State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (China).
Angew Chem Int Ed Engl. 2015 May 18;54(21):6255-9. doi: 10.1002/anie.201411338. Epub 2015 Apr 2.
The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)-lycoramine (2) have been achieved by using a conceptually new strategy featuring two metal-catalyzed reactions as the key steps. A new method for the construction of 3,4-fused benzofurans has been developed through a palladium-catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric synthesis of 1 and 2, a Sc(III)/N,N'-dioxide complex was used to catalyze the enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center.
通过采用两个金属催化反应作为关键步骤的全新策略，实现了 (-)-加兰他敏 (1) 和 (-)-石蒜碱 (2) 的催化不对称全合成。通过钯催化的分子内 Larock 环化反应，开发了一种构建 3,4-稠合苯并呋喃的新方法，该方法成功地应用于 1 和 2 的 ABD 三环骨架的构建。为了实现 1 和 2 的不对称合成，使用 Sc(III)/N，N'-二氧杂环戊烷配合物催化 3-烷基取代苯并呋喃酮与甲基乙烯基酮的对映选择性共轭加成，构建手性季碳中心。
