六种依波加明类单萜吲哚生物碱的不对称集群合成

依波加明类生物碱具有新颖多变的骨架结构和较好的生物活性，一部分已经发展成药，是有机化学和药物化学研究的重点目标。本项目根据依波加明类生物碱核心骨架的共性，拟采用自己课题组发展的可见光催化的羰基烷基化反应以及手性磷酸催化的对映选择性和非对映选择性的串联异构化/螺环化/去芳构化反应作为关键步构建依波加明类生物碱的螺环吲哚啉核心骨架，通过钐介导的还原环化反应实现五环骨架的构建，以集群合成的方法和特异性的合成路线进行6种依波加明类生物碱的不对称全合成。项目拟采用的合成策略简洁新颖，方法高效，可快速合成依波加明类生物碱，具有很高的可行性。项目设计并合成四种类型的衍生物，进行抗肿瘤活性研究，为该类生物碱及其衍生物的制备提供有效的合成方法，为药物研究和开发提供基础。

The Iboga indole alkaloids are featured with intricate skeletons and promising biological activities. Many of the iboga alkaloids have been utilized as medicines. These alkaloids are the highlighted molecules both in organic chemistry and medicinal chemistry. This project will construct the core skeleton of Iboga indole alkaloids by a photochemical α-carboxyalkylation, and a diastereoselective and enantioselective tandem enamine isomerization/spirocyclization/dearomatization reaction of the tryptamine-derived indolyl dihydropyridine under the catalysis of the chiral phosphoric acid developed by our group. A Sm-mediated reductive cyclization will be applied to synthesis the pentacyclic skeleton of Iboga indole alkaloids. The collective synthetic strategy and specific synthetic method were applied to synthesis of six Iboga indole alkaloids, including (+)-pandoline, (+)-pandine, (+)-pseudotabersonine, vidolincine, iboxyphyllie, and ibophyllidine. The proposed synthetic protocol and methodology are featured with novelties and high efficiencies, which have good feasibility. It will provide efficiently synthetic strategies for pandoline-related alkaloids. Furthermore, we will synthesize four-type derivatives to identify their potential antitumor activities and their structure-activity relationship. It will afford practically synthetic strategies for Iboga indole derivatives, and benefit the potential medicinal studies and development.