Metal-Free, Photoinduced On-DNA Synthesis of β-Hydroxy Sulfides

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• β-hydroxy sulfides are crucial pharmacophores in drug development.
• Existing DNA-encoded library (DEL) methodologies have limitations in accessing these structures.
• Novel synthetic strategies are needed to expand the chemical space for drug discovery.

Purpose of the Study:

• To develop a metal-free photochemical strategy for synthesizing on-DNA β-hydroxy sulfides.
• To enable the efficient construction of diverse DNA-encoded libraries (DELs).
• To expand the accessible chemical space for identifying novel therapeutics.

Main Methods:

• A novel metal-free photochemical hydrothiolation reaction.
• Utilizing broad substrate scope with various thiols and olefins.
• Demonstrating excellent DNA compatibility for on-DNA synthesis.

Main Results:

• Successful synthesis of on-DNA β-hydroxy sulfides.
• Broad substrate scope demonstrated for both thiols and olefins.
• Efficient construction of diverse DNA-encoded libraries (DELs).

Conclusions:

• The developed photochemical strategy provides a new metal-free route to on-DNA β-hydroxy sulfides.
• This method significantly expands the accessible chemical space for drug discovery.
• It offers a valuable new tool for identifying novel therapeutic agents.