Akuammiline生物碱的全合成研究

Akuammiline alkaloids are featured with universal biological activities. These natural products are also characterized with complex caged structure, as well as multi chiral centers. Moreover, the akuammiline alkaloids are divided into several subtypes according to the different bond connectivity. Owing to the above conspicuous properties, akuammiline alkaloids are highlighted as synthetic targets but also are full of challenge. However, most of the synthetic efforts are focused on the limited molecules. Other akuammiline alkaloids, such as echitamine, which was isolated and reported for more than 140 years, no synthetic methods were documented up to today. This project will focus on the enantioselective synthesis of four akuammiline alkaloids which are belonged to two different subtypes. Divergent strategy will be adopted on basis of the biogenetic relationship and structural characteristic. A continuous three-time visible light-induced photoreaction will be involved in the total synthesis as key steps to enantioselectively generate the five rings. Moreover, the two subtypes will be able to convert each other by the rings recombination. The strategy with continuous visible light-induced photoreactions as key steps will offer an alternative pathway to natural products.

Akuammiline生物碱是一类具有广泛生物活性的天然产物，由于该类分子具有多手性的笼状复杂结构，且存在不同类型的连接方式，是有机化学中的热点也是难点。目前对该类生物碱的全合成研究主要集中在有限的几个分子，但对一些结构更复杂的分子则依旧缺乏合适的合成方法，如echitamine分子已分离报道140多年，但到目前为止尚未有成功的合成报道。本项目将根据akuammiline生物碱在生源上的关联性和结构特征，采用多样化合成策略，通过关键共同中间体的设计，对两种类型四个不同结构的akuammiline生物碱进行手性全合成研究。在研究中将采用连续三次可见光引发的反应为关键步骤，非对映选择性地构建akuammiline生物碱的五个环系。通过环系重组，实现两种不同类型生物碱的相互转化。本项目采用了全新的连续可见光引发反应构建天然产物关键结构的合成策略，拓宽了天然产物合成化学的新思路。

本项目以若干akuammiline型生物碱为研究对象，针对该类生物碱存在N4-C2和N4-C3连接两种不同的结构，以及具有挑战性的多个连续的手性中心，拟以课题组前期发展多种不对称可见光反应为基础，通过光反应在反应机理和成键方式上与常规反应存在的差异性，设计akuammiline型生物碱关键骨架的全新构建方法，突破现有全合成中的一些难点，以期为这些多环生物碱的集群合成提供新思路和新方法。