Enantioselective Synthesis of Chiral Sulfonimidoyl Fluorides Facilitates Stereospecific SuFEx Click Chemistry.

Autor: Huang HS; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Yuan Y; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Wang W; Key Laboratory of Chemical Metrology and Applications on Nutrition and Health for State Market Regulation, Beijing, 100029, China., Zhang SQ; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Nie XK; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Yang WT; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Cui X; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Tang Z; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China., Li GX; Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan, 610041, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Nov 04, pp. e202415873. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1002/anie.202415873
Abstrakt: Sulfur-centered electrophilic 'warheads' have emerged as key components for chemical proteomic probes through sulfur-exchange chemistry (SuFEx) with protein nucleophiles. Among these functional groups, sulfonimidoyl fluorides (SIFs) stand out for their modifiable sites, tunable electrophilicities, and chiral sulfur-center, presenting exciting possibilities for new covalent chemical probes. However, the synthetic access to chiral SIFs has been a challenge, limiting their exploration and applications. In this study, we describe a convenient route to obtain chiral SIFs from readily available sulfenamides via a series of one-pot tandem reactions with high enantiomeric excess (ees). The resulting chiral SIFs were further converted into a diverse array of chiral S(VI) derivatives under mild conditions or in buffer solutions. Most significantly, the specificity of the chiral SIFs in protein ligation experiments underscored the critical role of sulfur-center chirality in the design and screening of more-selective covalent probes and therapeutics.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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