An access to various sulfation patterns in dermatan sulfate: chemical syntheses of sulfoforms of trisaccharide methyl glycosides Original Research Article

The syntheses are reported for the first time of α-l-IdopA2SO3-(1→3)-β-d-GalpNAc4SO3-(1→4)-α-l-IdopA2SO3-(1→OMe), its disulfated analogue α-l-IdopA2SO3-(1→3)-β-d-GalpNAc-(1→4)-α-l-IdopA2SO3-(1→OMe), and of β-d-GalpNAc4SO3-(1→4)-α-l-IdopA2SO3-(1→3)-β-d-GalpNAc4SO3-(1→OMe), which represent structural fragments of dermatan sulfate, unavailable directly by chemical or enzymatic degradation of the glycosaminoglycan polymer. These molecules were readily obtained from a pair of key disaccharide intermediates, in which the relative difference of stability of the d-GalNAc 4-hydroxy protecting groups (acetate or pivalate) toward saponification conditions allowed access to various sulfoforms from a common precursor. For the preparation of these blocks, the 4-O-pivaloyl-d-galacto moiety was readily obtained through a one-pot stereospecific intramolecular nucleophilic displacement on an easily available 3-O-pivaloyl-d-gluco precursor, and the l-IdoA moiety through selective radical oxidation at C-6 of a l-ido 4,6-diol derivative with oxoammonium salts.