The Sulfo-Click Reaction and Dual Labeling of Nucleosides

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Bioconjugation Chemistry

Background:

• Nucleoside derivatives are crucial in medicinal chemistry and molecular biology.
• Developing efficient bioconjugation strategies is essential for creating novel therapeutics and diagnostic tools.

Purpose of the Study:

• To present detailed synthetic procedures for the sulfo-click reaction applied to nucleoside derivatives.
• To demonstrate the versatility of the sulfo-click reaction for creating diverse nucleoside conjugates.
• To showcase a one-pot dual labeling strategy combining sulfo-click and copper-catalyzed azide-alkyne cycloaddition (CuAAC).

Main Methods:

• Conversion of 3'-O-TBDMS-protected nucleosides to 4'-thioacid derivatives.
• Chemoselective coupling of thioacid derivatives with sulfonyl azides.
• Synthesis of a bis-azido nucleoside for orthogonal labeling.
• One-pot dual labeling via sulfo-click/CuAAC cascade.

Main Results:

• Successful synthesis of 4'-thioacid-nucleoside derivatives.
• Efficient formation of various nucleoside conjugates using the sulfo-click reaction.
• Demonstration of a one-pot dual labeling protocol for nucleosides.
• High efficiency of the sulfo-click reaction in nucleoside bioconjugation.

Conclusions:

• The sulfo-click reaction provides a robust and efficient method for nucleoside modification.
• This methodology expands the toolkit for synthesizing complex nucleoside-based bioconjugates.
• The developed protocols offer new possibilities for applications in drug discovery and chemical biology.