Résumé
Click reactions are fast, chemoselective, and high-yielding covalent reactions between tworeactive functions without generating armless byproducts.1Such ideal reactions have found awide range of applications2in particular in the context of bioorthogonal chemistry.3 Althoughthe number of click reactions available has considerably grown over the past twenty years, thetoolbox continues to rise and improvements are still required to achieve compatible reactionsin a biological environment.The sulfo-click reaction is an emergent surrogate click reaction involving a thioacid thatreacts specifically with a sulfonyl azide leading to the formation of a N-acylsulfonamidelinkage. The sulfo-click reaction fulfills the criteria of click reactions, generates only sulfurand dinitrogen as byproducts and is compatible with aqueous conditions. These characteristicsare of particular interest in the field of nucleic acid chemistry. We recently developed thesynthesis of original 4′-thioacid nucleoside analogues that opened the way to new interestingapplications of the sulfo-click reaction.We will present our endeavor taking advantage of the biorthogonality of the sulfo-clickreaction for bioconjugation.5Indeed, a variety of sulfonyl azide derivatives were successfullyconjugated to 4’-thioacid nucleosides under aqueous biocompatible conditions. Then, theinteresting properties of the N-acylsulfonamide linkage in the field of medicinal chemistry6were exploited to synthesize new cyclic dinucleotides for potential therapeutic applications byactivating the native immune response.