生物活性天然产物是药物候选结构和先导结构的重要来源。单萜吲哚生物碱是一类具有多种重要生物活性的天然产物，其化学空间广阔，成药性较高。本项目拟将炔胺串联[3+2]环加成用于若干单萜吲哚生物碱的不对称全合成。具体拟从以下两个方面开展工作：1）通过单一手性中心或环构型控制的选择性[3+2]环加成构建吲哚螺环缩醛胺骨架，再进一步转化为吲哚并二氮杂[3.3.1]桥环体系，最后经分子间Michael-Henry、自由基脱硝基实现(-)-Alsmaphorazine D的全合成。2）通过炔胺串联[3+2]环加成同时构建相邻季碳中心的策略，实现吲哚螺环缩醛胺核心骨架的合成，再构建δ-吲哚内酰胺，最后经Michael-Henry或aldol等转化实现一系列Aspidosperma型生物碱的不对称全合成。本项目在设计理念上将炔烃串联环加成和复杂天然产物的不对称全合成相结合，是对炔烃高效转化的创新应用。

Bioactive natural products are an important resource of drug candidates and lead compounds. Monoterpene indole alkaloids, a class of natural products with a range of important bioactivities, have a large chemical space and high druggability. The project is intended to realize asymmetric total synthesis of several monoterpene indole alkaloids through ynamine-mediated cascade [3+2] cycloaddition reaction. It is consisted of the following two aspects: 1) Using single chiral center or ring configuration to achieve a selective [3+2] cycloaddition, affording an indoline spiroaminal skeleton. The aminal skeleton is then advanced to a indole fused diazabicyclo[3.3.1] ring system, which finally lead to the (-)-Alsmaphorazine D through an intermolecular Michael-Henry and radical denitriation sequence. 2) An ynamine-mediated cascade [3+2] cycloaddition reaction is used to simultaneously construct the vicinal quaternary centers within an indoline spiroaminal skeleton, which followed by amidation to give a δ-lactamindole. After Michael-Henry or aldol etc. transformations, a series of Aspidosperma alkaloids could be accomplished in asymmetric manner. With respect to principle of design, this project combines the alkyne-mediated cascade reaction and asymmetric total synthesis of complex natural product, which represents an insightful and inspirational application of high-efficiency transformation of alkyne.