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. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: General protocol for the synthesis of 4′-thioacid-nucleoside derivatives

Basic Protocol 2: Implementation of the sulfo-click reaction

Basic Protocol 3: Synthesis of 3′-azido-4′-(carboxamido)ethane-sulfonyl azide-3′-deoxythymidine

Basic Protocol 4: Detailed synthetic procedure for one-pot double-click conjugations