The Synthesis of Aryl-β-C-Glycosides from Native Saccharides

Area of Science:

• Carbohydrate Chemistry
• Medicinal Chemistry
• Organic Synthesis

Background:

• β-C-glycosides are vital structural motifs in medicinal chemistry.
• Existing synthetic routes often lack efficiency or stereoselectivity.
• Developing accessible methods for β-C-glycoside synthesis is a key challenge.

Purpose of the Study:

• To develop a versatile and efficient synthesis of p-nitrophenol-β-C-glycosides.
• To utilize readily available native carbohydrates as starting materials.
• To achieve the desired β-stereochemistry exclusively.

Main Methods:

• A one-pot, two-step synthetic procedure was employed.
• Water was used as the sole solvent, promoting green chemistry principles.
• Native mono-, di-, and trisaccharides were used as substrates.

Main Results:

• The synthesis exclusively yielded the target β-C-glycosides.
• The procedure demonstrated high efficiency and stereoselectivity.
• A nanomolar SGLT2 inhibitor, [3-(4-ethylbenzyl)phenyl]-β-C-glucoside, was successfully synthesized.

Conclusions:

• The described method provides a facile and stereoselective route to p-nitrophenol-β-C-glycosides.
• This approach is versatile and applicable to complex carbohydrate structures.
• The synthesis is suitable for generating compounds with medicinal chemistry relevance, such as SGLT2 inhibitors.