Sulfoform generation from an orthogonally protected disaccharide

An orthogonally protected disaccharide (GlcN(α1→4)Glc) with a β-linked 2′-aminoethyl linker was used to generate a series of sulfated derivatives (sulfoforms), with a 6-O-sulfate on the glucose residue and one or more sulfate esters on the terminal glucosamine. Deprotection and sulfonation steps were performed in solution and in variable order, with isolated yields of 36–54% (85–90% per operation) after HPLC purification. The modular deprotection–sulfonation sequences can be performed with efficient recovery of the polysulfate products, and avoids complications associated with heterogeneous reactivity in solid-phase synthesis.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of an orthogonally protected disaccharide (GlcN(α1→4)Glc) with 2′-aminoethyl linker. ► Generation of sulfoforms with a 6-O-sulfate on glucose and multiple sulfate esters on glucosamine. ► Deprotection and sulfonation steps performed in variable order with 85–90% yield per operation. ► Microwave-assisted sulfonation provides significant improvement to overall yields.