海洋天然药物学(推荐2).ppt

* Projects: the neurologically active marine natural product gymnodimine; the antimicrobial marine natural product gambieric acid; and the potent anticancer agents which also happen to be marine natural products eleutherobin and veiutamine. New synthesis strategies: tandem free-radical reactions, new carbonyl-olefin metathesis transformations, and stereoselective cycloaddition reactions. University of Arizona, Rainer’s Group Rainier, J. D.; Allwein, S. P.; Cox, J. M. C-Glycosides to Fused Polyethers. A Formal Synthesis of (±)-Hemibrevetoxin B, J. Org. Chem. 2001, 66, 1380. University of Arizona, Synthesis Eleutherobin, from a marine soft coral of the Eleutherobia species, was first reported in 1995 by the group of Fenical1. It was immediately shown to possess activity as an inhibitor of microtubule depolymerisation with a mean cytotoxicity that was greater than that exhibited by taxol or the recently described epothilones 2. It has already been the subject of two total syntheses 3,4 , but these syntheses were linear rather than convergent. Our approach is convergent5 and proceeds according to the analysis shown below. 1. T, Lindel, P. R. Jensen, W. Fenical, B. H. Long, A. M. Casazza, J. Carboni, and C. R. Fairchild, J Am. Chem. Soc., 1997, 119, 8744. 2. G. Hofle, N. Bedorf, H. Steinmetz, D. Schomberg, K. Gerth, and H. Reichenbach. Angew. Chem., 1996, 35, 1567. 3. K. C. Nicolaou, F. van Delft, T. Oshima, D. Vourloumis, J. Xu, S. Hoskawa, J. Pfefferkorn,, S. Kim, and T. Li. Angew. Chem., 1997, 36, 2520. 4. X.-T. Chen, C. E. Gutteridge, S. K. Bhattacharya, B. Zhou, T. R. R. Pettus, T. R. Hascall, and S. J. Danishefsky. Angew. Chem., 1998 , 37, 185 and 789. 5. A. Baron, V. Caprio and J. Mann. Tet. Lett., 1999, 40 , 9321.  A convergent approach to eleutherobin : a marine natural product with taxol-like activity Eleutherobin synthesis Shark Cartilage and Cancer: The Exciting Possibility of a Cancer-free State with a Natural Product It is believed that all of