Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications
Marek Baráth,
Steen U. Hansen,
Charlotte E. Dalton,
Gordon C. Jayson,
Gavin J. Miller,
John M. Gardiner
Affiliations
Marek Baráth
Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK
Steen U. Hansen
Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK
Charlotte E. Dalton
Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK
Gordon C. Jayson
Institute of Cancer Sciences, Christie Hospital and University of Manchester, Wilmslow Road, Manchester M20 4BX, UK
Gavin J. Miller
Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK
John M. Gardiner
Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK
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.
