中国科学院上海有机化学研究所李昂团队近日实现了Ambiguine P的简捷全合成。2025年5月20日出版的《美国化学会志》发表了这项成果。

Ambiguine P（5）是具有综合挑战性的hapalindole型天然产物的代表。受吲哚萜类化合物生物合成的启发，研究组开发了Cope/Prins/Friedel-Crafts级联，实现了从2,2-二甲基环庚酮到5的六步合成。与生物合成途径不同，该级联策略性地从带有七元环的三环吲哚啉衍生物开始，从而能够有效构建5的五环支架。在最后阶段，通过氯化和羟基化提高了氧化态。

附：英文原文

Title: Concise Total Synthesis of Ambiguine P

Author: Yifan Fei, Bo Fan, Zhigang Liu, Mengyu Ba, Zhongwen Cui, Peng Yang, Ang Li

Issue&Volume: May 20, 2025

Abstract: Ambiguine P (5) is a synthetically challenging representative of the hapalindole-type natural products. Inspired by the biosynthesis of this indole terpenoid family, we developed a Cope/Prins/Friedel–Crafts cascade, achieving a six-step synthesis of 5 from 2,2-dimethylcycloheptanone. Altered from the biosynthetic pathway, this cascade strategically commenced with a tricyclic indolenine derivative bearing a seven-membered ring, enabling efficient construction of the pentacyclic scaffold of 5. The oxidation state was elevated through chlorination and hydroxylation in the final stage.

DOI: 10.1021/jacs.5c00395

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c00395