虎皮楠生物碱(Daphniphyllum alkaloid)是一大类从虎皮楠科植物中分离的具有化学、生物和生物合成等多方面研究意义的天然产物。李昂等发展了一条19步的合成路线，从4个结构简单的片段出发，反应完成了daphenylline的首次不对称全合成(Nature Chemistry 2013,5,679-684)。该合成主要的碳-碳键形成反应包括：金(I)催化的6-exo-dig炔烃环化反应以构建[3.3.1]桥环体系、分子内Michael加成反应以构建吡咯烷结构、光引发的烯烃异构化/6π电环化串联反应和随后的氧化芳构化反应以构建四取代苯环结构、自由基环化反应以构建七元环结构。这一工作将促进下一步的活性—靶点—机制的研究工作。%The Daphniphyllum alkaloids are a large class of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They display a remarkable range of biological activities, including anticancer, antioxidant, and vasorelaxation properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the predominately aliphatic Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on a sterically compact hexacyclic scaffold. Herein, we describe the first total synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction were exploited to construct the bridged 6,6, 5-tricyclic motif of the natural product at an early stage, and the aromatic moiety was forged through a photoinduced olefin isomerization/6p-electrocyclization cascade followed by an oxidative aromatization process.
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