FSO₂N₃-Mediated On-DNA Diazo-Transfer Chemistry

Area of Science:

• Chemical Biology
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• DNA-encoded libraries (DEL) are crucial for identifying drug leads.
• Existing DEL chemistry methods require optimization for efficiency and DNA compatibility.
• Developing novel reactions is essential for expanding the DEL toolbox.

Purpose of the Study:

• To develop a robust and straightforward DNA-compatible diazo-transfer reaction.
• To utilize FSO2N3 as a metal-free diazo-transfer reagent in solution.
• To ensure the reaction maintains high DNA fidelity for DEL applications.

Main Methods:

• A novel DNA-compatible diazo-transfer reaction was developed in solution.
• FSO2N3 was employed as the diazo-transfer reagent.
• The reaction's compatibility with various substrates and DNA fidelity was assessed.

Main Results:

• The reaction demonstrated high conversions and facile operation.
• The process was metal-free, preserving DNA integrity.
• Broad substrate scope, including aliphatic and aromatic amines, was achieved.
• High levels of DNA fidelity were maintained throughout the reaction.

Conclusions:

• The developed diazo-transfer reaction is a robust addition to the DNA-encoded library chemistry toolbox.
• This metal-free method provides convenient access to diverse amine building blocks for DEL.
• The technique supports efficient hit selection in drug discovery and basic research.