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Application of a titanium(III)-mediated coupling reaction toward the total synthesis of 7,11-epi-thyrsiferol and its pharmacological properties

Posted on:2006-09-10Degree:Ph.DType:Thesis
University:University of California, Santa BarbaraCandidate:Nishiguchi, Gisele AkemiFull Text:PDF
GTID:2451390005997205Subject:Chemistry
Abstract/Summary:
Thyrsiferol is a marine natural product known to display cytotoxic activity against cancer cell lines. The total synthesis of a novel analogue of thyrsiferol (7,11-epi-thyrsiferol, 3-73) is described, it featuring a titaniumIII-mediated coupling reaction. The regioselective opening of epoxide 3-57 and stereoselective formation of compound 3-56 using Cp2TiCl constitute the key transformations for the successful completion of 3-73. The total synthesis of 7,11- epi-thyrsiferol proceeded in 32 steps with 17 steps for the longest linear sequence. Efforts toward the total synthesis of the natural product thyrsiferol are also discussed.; Preliminary pharmacological studies indicated the novel analogue to inhibit cell division in the sea urchin assay at 11 muM concentration. In addition, the compound displayed a synergistic behavior with colchicine and it appears to be a substrate of multidrug resistance protein1 (MRP1).
Keywords/Search Tags:Total synthesis
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