An Enantioselective Synthesis of FR182877 Provides a Chemical Rationalization of Its Structure and Affords Multigram Quantities of Its Direct Precursor
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- 作者：Christopher D. Vanderwal ; David A. Vosburg ; Sven Weiler ; and Erik J. Sorensen
- 刊名：Journal of the American Chemical Society
- 出版年：2003
- 出版时间：May 7, 2003
- 年：2003
- 卷：125
- 期：18
- 页码：5393 - 5407
- 全文大小：339K
- 年卷期：v.125,no.18(May 7, 2003)
- ISSN：1520-5126
文摘
The evolution of a strategy culminating in an efficient, enantioselective synthesis of the potentmicrotubule-stabilizing agent FR182877 is described. Guided by a proposed biogenesis of this complexnatural product, a solution emerged that involved the first reported example of a double transannular Diels-Alder reaction to fashion the key elements of its hexacyclic structure. This pivotal transformation createsa complex pentacycle from a 19-membered macrocyclic pentaene, forming seven new stereogenic centersin a fully diastereocontrolled fashion. The efficiency of the approach ultimately enabled the preparation ofmultigram quantities of the direct precursor of FR182877 for conversion to the relatively unstable naturalproduct when required. The reactivity of the strained, bridgehead olefin of this secondary metabolite withbiologically relevant nucleophiles is also described.