通过循环顺序重排实现喹啉类的可切换骨架编辑，这一成果由上海交通大学吴华团队经过不懈努力而取得。该研究于2025年4月7日发表于国际一流学术期刊《自然—化学》杂志上。

在这里，课题组人员报道了喹啉类化合物通过Br建立了喹啉N-氧化物、二烷基乙炔二羧酸盐和水的酸催化多组分反应，以模块化的方式生成含氮杂芳香化合物和线性化合物。具体来说，在一锅过程中，经过环化和顺序重排过程，喹啉N-氧化物很容易转化为独特的2-取代吲哚。然后经过酸促进裂解生成吲哚，碱促进开环生成2-肯苯胺，氧化环化生成异喹啉酮。喹啉类药物的催化不对称骨架编辑也得以实现，提供了具有四元立体中心的对映体富集的苯氮卓类药物，并证明了几种药物中喹啉核心的后期骨架修饰。

据介绍，通过可切换的骨架编辑在复杂分子中快速多样化核心环结构在药物发现过程中是有价值的。然而，尽管有可能最大限度地提高结构多样性和复杂性，但对偶氮芳烃框架进行化学差异性修饰的可控方法仍然具有挑战性。

附：英文原文

Title: Switchable skeletal editing of quinolines enabled by cyclizative sequential rearrangements

Author: Tian, Di, He, Yu-Ping, Yang, Lu-Sen, Li, Zhuo-Chen, Wu, Hua

Issue&Volume: 2025-04-07

Abstract: The rapid diversification of core ring structures in complex molecules through switchable skeletal editing is valuable in the drug discovery process. However, controllable methods for chemically divergent modifications of azaarene frameworks using common substrates are challenging, despite the potential to maximize structural diversity and complexity. Here we report the tunable skeletal editing of quinolines through Brnsted acid-catalysed multicomponent reactions of quinoline N-oxides, dialkyl acetylenedicarboxylates and water to generate nitrogen-containing heteroaromatic compounds together with linear compounds in a modular fashion. Specifically, in a one-pot procedure, after cyclization and sequential rearrangement processes, the quinoline N-oxides are easily converted into unique 2-substituted indolines. These then undergo acid-promoted fragmentation to give indoles, base-facilitated ring-opening to afford 2-alkenylanilines and oxidative cyclization to yield isoquinolinones. Catalytic asymmetric skeletal editing of quinolines is also realized, providing enantioenriched benzazepines bearing quaternary stereocentres, and late-stage skeletal modification of quinoline cores in several drugs is demonstrated.

DOI: 10.1038/s41557-025-01793-0

Source: https://www.nature.com/articles/s41557-025-01793-0