Development of on-DNA vinyl sulfone synthesis for DNA-encoded chemical libraries

Abstract

We present the development of an efficient synthetic route to generate a DNA-compatible vinyl sulfone functional group, and the subsequent chemical transformations demonstrated the feasibility of our method in DEL construction.

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

“…To be suitable for DEL construction, this new on-DNA chemistry should leave the DNA tag integral for subsequent enzymatic ligation. [46][47][48] Therefore, an 18 bp double-stranded headpiece primer DNA was initially coupled with 4-formylbenzoic acid, followed by enzymatic ligation to give d1 (Scheme 5).…”

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.…”

Development of on-DNA Formation of Benzofuran for DNA-Encoded Library Synthesis

“…Innovative DEL synthesis has therefore been a major field of development in recent years. Many academic and industrial groups, including ours, have set their minds on the expansion of the DELT chemical toolbox to increase the chemical space available to DEL selection endeavors. Motivated by our latest reports showcasing the implementation of alkyne-based reactivities in DEL synthesis, , we turned our attention to the on-DNA synthesis of a significant but unchartered class of heterocycles.…”