Stereoselective and Divergent Construction of β-Thiolated/Selenolated Amino Acids via Photoredox-Catalyzed Asymmetric Giese Reaction

• DOI: 10.1021/jacs.0c04994
• Publication Date: 2020-07-27T13:46:38Z
• Authors: Hongli Yin; Mengjie Zheng; Huan Chen; Siyao Wang; Qingqing Zhou; Qiang Zhang; Ping Wang
• Keywords: Enantiopure drug; Photoredox catalysis; Peptide Synthesis; Bioconjugation

Sulfur and selenium occupy a distinguished position in biology owing to their redox activities, high nucleophilicity, acyl transfer capabilities. Thiolated/selenolated amino acids, including cysteine, selenocysteine, derivatives, play critical roles regulating the conformation function of proteins serve as an important motif for peptide design bioconjugation. Unfortunately, general concise method attain enantiopure β-thiolated/selenolated acids remains unsolved problem. Herein, we present photoredox-catalyzed asymmetric preparation using simple chiral auxiliary, which controls diastereoselectivity key alkylation step acts orthogonal protecting group subsequent synthesis. Our protocol can be used prepare wide range on gram scale, would otherwise difficult obtain conventional methods. The effect our chemistry was further highlighted validated through series peptidyl thiol/selenol analogues, cytochrome c oxidase subunit protein 7C oxytocin.