Reactivity Tuning by Ring Size: A Glycosylation Protocol Using Thiophene-Scaffolded Glycosyl Donors

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Glycochemistry

Background:

• Developing versatile glycosyl donors is crucial for efficient oligosaccharide synthesis.
• Existing methods often require complex activation conditions or lack fine-tuned reactivity control.
• The classical Yu's donor, while effective, has limitations in certain synthetic scenarios.

Purpose of the Study:

• To develop a novel thiophene-scaffolded alkyne-activating glycosyl donor.
• To achieve fine reactivity control through ring-size modulation.
• To enable efficient one-pot oligosaccharide assembly and orthogonal glycosylation strategies.

Main Methods:

• Synthesis of a thiophene-based alkyne-activating glycosyl donor (ATC donor).
• Investigation of reactivity through ring-size modulation.
• Demonstration of one-pot oligosaccharide assembly under single activation conditions.
• Exploration of reactivity-based orthogonal glycosylation strategies.

Main Results:

• Successful development of a thiophene-scaffolded alkyne-activating glycosyl donor.
• Demonstrated fine reactivity control via ring-size modulation.
• Achieved efficient one-pot oligosaccharide assembly under single activation.
• Showcased reactivity differentiation supporting orthogonal glycosylation.
• The ATC donor proved readily prepared, bench-stable, and broadly applicable.

Conclusions:

• The thiophene-based ATC donor provides a practical and tunable platform for programmable glycosylation.
• Its distinct reactivity, compared to classical donors, facilitates efficient and versatile oligosaccharide synthesis.
• This development opens new avenues for complex carbohydrate construction.