有机催化构筑手性吲哚螺环结构及其在合成中的应用研究

项目名称： 有机催化构筑手性吲哚螺环结构及其在合成中的应用研究

项目编号： No.21272150

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 吴小余

作者单位： 上海大学

项目金额： 80万元

中文摘要： 吲哚螺环结构广泛存在于许多马钱子属生物碱和钩藤属生物碱中，在过去数十年如何高效构建这类结构一直是个研究热点。以最近十来年发展起来的不对称有机小分子催化为基础，本项目旨在发展一些高效手性构建这类结构的方法。充分利用吲哚2-位和3-位的特殊反应活性，通过在底物或反应中间体的吲哚片断的2-位或者3-位引入卤素等策略实现螺环的构建；通过对反应条件进行摸索和优化，特别是对产生螺环手性中心的步骤进行优化，确认反应产物中各种非对映异构体的结构及在产物中的所占的比例，发展一些能高效合成天然产物生物碱关键中间体的方法学；待方法学研究取得一定结果之后，尝试将所发展的方法学用于若干具有吲哚螺环结构的生物碱的合成。预计本项目的研究工作的开展，将为高效构建手性吲哚螺环结构开辟一些新的途径。

中文关键词： 吲哚；生物碱；有机催化；串联反应；手性

英文摘要： Indole-based spiral scaffolds are widely found in strychnos and rhynchophylla alkaloids, and thus it is not surprising to see explosive interests and tremendous efforts in their construction over the past decades. The main objective of this proposal is to build up these spiral scaffolds via cascade reactions based on organocatalysis, which has witnessed remarkable progress in the past few years. For an indolyl substrate, a halogen atom would be introduced into 2- or 3- position of the indole moiety by modulating the reactivity of these positions, and the halogenated intermediate would play an important role in the formation of spiral chiral centers. The reaction conditions especially those involving formation of spiral centers would be carefully studied and optimized to increase the ratio of the desired diastereomer over the undesired. Once the cascade sequence has been successfully developed, the results will be applied in the total synthesis of alkaloids. The idea presented in this proposal is an integrated combination of organocatalysis and cascade reactions, and will be very useful in the synthesis of alkaloids with spiral subunits.

英文关键词： indole；alkaloid；organocatalysis；cacade reaction；chiral