Photoactivatable Electrophilic Glycosylselenosulfonates for Ultrafast Modification of Alkynes and Thiols

Glycosylseleno scaffolds exhibit wide-ranging applications in multidisciplinary fields, particularly in drug discovery and biophysical chemistry, where they serve as valuable tools for biomolecular structural analysis. However, efficient methods toward glycosylseleno scaffolds remain underexplored. Herein, we present the design of a novel class of bench-stable reagents, glycosylselenosulfonates, which uniquely integrate radical reactivity with electrophilic properties, thereby facilitating the straightforward incorporation of glycosylseleno moieties under mild reaction conditions. Upon photoirradiation, the radical addition of alkynes with glycosylselenosulfonates proceeds at an exceptionally fast rate, achieving completion in less than 1 min. Likewise, the functionalization of cysteine-containing molecules is achieved in a comparably short time frame, typically within 1 min in most instances. Additive experiments involving various amino acids confirm the robustness of these transformations, demonstrating consistently high efficiency across diverse reaction environments with negligible interference. Importantly, successful peptide and protein labeling in aqueous conditions highlights the method’s potential for bioorthogonal applications. These findings collectively underscore the broad applicability and operational simplicity of glycosylselenosulfonates in developing rapid and efficient labeling techniques for biological and chemical research. This work not only advances synthetic methodologies for glycosylseleno scaffolds but also opens new avenues for functional studies of complex biological systems.

Bench-stable glycosylselenosulfonates reagents enable ultrafast (1 min) labeling of cysteine-containing biomolecules and alkynes under mild, aqueous conditions for bioorthogonal applications.