近日，瑞士苏黎世联邦理工学院Bill Morandi团队揭示了碳-氮原子交换可以从类药物吲哚中直接获得苯并咪唑。2025年9月2日出版的《自然-化学》杂志发表了这项成果。

在原子水平上选择性编辑有机分子的能力有可能简化制药和农用化学工业中铅的发现和优化。虽然最近已经报道了许多原子插入和删除反应，但单原子交换的例子仍然很少，因为在同一原子周围编排选择性切割和形成多个化学键颇具挑战。

研究组报道了一种在N-烷基吲哚中进行碳-氮原子交换的方法，使吲哚直接转化为相应的苯并咪唑。该反应利用吲哚支架的固有反应活性进行初始氧化裂解步骤，随后是氧化酰胺化，霍夫曼型重排和环化。这个复杂的步骤序列是由市售苯基吡啶（III）二乙酸酯和氨基甲酸铵作为氮原子的简单组合介导的。该反应可耐受多种官能团，15种药物样分子的相互转化证明了这一点，这意味着它可立即适用于广泛的发现计划。

附：英文原文

Title: Carbon-to-nitrogen atom swap enables direct access to benzimidazoles from drug-like indoles

Author: Paschke, Ann-Sophie K., Brgger, Yannick, Botlik, Bence B., Staudinger, Erich, Green, Ori, Morandi, Bill

Issue&Volume: 2025-09-02

Abstract: The ability to selectively edit organic molecules at the atomic level has the potential to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. While numerous atom insertion and deletion reactions have recently been reported, examples of single atom swaps remain scarce due to the challenge of orchestrating the selective cleavage and formation of multiple chemical bonds around the same atom. Here we report a method for the carbon-to-nitrogen atom swap in N-alkyl indoles, allowing the direct conversion of indoles to the corresponding benzimidazoles. The reaction leverages the innate reactivity of the indole scaffold to engage in an initial oxidative cleavage step, followed by oxidative amidation, Hofmann-type rearrangement and cyclization. This complex sequence of steps is mediated by the simple combination of commercially available phenyliodine(III) diacetate and ammonium carbamate as the nitrogen atom source. The reaction tolerates a wide range of functional groups, which is demonstrated by the interconversion of 15 drug-like molecules, implying its immediate applicability across a wide range of discovery programmes.

DOI: 10.1038/s41557-025-01904-x

Source: https://www.nature.com/articles/s41557-025-01904-x