Unsymmetrical polysulfidation via designed bilateral disulfurating reagents

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Sulfur-sulfur bonds are crucial in biological functions and drug development.
• Efficient and controlled synthesis of polysulfides with diverse functional groups remains a significant challenge.

Purpose of the Study:

• To design and synthesize a novel mesocyclic bilateral disulfurating reagent.
• To enable the sequential and modular installation of functional groups on polysulfide backbones.
• To demonstrate the reagent's utility in synthesizing unsymmetrical polysulfides and cross-linking biomolecules.

Main Methods:

• Design of a mesocyclic reagent exploiting S-O bond dissociation energy differences.
• Sequential reactions with various nucleophiles (C, N, S) to build polysulfide chains.
• Application in the cyclization of peptides to form cyclic disulfides.

Main Results:

• The reagent allows for the distinct and sequential installation of substituents on both sides of the sulfur-sulfur bond.
• Synthesis of six types of unsymmetrical polysulfides, including di-, tri-, and tetra-sulfides.
• Successful cross-linking of life-related molecules, natural products, and pharmaceuticals.
• Formation of 15- and 18-membered cyclic disulfide peptides from tri- and tetra-peptides.

Conclusions:

• The developed mesocyclic reagent provides an efficient and versatile platform for polysulfide synthesis.
• This method offers precise control over the structure and functionalization of polysulfides.
• The reagent has significant potential in drug design, peptide chemistry, and materials science.