SYNTHESIS OF THAPSIGARGIN ANALOGS

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The proposed research explores a synthetic strategy which will provide access to analogs of the tumor promoter thapsigargin (1). New adaptations of two metal-mediated synthetic methodologies will be examined. First, the synthesis of cycloheptene template 10 will extend available protocols for the selective functionalization of the known chiral allylmolybdenum complex 2. Second, palladium-catalyzed cycloisomerization of enyne 10 will be investigated as a means for forming a highly substituted bicyclo[5.3.0]decane system. Functional group manipulation of the resulting product will be pursued to provide tricyclic compound 21. The specific goals for the postdoctoral appointment are the acquisition of this synthetic target, as well as the validation of the methods mentioned above. However, the enantiomerically enriched target 21 represents a potentially general precursor for the preparation of analogs of thapsigargin and other guaiane natural products.