德国马克斯·普朗克煤炭研究所Tobias Ritter团队研究了用于DNA编码库的富电子芳烃在DNA上的C-H功能化。该项研究成果发表在2025年6月16日出版的《自然-化学》杂志上。

DNA编码文库（DEL）可用于制药行业的热门发现。尽管可以通过DEL获得大量单独编码的分子，但它们的结构多样性是有限的，因为很少有转化是良性的，并且具有足够的化学选择性，可以在水性环境中存在DNA的情况下应用。特别是，目前DEL合成中还没有理想地适合通过后期官能化增加结构多样性的C-H官能化化学。 

研究组提出了DNA上富电子芳烃的一般C-H官能化。开发一种硒氧化物试剂是实现芳基硒鎓盐在水介质中区域和化学选择性形成的关键。芳基硒鎓盐的引入为DNA偶联物提供了一个多功能的关键，通过各种后续反应，包括过渡金属介导的光化学转化形成C-C、C-I和C-S键，可以获得多种类似物。

附：英文原文

Title: On-DNA C–H functionalization of electron-rich arenes for DNA-encoded libraries

Author: de Pedro Beato, Eduardo, Torkowski, Luca, Hartmann, Philipp, Vogelsang, Lara, Dietz, Karl-Josef, Ritter, Tobias

Issue&Volume: 2025-06-16

Abstract: DNA-encoded libraries (DELs) are useful for hit discovery in the pharmaceutical industry. Although a large number of individually coded molecules are accessible through DELs, their structural diversity is limited because few transformations are benign and chemoselective enough to be applied in the presence of DNA in aqueous environments. In particular, C–H functionalization chemistry that could be ideally suited to increase structural diversity through late-stage functionalization is currently absent from DEL synthesis. Here we present a general C–H functionalization of electron-rich arenes on DNA. The development of a selenoxide reagent is key to achieving the regio- and chemoselective formation of arylselenonium salts in aqueous media. The introduction of arylselenonium salts offers a versatile linchpin on DNA conjugates, which gives access to a multitude of analogues through diverse subsequent reactions, including transition-metal-mediated and photochemical transformations for the formation of C–C, C–I and C–S bonds.

DOI: 10.1038/s41557-025-01844-6

Source: https://www.nature.com/articles/s41557-025-01844-6