Pseudo-glycoconjugates with a C-glycoside linkage

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Glycobiology

Background:

• Pseudo-glycans, with C-glycosidic linkages replacing O-glycosidic ones, resist degradation by cellular glycoside hydrolases.
• These stable analogs are promising molecular tools for sustained biological activity within cells.
• Limited synthesis and understanding of pseudo-glycans hinder exploration of their full biological potential.

Purpose of the Study:

• To review recent studies on creating C-glycoside analogs of ganglioside GM3 using a CHF-sialoside linkage.
• To summarize chemical insights from the stereoselective synthesis of the C-sialoside bond, yielding pseudo-GM3.
• To develop streamlined synthesis methods for pseudo-glycan analogs.

Main Methods:

• Stereoselective synthesis of C-sialoside bonds to create pseudo-GM3 analogs.
• Conformational analysis of synthesized CHF-sialoside disaccharides.
• Development of a direct C-glycosylation method utilizing atom-transfer radical coupling.

Main Results:

• Successful synthesis of pseudo-GM3 analogs based on the CHF-sialoside linkage.
• Conformational analysis confirmed successful conformational control via F-atom introduction.
• Synthesized pseudo-glycans demonstrated enhanced biological activity compared to natural counterparts.

Conclusions:

• Pseudo-glycans, particularly pseudo-GM3 analogs, offer enhanced biological activity and stability.
• The developed C-glycosylation method using atom-transfer radical coupling streamlines synthesis.
• These findings pave the way for broader applications of pseudo-glycans as molecular tools.