Fischer吲哚合成/[3,3]-Claisen重排串联反应及其在吲哚生物碱合成中的应用

Lundurine alkaloid is a family of indole alkaloids with novel structure and important biological activities. Efficient total synthesis of lundurine alkaloids remains a big challenge due to its complex structure. Based on the unprecedented structure of grandilodine-type alkaloids, this project focuses on developing tandem Fischer indolization/[3.3]-Claisen rearrangement to build-up 2,2-disubstituted indolin-3-one framework from easily available phenyl hydrazine and alloxyl ketone. For the subsequent synthesis of grandilodine-type alkaloids, asymmetric vinylogous Michael addition followed by RCM reaction would produce spiro-ketone, which could be subjected to the tandem indolization/[3.3]-Claisen rearrangement reaction conditions to afford the key synthetic intermediate. From this common intermediate, collective synthesis of grandilodine-type alkaloids could be achieved.

Lundurine类吲哚生物碱是一类结构新颖、具有重要生理活性的吲哚生物碱。由于结构比较复杂，这类天然产物的高效合成仍是一项具有挑战意义的课题。本项目针对grandilodine吲哚生物碱独特的结构，发展苯肼和烯丙氧基酮的Fischer吲哚合成/[3,3]-Claisen重排串联反应，一步构建2,2-双取代的吲哚啉酮骨架。接下来对grandilodine类吲哚生物碱的合成，则可以通过不对称插烯Michael加成、RCM反应为关键反应合成串联反应前体。然后通过串联反应构建双螺环中间体。从此中间体出发，完成grandilodine类吲哚生物碱的集体合成。