Zhi Zhou; Yuang Gu; Liexin Wu; Yan Wang; Huiying Xu; Lei Ma; Zhaoyong Zhang; Jincun Zhao; Wei Zhang; Wei Peng; Guang Yang; Xiyong Yu; Hongtao Xu; Wei Yi
SSRN, 2023
http://dx.doi.org/10.2139/ssrn.4342992

Abstract

Organo-Se species represent a type of increasingly important core motifs widely found in endogenous proteins and bioactive small molecules. Consequently, exploring their structural diversity to entrust the powerful potential both in synthesis and in application has emerged as an important endeavor in recent basic research, but it remains extremely limited and highly challenging. Here we realize either racemic or asymmetric synthesis towards a novel class of organo-Se species, namely benzothiaselenazole-1-oxides (BTSAs), and reveal its diversified applications mainly via fascinating click chemistry transformation. For synthesis, we developed the first sulfoximine pharmacophore-directed and rhodium(III)-catalyzed C-H/N-H annulative selenylation directly with simple elemental Se. For application, beyond those chemodivergent derivatizations derived by classical Se-mediated reactions, we found that BTSAs can be recognized as a new kind of click selenylation reagents, which not only enabled on-plate modular construction of parallel (1066 examples) and DNA-encoded (261 examples) brand-new indole-C3-selenide libraries, but also provided the site-specific modification of sulfhydryl-containing chemicals in applying as anti-COVID-19 drug discovery and bioorthogonal labeling-based HER2 fluorescence imaging analysis. The systemic work greatly expands the space of organo-Se chemistry and, given the unique performance of BTSAs in click selenylation, it should find robust application in organic synthesis, medicinal chemistry and chemical biology.