基于区域选择性分子内HECK反应的活性多环天然生物碱全合成研究

含吲哚、吡咯结构的多环生物碱是自然界中广泛存在的一类活性分子，由于结构独特，其全合成研究已经引起科学家们的极大兴趣。分子内HECK反应是构建多环天然产物骨架的最有效的途径之一，然而由于多个反应位点的存在，如何调控分子内HECK反应（包括C-H氧化HECK反应和经典HECK反应）的区域选择性已成为多环生物碱全合成的难点问题。课题组在前期研究中发现：1）利用弱导向基团的导向作用和强络合溶剂对弱导向基团的去导向作用可以控制吡咯C,2，C5-H分子内氧化HECK反应的区域选择性；2）利用底物结构不同可以调控吲哚C2， C7-位分子内经典HECK反应的区域选择性。本项目旨在此基础上，深入开展分子内HECK反应区域选择性调控研究，揭示吡咯、吲哚上分子内HECK反应的区域选择性调控机制，阐明其调控规律，进而利用本项目发展的分子内HECK反应区域选择性控制新策略，完成含吲哚、吡咯结构的天然生物碱的全合成。

As one of the most prevalent groups of naturally occurring chemical compounds, the total synthesis of polycyclic pyrrole and indole alkaloids has attracted much attention in the synthetic community due to the unique structural features and interesting bioactivities over the last few decades. Although intramolecular HECK reaction was recognized as one the most efficient methods to construct the polycyclic framework of natural alkaloids, how to control the regioselectivity of the intramolecular HECK reaction (including oxidative HECK and classical HECK reaction) still remains a big challenge for synthetic chemists due to the existence of multiple positions. We have previously developed solvent-controlled regioselective and switchable C2, C5-H alkenylation of 4-benzylpyrrole-3-carboxyaltes and substrate-controlled intramolecular HECK reaction of N-substituted indoles. This proposal is aimed to further investigate the modulation mechanism of these two methodologies and their synthetic applications to the total synthesis of the polycyclic pyrrole and indole alkaloids, such as natural alkaloids of Rhazinicine family, Hinckdentine A, Comasine、Erythraline，Lycoraline B, etc.