Asymmetric Organocatalytic Cascade Reactions:
Applications toward the Synthesis of Complex Natural Products
Start date: Jul 9, 2012,
End date: Jul 8, 2014
"To address the current gap in the literature in defining a suitable synthetic route toward the pharmaceutically and structurally unique cytotoxic natural products, the daphniyunnines, we wish to develop the requisite methods and strategies during this fellowship. Using novel, synthetically flexible and powerful, enantioselective organocatalytic cascade reactions will facilitate our goals in this project. Specifically, we propose to develop an novel, asymmetric organocatalyst-controlled cascade Michael-Horner-Wadsworth-Emmons reaction and a subsequent gold(I)-catalysed hydroalkylation. This would establish a novel, powerful and broadly applicable organocatalytic asymmetric strategy toward this moiety. The second objective is to address our ability to access the complex natural products via a common divergent intermediate. To accomplish this, a cascade Michael-aldol condensation reaction will yield a common advanced tetracyclic intermediate which be further elaborated toward the daphniyunnine natural products and additional analogues. This will secure sufficient quantities to fully determine the therapeutic potential of these molecules. This will enable rapid entrance toward structurally intricate intermediates and would ultimately have a profound impact in the understanding of the power of organocatalytic cascade methods in organic synthesis."
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