ORGANOMANGANESE REAGENTS IN ORGANIC SYNTHESIS

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This research proposal describes a series of experiments designed to probe the ability of organomanganese pentacarbonyl complexes to serve as reagents for the synthesis of structurally complex organic substances. The proposal is comprised of three sections. In the first, methodological studies are outlined. These include determination of the scope and limitation of the sequential insertion reaction, novel methodology for the preparation of highly functionalized manganese complexes, in particular glycosylmanganese complexes, and intramolecular variants of the sequential insertion reaction. The second section of the proposal describes the application of organomanganese reagents to the total synthesis of C-glycosyl substances tiazofurin (NSC-286193), selenazofurin, and pyrazofurin in optically active form. Tiazofurin and selenazofurin are synthetic C-nucleosides which possess potent antiviral and antitumor activity. For instance, both substances exhibit activity against Lewis lung carcinoma and L1210 and P388 leukemias in vivo. Pyrazofurin is a C-nucleoside isolated from Streptomyces candidus which has antitumor and broad spectrum antiviral activity. Pyrazofurin suppresses the replication of vaccinia, herpes simplex, measles, rhino and influenza viruses, and Friend and Rauscher leukemia virus in mice. Cultured Novikoff rat hepatome cells, HeLa cells and mouse L cells are also sensitive to pyrazofurin. The final section of the proposal describes preliminary studies of the utilization of organomanganese pentacarbonyl complexes for the synthesis of systems found in natural products such as C-arylated glycosyl compounds and polyether systems. The compounds synthesized during this investigation will serve as model compounds for the total synthesis of vineomycin B, pluramycin, chrysomycin B, lasolocid and monensin.