Aryl diazonium intermediates enable mild DNA-compatible C-C bond formation for medicinally relevant combinatorial library synthesis.

ABSTRACT: Forging carbon-carbon (C-C) linkage in DNA-encoded combinatorial library synthesis represents a fundamental task for drug discovery, especially with broad substrate scope and exquisite functional group tolerance. Here we reported the palladium-catalyzed Suzuki-Miyaura, Heck and Hiyama type cross-coupling via DNA-conjugated aryl diazonium intermediates for DNA-encoded chemical library (DEL) synthesis. Starting from commodity arylamines, this synthetic route facilely delivers vast chemical diversity at a mild temperature and pH, thus circumventing damage to fragile functional groups. Given its orthogonality with traditional aryl halide-based cross-coupling, the aryl diazonium-centered strategy expands the compatible synthesis of complex C-C bond-connected scaffolds. In addition, DNA-t

SUBMITTER: Li X 

PROVIDER: S-EPMC9667928 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature