Enantioselective total synthesis of altohyrtin C (spongistatin 2)

被引:161
作者
Evans, DA [1 ]
Trotter, BW [1 ]
Coleman, PJ [1 ]
Côté, B [1 ]
Dias, LC [1 ]
Rajapakse, HA [1 ]
Tyler, AN [1 ]
机构
[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
关键词
asymmetric synthesis; antitumour compounds; marine metabolites; aldol reactions;
D O I
10.1016/S0040-4020(99)00438-X
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The first total synthesis of a spongipyran macrolide, altohyrtin C, is described. The convergent synthesis strategy relies on a regioselective macrolactonization, a stereoselective Wittig coupling of the two major synthetic fragments, a complex anti aldol reaction to join the C-1-C-15 and C-16-C-28 spiroketal regions, and an anomeric sulfone acylation to join the C-29-C-37 and C-38-C-43 pyran regions. The incorporation of the C-44-C-51 sidechain in the final stages of the synthesis establishes a viable route for the construction of variants in this pharmacologically important region. Methodological developments en route to the total synthesis include a 1,5 anti-selective methyl ketone aldol reaction and a diastereoselective approach to Lewis acid mediated beta-C-glycosidation. Completion of the synthesis has confirmed the stereochemical assignments proposed in the altohyrtin series and has established the identity of the altohyrtin and spongistatin marine macrolides. (C) 1999 Elsevier Science Ltd. Ail rights reserved.
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页码:8671 / 8726
页数:56
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