Enabling Modular Click Chemistry Library through Sequential Ligations of Carboxylic Acids and Amines.
Angew Chem Int Ed Engl
; 63(40): e202410699, 2024 Oct 01.
Article
de En
| MEDLINE
| ID: mdl-38943043
ABSTRACT
High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double-click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO2NCO) via a modular amidation/SuFEx (sulfur-fluoride exchange) process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO2F) and N-acylsulfamides (RCONHSO2NR'R'') in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram-positive bacterium S. aureus and drug-resistant MRSA (MIC up to 6.25â
µg â
mL-1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Acides carboxyliques
/
Bibliothèques de petites molécules
/
Chimie click
/
Amines
Langue:
En
Journal:
Angew Chem Int Ed Engl
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Allemagne