1-氮杂螺环结构广泛存在于多环生物碱中。我们前期的研究工作，已发展了两种基于酰胺N-alpha位碳自由基构造氮杂季碳的方法。本项目计划在此基础上，围绕1-氮杂螺环的构造，研究一氯二茂钛催化的自由基串联反应方法；进而，研究含1-氮杂螺环结构的复杂多环体系的构建方法；与此同时，设计全新的合成策略，开展舞蛙毒素Histrionicotoxin 291A（1），三环海洋生物碱 Polycitorol A（2），石松生物碱Lycospidine A（3）和虎皮楠生物碱Calyciphylline F（4）的全合成研究。这些化合物中，关于2的全合成只有一篇报道；1，3和4尚未见有全合成报道。该项目研究将能进一步探索一氯二茂钛催化的酰胺N-alpha位碳自由基反应的机理；并提供一种灵活、实用，基于自由基串联反应构建1-氮杂螺环的新方法；为具有该特征结构的系列生物碱的全合成提供新的方法与策略。

1-Azaspirocyclics can be frequently observed in many polycyclic alkaloids. A considerable number of synthetic methods have been reported to establish the peculiar structure. However, some limitations also have existed, especially in the radical approaches. Previously, based on the alpha-acylaminoalkyl radicals, two methods have been developed to construct aza-quaternary carbons in our group. On the basis of these, in this project, some novel titanocene-catalyzed cascade radical methods will be developed for constructions of 1-azaspiro ring system, and then, for complex polycyclic systems containing this motif. Furthermore, to study the mechanism and stereoselectivity of these cascade radical methods, some novel synthetic routes will be established for total synthesis of a histrionicotoxin 291A (HTX-291A) (1)，a tricyclic marine alkaloid polycitorol A (2)，a lycopodium alkaloid lycospidine A (3) and a daphniphyllum alkaloid calyciphylline F (4). Among them, only one route of total synthsis of polycitorol A has been reported, the others never have been synthesized. This project will give a further insight into the mechanism of titanocene monochloride-catalyzed reactions of alpha-acylaminoalkyl radicals, and provide a flexible, practical and cascade radical reaction-based methodology to construct the 1-azaspiro ring system, which will establish some efficient synthetic routes, involving novel strategies for the total synthesis of 1-azaspirocyclic containing alkaloids .