Light-induced β-hydroxy sulfone synthesis in DNA-encoded libraries

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• DNA-encoded libraries (DELs) are powerful tools for drug discovery.
• Efficient synthesis of diverse chemical scaffolds is crucial for DEL construction.
• Metal-catalyzed reactions are common but can be limited by substrate scope and purification.

Purpose of the Study:

• To develop a novel, metal-free method for synthesizing Csp³-rich scaffolds for DNA-encoded libraries.
• To explore the visible-light photooxidation of sulfinate salts with alkenes.
• To establish a straightforward and efficient route to β-hydroxy sulfones on DNA.

Main Methods:

• Visible-light photoredox catalysis was employed.
• Sulfinate salts were reacted with common alkenes under irradiation.
• The reaction was performed on DNA-conjugated small molecules.
• Product characterization involved standard analytical techniques.

Main Results:

• The reaction successfully yielded β-hydroxy sulfones.
• Broad substrate compatibility was observed for both sulfinate salts and alkenes.
• Conversion rates ranged from moderate to excellent.
• The method proved efficient and straightforward for DNA-encoded library synthesis.

Conclusions:

• A novel, metal-free visible-light photooxidation enables the synthesis of β-hydroxy sulfones.
• This method provides an efficient route to Csp³-rich DNA-encoded libraries.
• The approach offers broad applicability and simplifies library construction for drug discovery.