An alternative approach utilises chlorosulfonic acid, which has been applied for the sulfation of polysaccharides, phenolic acids, and flavonoids amongst others. Agarose sulfate, an example of sulfated seaweed polysaccharide which was proposed to have an anticoagulant activity comparable to heparin. Youping and co-workers have reported the formation of agarose sulfate using the chlorosulfonic acid protocol. Agarose polysaccharide was dissolved in formamide solvent followed by the addition of chlorosulfonic acid/pyridine solution and stirred for 4 h at 65 °C affording agarose sulfate (Scheme 3).