Synthesis of S-Glycoside Building Blocks as Mimetics of the Repeating d-GlcN-α-1,4-d-GlcA Heparan Sulfate Disaccharide

O’Shea, Conor; Miller, Gavin J.

Abstract

Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is a key regulator of biological processes. Owing to the inherent structural complexity of HS, structure-to-function studies with its ligands are required, and materials to improve the understanding of such interactions are therefore of high importance. Herein, the synthesis of novel S-linked GlcN-α(1→4)-GlcA disaccharide building blocks is detailed. Initial attempts at constructing the desired disaccharide using d-GlcN donors and d-Glc/GlcA acceptors via an S-glycosylation failed. Reversing the reactivity polarity of the monosaccharide building blocks enabled successful SN2 coupling using α-d-GlcN thiohemiacetals and d-galactosyl triflates. Subsequent C6-oxidation furnished the desired S-linked GlcN-α(1→4)-GlcA disaccharide building blocks on a gram scale. Such disaccharides offer potential for incorporation into wider synthetic HS sequences to provide glycomimetic tools.

Citation

O’Shea, C., & Miller, G. J. (2024). Synthesis of S-Glycoside Building Blocks as Mimetics of the Repeating d-GlcN-α-1,4-d-GlcA Heparan Sulfate Disaccharide. Molecules, 29(23), Article 5809. https://doi.org/10.3390/molecules29235809

• Journal Article Type: Article
• Acceptance Date: Dec 2, 2024
• Online Publication Date: Dec 9, 2024
• Publication Date: 2024-12
• Deposit Date: Jan 9, 2025
• Publicly Available Date: Jan 9, 2025
• Journal: Molecules
• Electronic ISSN: 1420-3049
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 23
• Article Number: 5809
• DOI: https://doi.org/10.3390/molecules29235809
• Public URL: https://keele-repository.worktribe.com/output/1021162