Becker Michael H, Chua Peter, Downham Robert, Douglas Christopher J, Garg Neil K, Hiebert Sheldon, Jaroch Stefan, Matsuoka Richard T, Middleton Joy A, Ng Fay W, Overman Larry E
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
J Am Chem Soc. 2007 Oct 3;129(39):11987-2002. doi: 10.1021/ja074300t. Epub 2007 Sep 12.
This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (+)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4'-C3'-C7' stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late-stage installation of the tertiary amine-aldehyde proximity interaction.
本文描述了我们对复杂海洋生物碱沙林 A 进行合成研究的细节。我们构思了各种策略，遭遇了挫折，并开发了解决方案，最终实现了成功的对映选择性全合成。我们合成（+）-沙林 A 的路线有多个关键步骤，包括通过不对称迈克尔加成来构建 C4'-C3'-C7' 立体三联体，通过烯氧基硅烷 - N - 磺酰基亚胺离子环化来确定 C3 季碳立体中心并组装二氮杂三环十一烷核心，通过关环复分解反应构建 13 元环，通过分子内 Stille 偶联形成不饱和的 14 元大环，以及在后期引入叔胺 - 醛邻近相互作用。
