Enantioselective Total Synthesis and Structural Assignment of Callyspongiolide
Abstract
Callyspongiolide is a marine natural product which displays very potent antiproliferative properties towards human cancer cells in the low nM range. The mechanism of action is not yet known, but initial studies have indicated that the mechanism of action proceeds in a caspase-independent fashion. Ambiguity in the absolute structure of callyspongiolide and diminished supply necessitate chemical synthesis to further probe the full medicinal potential. We have prepared four stereoisomers corresponding to the structure of the proposed natural product. Our synthetic strategy is convergent and assembles the molecule in high enantio-, diastereo-, and regioselectivity. Notable reactions are and enantioselective CBS reduction of a tert-alkyl ketone, Yonemitsu’s modification of the Yamaguchi macrolactonization to cyclize an alkynyl seco acid, and a highly trans-selective, modified Julia olefination to forge the hindered C10–C 11 olefin. Comparison of our synthetic stereoisomers with reported spectral and biological data leads to an unambiguous structural assignment of the natural product.
Degree
Ph.D.
Advisors
Ghosh, Purdue University.
Subject Area
Organic chemistry
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