Polysulfurating reagent design for unsymmetrical polysulfide construction

Abstract

From life science to material science, to pharmaceutical industry, and to food chemistry, polysulfides are vital structural scaffolds. However, there are limited synthetic methods for unsymmetrical polysulfides. Conventional strategies entail two pre-sulfurated cross-coupling substrates, R–S, with higher chances of side reactions due to the characteristic of sulfur. Herein, a library of broad-spectrum polysulfurating reagents, R–S–S–OMe, are designed and scalably synthesized, to which the R–S–S source can be directly introduced for late-stage modifications of biomolecules, natural products, and pharmaceuticals. Based on the hard and soft acids and bases principle, selective activation of sulfur-oxygen bond has been accomplished via utilizing proton and boride for efficient unsymmetrical polysulfuration. These polysulfurating reagents are highlighted with their outstanding multifunctional gram-scale transformations with various nucleophiles under mild conditions. A diversity of polysulfurated biomolecules, such as SS−(+)-δ-tocopherol, SS-sulfanilamide, SS-saccharides, SS-amino acids, and SSS-oligopeptides have been established for drug discovery and development.

Glycosyl disulfides: importance, synthesis and application to chemical and biological systems

“…Since sulfur and oxygen exhibit similar electronic effects, the challenge of this approach was to distinguish between the S-O bond cleavage over the S-S bond which in turn was overcome by employing a hard acid like tris( perfluorophenyl)borane directly coordinated to the oxygen. 59 In summary, carbohydrate dithioperoxyesters (RSSAc) have been shown to be valuable disulfurating reagents to efficiently access unsymmetrical glycosyl disulfides.…”

Steric and stereoscopic disulfide construction for cross-linkage via N-dithiophthalimides

“…To meet diverse requirements, masked disulfurating reagents (RSSAc and RSSOMe) were developed by us to incorporate RSS moieties into multifarious systems (Scheme 1c). 14,15 Considering the great importance of steric and stereoscopic disuldes, we are intrigued by disulfuration of a-branched esters to access diverse hindered disuldes. Nevertheless, steric hindrance of a-branched esters is the rst barrier for disulfuration.…”

Freeze the dynamicity: charge transfer complexation assisted control over the reaction pathway

“…25,26 Thus, methodologies to prepare asymmetric disuldes generally involve functional groups other than thiols and special reagents/reaction conditions. 21,22,[27][28][29] For the present work, we chose thiol (-SH) as the reactive group based on these facts and also to develop a simple methodology to create asymmetric disuldes exclusively from two different thiols.…”