Expediated synthesis of N-acyl-N-alkyl sulfonamide probes for protein proximity labelling

Abstract

N-Acyl-N-alkysulfonamides (NASAs) can be used to site-selectively label proteins via proximitymediated reactions. However, the synthesis of NASA probes can be challenging, typically using a two-step synthetic route that relies on alkylation of a weakly nucleophilic acyl-sulfonamide intermediate. Here, we develop a novel one-step strategy for NASA synthesis from a common alkyl-sulfonamide intermediate, overcoming these challenges. A series of NASA probes bearing common labels for protein modification are efficiently synthesized, in a single step, from the corresponding carboxylic acid. This method will increase the accessibility and versatility of these powerful reagents, and the applications of proximity-mediated protein labelling.