Cycloadditions as a Sweet Route to 'Double C-Glycosylation'

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Natural Product Synthesis

Background:

• Many pharmaceuticals, including antibiotics like erythromycin and SGLT inhibitors (e.g., Bexagliflozin, Sotagliflozin), are glycosylated.
• Glycosylation enhances bioactivity and bioavailability of natural products and is crucial for SGLT inhibitor binding.
• While single C-glycoside linkages are common, double C-glycosylation is rare in nature, with its mechanism unknown.

Purpose of the Study:

• To explore and develop a biomimetic procedure for synthesizing double C-glycosylated compounds.
• To investigate intermolecular cycloaddition chemistry for creating these complex structures.
• To generate novel bridged polycyclic ethers from a specific precursor.

Main Methods:

• Utilized a maltol-derived oxidopyrylium salt as a common precursor.
• Employed intermolecular cycloaddition chemistry.
• Developed a potentially biomimetic synthetic strategy.

Main Results:

• Successfully accessed new double C-glycosylated products.
• Enabled the creation of bridged polycyclic ethers.
• Demonstrated a novel synthetic route inspired by natural processes.

Conclusions:

• The developed procedure offers a new pathway to synthesize complex double C-glycosylated molecules.
• This biomimetic approach provides insights into the potential formation of such structures in nature.
• The method yields valuable bridged polycyclic ether scaffolds for further chemical exploration.