Highly efficient synthesis of two hyaluronan trisaccharide analogues for potential hyaluronic acid synthases inhibitors

The syntheses of two hyaluronan trisaccharide analogues, naphthyl O-(3-methoxy-β-D-glucopy-ranosyluronic acid)-(1, 3)-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1, 4)-O-β-D-glucopyranosyluronic acid and naphthyl O-(3-methoxy-2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1, 4)-O-(β-D-glucopyranosyluronic acid)-(1, 3)-O-2-acetamido-2-deoxy-β-D-glucopyranoside, were described. Construction of the target molecules was achieved through a combination of BF₃·Et₂O/toluene system and trichloroacetimidate glycosylation methodology. This is the first report on the synthesis of the 3-methoxyl derivatives, which represent the smallest fragments that incorporate all the structural features of polymeric hyaluronan and can be used for potential hyaluronic acid synthases inhibitors.