The synergic effect of the chitosan biomacromolecule support for catalyzing of Hantzsch esters formation by CuSO has been demonstrated for one-pot and efficient pseudo-four-component reaction to afford a wide range of 1,4-dihydropyridine (DHP) or polyhydroquinoline (PHQ) derivatives. The desired products were simply prepared from different aldehydes, β-dicarbonyls and ammonium acetate in the presence of a low loading of chitosan supported copper(II) sulfate (CSCS) in EtOH under reflux conditions. The biodegradable CSCS catalyst was characterized by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy analysis (EDX) methods as well as coupled plasma-atomic emission (ICP-AE) and FT-IR spectroscopy. The CSCS catalyst is recyclable and reused four times without significant loss of its activity.