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.