New Methods for Synthesis of Bioactive Terpenes

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This research program is being funded by the Synthetic Organic Chemistry Program. Dr. Pearson will develop new synthetic reagents based upon transition metal-olefin complexes. These complexes facilitate the construction of complicated ring systems found in the materials used by modern agriculture. This research revolves around the use of polyolefin-transition metal complexes as reactive intermediates for the construction of quaternary carbon centers. The methodology developed during these studies is to be applied in total synthesis of a number of biologically active terpenoid natural products. Cyclohexadienyliron complexes are to be used in the synthesis of trichothecenes such as trichodermol and verrucarol, and in synthesis of the diterpenoids stemodinone and aphidicolin. Each of these classes of compound show antibacterial, antifungal and/or antiviral activity. Newly discovered reactions of dienyl- and diene iron complexes, in which a pendant olefin is coupled to the organometallic unit in a carbon-carbon bond forming process are to be studied in detail. The scope and synthetic applications of these and related reactions will be investigated. A new approach to the synthesis of taxane derivatives will be investigated. These compounds, in particular taxol, show exceptional promise as antitumor agents. The synthetic approach described in this proposal aims to set in place the major part of the carbon skeleton via the reaction of a highly substituted tin enolate with tricarbonyl(l,3-dimethyl-4-methoxycyclohexadienyl)iron hexafluorophosphate, followed by an internal pinacol reaction to set in place the eight-membered ring.