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43210-GB1
Regioselective Synthesis of Functionalized Furanones and Dihydropyranones by Olefin Metathesis

Kevin J. Quinn, College of the Holy Cross

Five- and six-membered lactones and ethers are common structural components of chemically and biologically significant natural products. We have developed a concise approach to synthesis of allyl 5H-furan-2-ones by size-selective ring-closing metathesis (RCM) of substituted 1,5-hexadien-3-yl acrylates and examined in situ cross metathesis (CM) of RCM products as an efficient and flexible method for the construction of highly functionalized furanones. We have examined the scope of the reaction and optimized reaction parameters in the context of a convergent synthesis of squamostolide, a bioactive member of the Annonaceous acetogenin family of natural products. Our current goal is to extend this methodology to the synthesis of dihydropyranone systems by RCM of 1,5-hexadien-3-yl vinyl acetates. This approach has been shown to be feasible with metathesis being accompanied by a desirable alkene isomerization. We are studying this reaction in detail for implementation in a total synthesis of boronolide, an antimalarial agent isolated from the root of a South African tree. This research has provided a training ground for promising scientists, and our work on squamostolide was published recently in Tetrahedron.

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