Multicomponent DNA-Compatible Synthesis of an Annelated Benzodiazepine Scaffold for Focused Chemical Libraries
Guixian Zhao, Huihong Wang, Jie Luo, Xun He, Feng Xiong, Yangfeng Li, Yangfeng Li, Gong Zhang, Yizhou Li, Yizhou Li
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.