Sunday, January 6, 2019

Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Lisa Marie Kammer, Benjamin Lipp, and Till Opatz
The Journal of Organic Chemistry, 2019
DOI: 10.1021/acs.joc.8b02759

The synthesis of vinyl sulfones and (α,β-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777.

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