Solvent-Free Synthesis of Five Membered Heterocycles from Chalcones and their Biological Evaluation for Anti-Hyperglycaemic Activity

Abstract

T he development of environmentally friendly and efficient protocol for the synthesis of heterocyclic compounds is the current demand of synthetic community. Solvent-free synthesis has emerged as a sustainable approach reducing waste generation, and minimizing environmental impact. In this connection, we have developed a solvent-free method for the construction of five membered heterocycles i.e. isoxazoline and pyrazoline from α, β-unsaturated carbonyl compounds and Hydrazine/hydroxylamine hydrochloride. This protocol involves the [3+2] cycloaddition reaction between α, β-unsaturated carbonyl compounds and hydrazine hydrochloride/hydroxylamine hydrochloride under solvent free conditions to provide the substituted isoxazoline and pyrazoline in excellent yields. The synthesized compounds were characterized through 1H NMR, 13C NMR, Mass spectral data and IR. These newly synthesized compounds were screened for their antihyperglycemic activity using sucrose loaded diabetic model. Isoxazoline derivatives offered potent antihyperglycemic response than correspondence pyrazoline derivatives. Compounds bearing isoxazoline ring II A and II E showed maximum % fall of blood glucose level than control group which was comparable to the standard drug metformin. The newer compounds VIA, VIB, and VIC also evaluated for their anti-hyperglycemic activities, compound VIC showed appreciable response (62.5% antihyperglycemic activity).