Qigui Nie; Xianfu Fang; Changyang Liu; Gong Zhang; Xiaohong Fan; Yangfeng Li; Yizhou Li
J. Org. Chem., 2022, 87(5), 2551-2558
https://doi.org/10.1021/acs.joc.1c02496

Abstract

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.