Development of On‐DNA Cyclic Imide Synthesis for DNA Encoded Library Construction

Abstract Here, we describe a novel method for the on‐DNA synthesis of cyclic imides, an important class of molecules that includes several well‐known medications. Significantly, the new method enabled on‐DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis‐carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off‐DNA and on‐DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.