DNA-Compatible ortho -Phthalaldehyde (OPA)-Mediated 2-Substituted Isoindole Core Formation and Applications

作者：Qigui Nie, Xianfu Fang, Changyang Liu, Gong Zhang, Xiaohong Fan, Yangfeng Li, Yizhou Li · 发表于：The Journal of Organic Chemistry · 年份：2022 · DOI：10.1021/acs.joc.1c02496 · 被引用次数：36 · 研究领域：Synthesis and pharmacology of benzodiazepine derivatives、Cancer therapeutics and mechanisms、Chemical Synthesis and Analysis

The incorporation of the isoindole core into the DNA-encoded chemical library is highly desirable for the great potential pharmacological characters exampled by molecules like lenalidomide. Herein, we reported a DNA-compatible protocol for the OPA-mediated transformation of amines into drug-like moieties represented by isoindolinone and thio-2-isoindole, respectively. The high conversion and wide substrate-scope property of our protocol render its feasibility in the manipulation of terminal amines on oligonucleotide conjugates, including "cap-and-catch" purification, sequential synthesis during DEL construction, and on-DNA macrocyclization.