亚硝基–烯反应的合成方法学及其在生物碱合成中的应用研究

复杂天然产物全合成往往由于其合成策略的创新性而广受关注，一些在合成化学发展史上备受推崇的明星分子一直是新策略和新方法发现的源泉。鉴于2-氮杂[3.3.1]壬烷环系（或称吗啡烷morphan）是许多复杂生物碱的核心骨架，围绕该结构的合成方法层出不穷。但是对于官能团密集的生物碱的全合成，现有的合成策略和方法依然不够高效。本项目的研究是基于前期亚硝基-烯反应快速构建2-氮杂[3.2.1]辛烷的合成方法，创新性地拓展应用于2-氮杂[3.3.1]壬烷环系的构建；并计划较为详细地研究其合成方法学，如6-endo/6-exo的反应模式，更好地理解该反应的机理；构建新颖结构的环系，设计应用于akuammiline 家族中代表性化合物strictamine 的全合成，并能从关键中间体出发，开展pincrine 和scholarisine A的合成研究。

Innovation in synthetic strategy is often the central theme during the total synthesis of complex natural products. Those hot molecules in organic synthesis are continuing sources for evolving novel strategy and method development. Due to 2-aza[3.3.1]nonane (also known as morphan) is the core structure in numerous complex alkaloids, many synthetic methods have been invented. However, for those functionally condensed alkaloids, the documented approaches are suffered for lower efficiency. The current proposal focuses on development of novel approach to access 2-aza[3.3.1]nonane (morphan) via a nitroso-ene cyclization, which was firstly introduced in the previous synthesis of alkaloid containing 2-aza[3.2.1]octane in this Principal Investigator’s laboratory. A set of new reaction modes, such as 6-endo or 6-exo cyclizations, will be investigated for better understanding the reaction mechanism. Moreover, this unprecedented strategy will be implemented into the efficient synthesis of strictamine, a challenging target in the akuammiline family. Similar structures like pincrine and scholarisine A are also merged for future synthesis.