SnCl2-catalyzed Kabachnik–Fields synthesis of α-aminophosphonates with potent antioxidant activity

Abstract

A novel and efficient method for synthesizing α-aminophosphonates was developed through a Kabachnik–Fields multicomponent reaction using 6-aminocoumarin or 6-aminobenzodioxane, benzaldehyde, triethyl phosphite, and a catalytic amount of SnCl₂ in ethanol. The resulting 25 compounds 1a–l (71–92%) and 6a–m (45–96%) were obtained in moderate to excellent yields. Antioxidant activity, assessed via the FRAP and CUPRAC assays, the results demonstrated that several of these compounds exhibit comparable or even superior reducing power to ascorbic acid, particularly at low concentrations. These findings underscore the potential of these α-aminophosphonates as promising antioxidant agents for future applications. ADME analysis predicts good oral bioavailability, limited brain and skin penetration, and potential CYP450 inhibition.