DNA-encoded chemical library (DEL) has emerged as a cost effective platform for hit generation. The chemical and structural diversity of the small molecules displayed by the DEL is critical to successful discovery of novel drug-like chemical matters. Thus, the availability of efficient synthetic methods that enable facile derivatization and are compatible with structurally diverse building blocks is key to the preparation of diverse DELs. Amide bond formation is one of the most commonly used reactions for DEL synthesis, due to the easy access to large and diverse sets of carboxylic acids and amines. While the majority of the reported acylation involve reactions between DNA-conjugated amines and carboxylic acids, there are few examples of acylation between DNA-conjugated carboxylic acids and amines, presumably due to limited methods that activate acids in water. In addition, the existing methods are limited in substrate scope and are not effective with sterically hindered carboxylic acids. Herein, we report a facile and versatile amide coupling between DNA-conjugated carboxylic acids and amines. This reaction offers a broad substrate scope in terms of both acids and amines. DNA-conjugated sterically hindered carboxylic acids efficiently couple with a wide variety of amines. The mechanism of activation of acid in water will also be discussed.

Efficient acylation of DNA-conjugated carboxylic acids with amines in aqueous media

254th National Meeting (2017)

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