The Sulfo‐Click Reaction and Dual Labeling of Nucleosides

Abstract

This article contains detailed synthetic procedures for the implementation of the sulfo-click reaction to nucleoside derivatives. First, 3-O-TBDMS-protected nucleosides are converted to their corresponding 4-thioacid derivatives in three steps. Then, various conjugates are synthetized via a biocompatible and chemoselective coupling procedure using sulfonyl azide partners. Finally, to illustrate the potential of the sulfo-click reaction, a nucleoside bearing two orthogonal azido groups is synthesized and engaged in one-pot dual labeling through a sulfo-click/copper-catalyzed azide-alkyne cycloaddition (CuAAC) cascade. The high efficiency of the sulfo-click reaction as applied to nucleosides opens up new possibilities in the context of bioconjugation.

Facile access to 4′-(N-acylsulfonamide) modified nucleosides and evaluation of their inhibitory activity against SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14

“…30 In this context, we have recently exploited the sulfo-click reaction between 4′-thioacid nucleosides and various sulfonyl azides for preparing 5′-bioconjugated nucleosides. 31,32 The reaction that leads to the formation of an N-acylsulfonamide in aqueous media was found to be efficient, rapid and biocom-patible under catalyst-free conditions. Given the simplicity with which this method allows access to N-acylsulfonamides, we describe here the synthesis and biological evaluation of 20 original 4′-(N-acylsulfonamide) adenosine derivatives.…”

N-Acylsulfonamide: a valuable moiety to design new sulfa drug analogues

“…The sulfo-click reaction between a sulfonyl azide and a thioacid represents a valuable alternative to access N-acylsulfonamide derivatives with high efficiency. [36][37][38][39][40][41] We recently explored this reaction for the generation of 5′bioconjugated nucleosides 42,43 and the synthesis of 4′-(Nacylsulfonamide) modified nucleosides as SARS-CoV-2 RNA cap N7-guanine-methyltransferase nsp14 inhibitors. 44 This catalyst-free reaction proved to be fast and efficient under aqueous conditions with an extremely simple implementation.…”