经N-烯基硝酮高效构筑氮杂八元环方法研究及其在吲哚类生物碱合成中的应用

发展高效构筑氮杂八元环核心骨架生物碱的新策略和新方法是有机合成中非常具有挑战性的一个研究领域，而氮杂八元环骨架的高效构建对研究这类生物碱的开发与利用具有重要的作用。目前报道的构建这一骨架的反应大部分受限于复杂的多步合成、有限的底物类型和产率偏低。本项目拟研究N-烯基硝酮与亚甲基环丙烷高效构建氮杂八元环骨架的反应。反应经历N-烯基硝酮与亚甲基环丙烷环加成反应高区域选择性地生成环加成中间体；随后中间体经过Brandi-Gunara重排反应生成氮杂八元环骨架。本项目通过烯基高碘试剂发展系列N-烯基硝酮的简易合成方法，并研究N-烯基硝酮高效构建氮杂八元环骨架的普适性，同时将所发展的这类方法学应用到含有吲哚并氮杂八元环生物碱核心骨架的合成中，对天然产物Lundurine 类似骨架进行修饰，为合成该类生物碱提供简单高效的方法，为对其进行更深入研究与开发奠定基础。

To develop novel strategies and methods for efficiently building azacyclooctane skeleton in alkaloids is a challenge research area in organic synthesis. It will play an important role on explorations of these alkaloids. However, methods reported for this research area require multi-step synthesis, special substrates or lower yields. This proposal focuses on efficiently developing a novel procedure for preparation of azacyclooctane skeleton via cycloaddition reaction of new N-vinyl nitrones and methylenecyclopropanes. A protocol is presented that allow for the regio-selective generation of cycloaddition products by the reaction of N-vinyl nitrones and methylenecyclopropanes. The highly reactive cycloaddition intermediates will go through Brandi-Gunara rearrangement to form azacyclooctane skeleton. A new simple method for preparation of N-vinyl nitrones will be developed from hypervalent vinyl iodonium salts and the scope of the azacyclooctane skeleton will be investigated. Furthermore, this method will be applied to synthesis of alkaloids containing indole and azacyclooctane skeleton as well as modification. It will provide not only a simple and efficient way to build these types of alkaloids, but also the foundation for further research and development on these alkaloids.