虎皮楠生物碱Daphniyunnine C 的全合成

Daphniphyllum is a genus of flowering plants, which has been used as Chinese traditional medicine for long time. Daphniyunnines C (longeracinphyllins A), as a Daphniphyllum alkaloid, was isolated by Yue et al, and Hao et al from the stems and leaves of Daphniphyllum yunnanense， and the leaves of daphniphyllum longeracemosum respectively. The structure of daphniyunnines C was elucidated on the basis of its NMR spectra and single-crystal X-ray diffraction determination. Different from normal Daphniphyllum alkaloids, daphniyunnines C features a new C-21-fused -hexacyclic ring system, including 8 stereocenters, two of which are quaternary carbons. Such special and complex skeleton drew extensive attention from organic chemists, however, up to date, there is no report on the total synthesis of this alkaloid.. .Based on the background, this proposal is focused on the asymmetric total synthesis of daphniyunnines C with small molecule catalyzed 1, 2-migration rearrangement reaction as the key step. In expectation, it does not only provide a new synthetic route for the total synthsis of its natural analogues and derivatives, but also is of great importance to divergent synthesis, bioactivities and structure-activity relationship studies of Daphniphyllum alkaloids, as well as to the development of Chinese traditional medicine.

虎皮楠是东南亚特有的药用植物属,作为传统中药,具有清热解毒、活血散瘀等功效。Daphniyunnines C是从我国虎皮楠属植物滇南桂和长序虎皮楠植物中分离得到的生物碱，由于具有高度密集的[6, 5, 6, 7, 5, 5]六环稠和骨架和8 个手性中心（其中两个为相邻的全碳季碳），结构复杂，所以分离至今仍未见全合成工作面世。本申请项目将以有机小分子催化的不对称1, 2-重排反应为关键步骤，设计完成Daphniyunnines C的首次不对称全合成。拟通过该项目的实施发展一条系列类似物不对称合成的新路线，为该生物碱的类天然产物多样性合成、生物活性及构效关系研究提供重要的基础，对推动我国传统中医药的现代化研究也具有重要的现实意义。

本项目基本按照项目申请书中的内容进行实施，主要开展了daphniyunnines C全合成及相关合成方法学的研究工作。期间，成功实现了daphniyunnines C分子四环骨架的构建，及(+)-alopecuridine, (+)-sieboldine A, (−)-lycojapodine A，(-)-8-deoxyserratinine, (-)-lycojaponicumins C, (+)-fawcettidine, (+)-fawcettimine等10余个分子的合成工作。同时，针对这些分子中关键骨架的构建发展了7类合成方法，为相应分子骨架的构建提供了新的合成方法。基本按计划完成了预定的任务，期间，发表SCI论文25篇，提交发明专利申请3项；培养硕士研究生7名（2015年毕业1名）；参加学术会议8次，并做邀请报告1次。