Studies in Natural Product Synthesis and Catalysis of Pericyclic Reactions

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Our research program is a blend of fundamental and applied research in organic chemistry. The fundamental research focuses on the development of novel synthetic methods and the total synthesis of natural products. The applied portion of our research program is focused on the design and development of novel hybrid molecules for cancer treatment. In the fundamental research described in this proposal, we will pursue the synthesis of two natural products, palau'amine and virosaine. Palau'amine, a marine alkaloid with potent immunosuppresant activity, is a highly challenging target for chemical synthesis due to its density of functional groups and challenging stereochemistry. We are developing a Diels-Alder strategy to set the central carbocyclic ring and a conjugate addition/oxidative double-closure to close the trans-fused pyrrole amide/guanidine acetal portion of the molecule. Virosaine is a newly isolated Securinega alkaloid that is one of only a few molecules that has been proposed to arise biosyntheticallly by a [3+2] nitrone cycloaddition. We are developing a cascade sequence which will test the proposed [3+2] cycloaddition as the final step of our synthesis and will probe its relation to another Securinega alkaloid, flueggine A.