Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications

Baráth, Marek; Hansen, Steen U.; Dalton, Charlotte E.; Jayson, Gordon C.; Miller, Gavin J.; Gardiner, John M.

Abstract

Heparin and heparan sulphate (H/HS) are important members of the glycosaminoglycan family of sugars that regulate a substantial number of biological processes. Such biological promiscuity is underpinned by hetereogeneity in their molecular structure. The degree of O-sulfation, particularly at the 6-position of constituent D-GlcN units, is believed to play a role in modulating the effects of such sequences. Synthetic chemistry is essential to be able to extend the diversity of HS-like fragments with defined molecular structure, and particularly to deconvolute the biological significance of modifications at O6. Here we report a synthetic approach to a small matrix of protected heparin-type oligosaccharides, containing orthogonal D-GlcN O-6 protecting groups at programmed positions along the chain, facilitating access towards programmed modifications at specific sites, relevant to sulfation or future mimetics.

Citation

Baráth, M., Hansen, S. U., Dalton, C. E., Jayson, G. C., Miller, G. J., & Gardiner, J. M. (2015). Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications. Molecules, 20(4), 6167 - 6180. https://doi.org/10.3390/molecules20046167

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2015
• Online Publication Date: Apr 9, 2015
• Publication Date: Apr 9, 2015
• Publicly Available Date: May 26, 2023
• Journal: Molecules
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 4
• Pages: 6167 - 6180
• DOI: https://doi.org/10.3390/molecules20046167
• Keywords: heparin, oligosaccharide, iduronate, GAG mimetic
• Publisher URL: http://www.mdpi.com/1420-3049/20/4/6167