Microwave-Assisted Thioester-Empowered Toolkit for Modular Glycopeptide Synthesis

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Glycobiology

Background:

• Structurally precise glycopeptides and glycoproteins are essential for functional studies.
• Conventional methods for synthesizing glycosyl amino acids are inefficient and impractical for widespread use.

Purpose of the Study:

• To develop a novel and efficient platform for glycopeptide synthesis.
• To overcome the limitations of existing synthetic strategies for complex carbohydrates.

Main Methods:

• Development of a thioester-functionalized glycosyl amino acid building block.
• Utilization of a comprehensive reaction system including AgSbF6 activation, Oxyma additive, DIPEA base, and microwave irradiation.
• On-resin synthesis enabling rapid conversion and automation.

Main Results:

• Achieved rapid (10 min) and clean on-resin conversion of glycopeptides.
• Demonstrated broad effectiveness across diverse glycan structures and multiple peptide coupling sites (27 examples).
• Showcased seamless integration with enzymatic glycan elaboration and protein ligation for increased structural complexity.

Conclusions:

• The developed platform offers a robust and versatile approach to glycopeptide and glycoprotein synthesis.
• This method significantly broadens access to complex glycopeptides and glycoproteins.
• Provides a powerful entry point for advancements in functional glycoscience and biomedical discovery.