Bilateral Unsymmetrical Disulfurating Reagent Design for Polysulfide Construction

Area of Science:

• Life Science
• Pharmaceutical Science
• Materials Science

Background:

• Polysulfides are crucial in various scientific fields.
• Constructing complex polysulfides with specific structures is challenging due to the reversible nature of the sulfur-sulfur (S-S) bond.

Purpose of the Study:

• To develop a method for the controllable sequential installation of groups on both ends of the S-S motif.
• To create a library of bilateral unsymmetrical disulfurating reagents for synthesizing unsymmetrical disulfides and trisulfides.

Main Methods:

• Established a library of bilateral unsymmetrical disulfurating reagents (R1O-SS-SO2R2) with divergent mask groups.
• Utilized sequential coupling by controlling the activation of S-SO2 (37.6 kcal/mol) and S-O (54.8 kcal/mol) bonds in the presence of the S-S bond (62.0 kcal/mol).

Main Results:

• Successfully achieved successive reactions at each end of the S-S motif.
• Synthesized unsymmetrical disulfides and trisulfides.
• Demonstrated the cross-linkage of natural products, pharmaceuticals, peptides, and bovine serum albumin.

Conclusions:

• The developed method offers a robust strategy for constructing unsymmetrical polysulfides.
• This approach facilitates the synthesis of complex sulfur-containing molecules for diverse applications.
• The ability to selectively functionalize the S-S bond opens new avenues in drug discovery and materials development.