Total Synthesis of Dhilirolide L

California Institute Of Technology, Pasadena CA

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Abstract

? DESCRIPTION (provided by applicant): The total synthesis of natural products drives the discovery of new therapeutics by inspiring innovation in synthetic methods. The methods that have been investigated and perfected since the nineteenth century are utilized daily in the synthesis of medically relevant small molecules. This research proposal describes a natural product synthesis project that relies on the development of the surrounding synthetic methodology. Specifically, the proposal outlines a synthetic route to two natural products in the dhilirolide family, dhilirolide M and L. These compounds are meroterpenoids, which are mixed polyketide-terpenoid natural products that are produced by filamentous fungi and contain unprecedented structural motifs. Dhilirolides have strong activity against Trichoplusia ni, a significant agricultural pest. This work will expand on the scope of an asymmetric allylic alkylation reaction developed by the Stoltz group. The specific aims are: 1) Expansion of the asymmetric allylic alkylation methodology to include chiral alcohol-containing allyl carbonates, 2) Total synthesis of Dhilirolide L; Construction of the 6-5-5 bridged core, and 3) Total synthesis of Dhilirolide L; Intramolecular Diels-Alder reaction and final modifications. Ultimately, the development of these techniques will culminate in the synthesis of this natural product and represent a route to similar structures.