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Cyclopentannulation of Conjugated Enones and Synthesis of (--)-Viridin

  • Author(s): Del Bel, Matthew
  • et al.
Abstract

The work described herein is a culmination of synthetic studies in the development of a novel methodology for the cyclopentannulation of conjugated enones and the synthesis of the natural product viridin. The first chapter describes a methodology that uses methyl 3-( tert- butyldimethylsilyloxy)-2-diazo-3-butenoate as a bifunctional reagent. This reagent first performs a Mukaiyama-Michael conjugate addition on various conjugated enones and ifs followed by a copper catalyzed cyclopropanation of the resulting enol ether. This cyclopropane fragments in situ to generate a cyclopentane with a [Beta]-keto ester. The scope of this reaction was probed on a variety of substrates containing enones with various substitution patterns as well as other potentially reactive functional groups. The second chapter describes the total synthesis of the natural product (--)-viridin, a furanosteroid. Viridin is the parent molecule for a class of natural products that covalently inhibit the function of phosphatidylinositol 3-kinase, a cell-signaling protein of interest in cancer and inflammation pathways. A key component of this convergent synthesis is an intramolecular Liebeskind coupling followed immediately by an intramolecular, asymmetric Heck reaction to couple the two halves together in an enantioselective fashion. The synthesis is 17 steps from commercial (longest linear) and yields material that is of >99% enantiomeric purity

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