Guixian Zhao; Huihong Wang; Jie Luo; Xun He; Feng Xiong; Yangfeng Li; Gong Zhang; Yizhou Li
Org. Lett., 2023, 25(4), 665-670
https://doi.org/10.1021/acs.orglett.2c04293

Abstract

Annelated benzodiazepines are attractive drug-like scaffolds with a broad spectrum of biological activities. Incorporation of this heterocyclic core into DNA-encoded chemical libraries (DELs) via multicomponent assembly is highly demanded. Herein, we developed a DNA-compatible method to generate the tricyclic benzodiazepine scaffold via catalyst-free three-component condensation using a broad range of aldehyde, o-phenylenediamine, and diketone sources. With either aldehyde or o-phenylenediamine conjugated with DNA tags, functionalized 1,5-benzodiazepine scaffolds were efficiently forged, expanding the chemical space of the diazepine-centered drug-like DEL.