Yurong Shen; Guanyu Yang; Wei Huang; Alex Shaginian; Qian Lin; Jinqiao Wan; Jin Li; Yun Deng; Guansai Liu
Org. Lett., 2022, 24(14), 2650-2654
https://doi.org/10.1021/acs.orglett.2c00697

Abstract

Herein, we report an on-DNA photoredox-mediated deaminative alkylation method for diversifying DNA-tagged acrylamide substrate with amine-derived radicals. The radicals can be conveniently generated from sterically hindered primary amines, and the deaminative alkylation can tolerate a broad array of radical precursors. Furthermore, the methodology is applicable to Boc-protected diamines, free amino acids, and aryl halides, which bear functional groups enabling additional rounds of diversification. The method is believed to offer a high potential for constructing DNA-encoded libraries, as was demonstrated by the production of a mock library in a 2 × 3 matrix format and confirmation of DNA stability by UPLC–MS and qPCR experiments.