Visible Light-Promoted Divergent Benzoheterocyclization from Aldehydes for DNA-Encoded Chemical Libraries

Abstract

Benzoheterocyclics have been widely adopted as drug-like core scaffolds that can be incorporated into DNA-encoded chemical library technology for high-throughput hit discovery. Here, we present a visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes. Four types of DNA-conjugated benzoheterocyclics were obtained under mild conditions with a broad substrate scope. A cross substrate scope study, together with enzymatic ligation and subsequent chemical diversifications, were conducted, demonstrating the feasibility of this approach in DNA-encoded chemical library construction.

Recent Scenario for the Synthesis of Benzimidazole Moiety(2020–2022)

“…Notably, this open‐air operation does not require an inert atmosphere, providing benefits for practical implementation (scheme 40). [43] …”

Incorporation of viridicatin alkaloid-like scaffolds into DNA-encoded chemical libraries

“…20 Having seen the broad scope of both isatins and DNAtagged aldehydes examined, we further attempted to carry out chemical transformations based on these DNA-tagged viridicatin derivatives. A palladium-catalyzed Suzuki coupling 43,44 successfully converted the bromide substituent in c10 into a phenyl ring, yielding >90% conversion (see the ESI †). The hydroxy group plays an important role in different pharmacological activities, as showcased in Scheme 1A.…”

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

“…Attracted by the DEL's cost and time efficiency, both academia and pharmaceutical companies have advanced DEL in terms of synthetic methodology and selection strategy. 18–31 Currently, although very few drug candidates in late-stage clinical trials stemmed from DEL, such as the soluble epoxide hydrolase (sEH) inhibitor GSK2256294 and the receptor-interacting protein (RIP1) kinase inhibitor GSK2982772, 32–35 DELs have shown their potential in high-throughput discovery of preliminary bioactive hits for defined targets, which might lead to the development of bioactive compounds or probes with structural optimization.…”