Synthetic α,β(1→4)-Glucan Oligosaccharides as Models for Heparan Sulfate

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Abstract
α,β-(1→4)-Glucans were devised as models for heparan sulfate with the simplifying assumptions that carboxyl-reduction and sulfation of heparan sulfate does not decrease the SMC antiproliferative activity and that N-sulfates in glucosamines can be replaced by O-sulfates. The target oligo-saccharides were synthesized using maltosyl building blocks. Glycosylation of methyl 2,3,6,2′,3′,6′-hexa-O-benzyl-β-maltoside (1) with hepta-O-acetyl-α-maltosyl bromide (2) furnished tetrasaccharide 3 which was deprotected to α-D-Glc-(1→4)-β-D-Glc-(1→4)-α-D-Glc-(1→4)-β-D-Glc-(1→OCH3) (5) or, alternatively, converted to the tetrasaccharide glycosyl acceptor (8) with one free hydroxyl function (4‴′-OH). Further glycosylation with glucosyl or maltosyl bromide followed by deblocking gave the pentasaccharide [β-D-Glc-(1→4)-α-D-Glc-(1→4)]2-β-D-Glc-(1→OCH3) (11) and hexasaccharide [α-D-Glc-(1→4)-β-D-Glc-(1→4)2-α-D-Glc-(1→4)-β-D-Glc-(1→OCH3) (14). The protected tetrasaccharide 3 and hexasaccharide 12 were fully characterized by 1H and 13C NMR spectroscopy. Assignments were possible using 1D TOCSY, T-ROESY, 1H,1H 2D COSY supplemented by 1H-detected one-bond and multiple-bond 1H,13C 2D COSY experiments.