitomycin C is currently used in Japan in the treatment of certain cancers. The recently isolated mitomycin congeners FR900482 and FR 66979, and the synthetic derivative FR973, have been shown in some instances to have superior activity compared to mitomycin C. New synthetic approaches to the formation and functionalization of the skeleton of these compounds, and hopefully the compounds themselves, will be explored. One group of compounds to be studied is the trichothecenes, mold metabolites derived from Fusarium species. Members of this class of compounds include anguidine (antitumor and mycotoxic agent), which is an intermediate in the preparation of T-2 toxin (mycotoxin and causative agent of alimentary toxic aleukia (ATA)), and FS-2 (embryotoxic agent). The fourth objective is the rational synthesis of scopadulcic acid B, an antiviral agent closely related to the structure of the antiviral and antimitotic agent, aphidicolin.
