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

• DOI: 10.1021/acs.joc.1c02496
• Publication Date: 2022-01-25T16:56:34Z
• Authors: Qigui Nie; Xianfu Fang; Changyang Liu; Gong Zhang; Xiaohong Fan; Yangfeng Li; Yizhou Li
• Keywords: encoded chemical library; Chemical Sciences not elsewhere classified; like moieties represented; including “ cap; Biophysics; highly desirable; Isoindoles; Biochemistry; 01 natural sciences; Space Science; mediated transformation; del construction; Genetics; Amines; ortho </; Molecular Biology; oligonucleotide conjugates; Cancer; Pharmacology; scope property; >- phthalaldehyde; high conversion; wide substrate; DNA; 540; 0104 chemical sciences; molecules like lenalidomide; sequential synthesis; catch ” purification; protocol render; o-Phthalaldehyde; Developmental Biology

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.