Department of Chemistry , University of California , Berkeley , California 94720 , United States.
J Am Chem Soc. 2019 May 29;141(21):8431-8435. doi: 10.1021/jacs.9b03576. Epub 2019 May 16.
The first total synthesis of the complex hexacylic Daphniphyllum alkaloid (-)-daphlongamine H has been accomplished. Key to the success of the strategy are a complexity-building Mannich reaction, efficient cyclizations, and a highly diastereoselective hydrogenation to assemble multigram quantities of the tricyclic core bearing four contiguous stereocenters. Following construction of the hydro-indene substructure by means of a Pauson-Khand reaction, endgame redox manipulations delivered the natural product. Importantly, the synthetic studies have also given access to (-)-isodaphlongamine H and led to a revision of the reported structure of deoxyisocalyciphylline B.
复杂的六环 Daphniphyllum 生物碱 (-)-daphlongamine H 的首次全合成已经完成。该策略的关键是一个复杂的 Mannich 反应、高效的环化反应和高度非对映选择性的氢化反应，可组装大量含有四个连续立体中心的三环核心。通过 Pauson-Khand 反应构建了氢化茚亚结构后，最终的氧化还原操作得到了天然产物。重要的是，合成研究还使我们获得了 (-)-异 daphlongamine H，并对报道的 deoxyisocalyciphylline B 的结构进行了修正。
