Shivani Patel; Shorouk O. Badir; Gary A. Molander
Trends Chem., 2021, 3(3), 161-175
https://doi.org/10.1016/j.trechm.2020.11.010

Abstract

Recently, DNA-encoded library (DEL) technology has emerged as an innovative screening modality for the rapid discovery of therapeutic candidates in pharmaceutical settings. This platform enables a cost-effective, time-efficient, and large-scale assembly and interrogation of billions of small organic ligands against a biological target in a single experiment. An outstanding challenge in DEL synthesis is the necessity for water-compatible transformations under ambient conditions. To access uncharted chemical space, the adoption of photoredox catalysis in DELs, including Ni-catalyzed manifolds and radical/polar crossover reactions, has enabled the construction of novel structural scaffolds through regulated odd-electron intermediates. Herein, a critical discussion of the validation of photoredox-mediated alkylation in DEL environments is presented. Current synthetic gaps are highlighted and opportunities for further development are speculated upon.