An Iminium Ion Cascade Annulation Strategy for the Synthesis of Akuammiline Alkaloid Pentacyclic Core Structures

The akuammiline alkaloids are a family of indole monoterpene natural products known for their polycyclic cage-like structures. An iminium ion cascade annulation approach was developed, simultaneously synthesizing both the C and D rings of these natural products by annulation onto a protected indole ring. This reaction allowed the synthesis of a key tetracyclic intermediate toward these natural products. This tetracycle was used for the synthesis of the pentacyclic methano­quinolizidine core present in such alkaloids as akuammiline and strictamine as well as the pentacyclic furoindoline core found in pseudo­akuammigine.

鸭山生物碱类（akuammiline alkaloids）是一类吲哚单萜类天然产物，以其多环笼状结构而闻名。研究人员开发了一种亚胺离子级联环化策略，通过在带有保护基的吲哚环上进行环化反应，同时构建该类天然产物的C环与D环。该反应可合成针对这类天然产物的关键四环中间体。上述四环中间体被用于合成两类五环核心结构：一类是存在于鸭山碱（akuammiline）与strictamine中的五环甲撑喹嗪核心（methanoquinolizidine core），另一类是存在于pseudoakuammigine中的五环呋喃并吲哚啉核心（furoindoline core）。