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

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.

Automated summary

This study reported a new DNA-compatible protocol for the transformation of amines into drug-like moieties, expanding the application of DNA-encoded chemical libraries.