DNA-Compatible <i>ortho</i>-Phthalaldehyde (OPA)-Mediated 2-Substituted Isoindole Core Formation and Applications
Qigui Nie, Xianfu Fang, Changyang Liu, Gong Zhang, Xiaohong Fan, Yangfeng Li, Yizhou Li
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.
Topics & Concepts
IsoindoleDNAChemistryCombinatorial chemistryOligonucleotideStereochemistryBiochemistrySynthesis and pharmacology of benzodiazepine derivativesCancer therapeutics and mechanismsChemical Synthesis and Analysis