Sequential Regiodivergent Polyol Sulfonylation and Functionalization Enable Precise Engineering of Carbohydrates

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Catalysis

Background:

• Regioselective functionalization of unprotected carbohydrates is difficult due to similar hydroxyl group reactivities.
• Existing methods lack efficient strategies for site-specific modification of polyols.
• Controlled synthesis of complex carbohydrates and glycoconjugates remains a significant challenge.

Purpose of the Study:

• To develop an efficient protocol for site-specific modification of carbohydrates.
• To establish a regiodivergent polyol tagging and functionalization strategy.
• To enable precise synthesis of rare sugars, deoxy/amino sugar analogues, and complex oligosaccharides.

Main Methods:

• Development of two complementary Ag2CO3-ligand-based regimes for regioselective sulfonylation.
• Control of regioselectivity by toggling the presence of a palladium ([Pd]) catalyst.
• Utilized competition experiments and Density Functional Theory (DFT) simulations to elucidate reaction mechanisms.

Main Results:

• Achieved regioselective sulfonylation of cis- and trans-diols in carbohydrates.
• Palladium ([Pd]) catalyst directs sulfonylation to equatorial C3-OH groups via cis-diol complexation.
• Silver (Ag-(I)) complex without [Pd] directs sulfonylation to the typically inert axial hydroxyl of cis-1,2-diols.

Conclusions:

• The dual-catalytic approach provides a robust platform for precision carbohydrate engineering.
• Sulfonylated products serve as versatile synthons for diverse structural derivations and glycosylations.
• Advances the efficient synthesis of biologically relevant oligosaccharides and glycoconjugates.