Selectivity control in the reaction between 2-hydroxyarylaldehydes and 4-hydroxycoumarin. Antioxidant activities and computational studies of the formed products

A series of 6H,7H-7-(4-Hydroxy-3-coumarinyl)[1]benzopyrano[4,3-b][1]benzopyran-6-ones 4a-g and 3-(2-hydroxybenzoyl)-2H-chromen-2-ones 5a-g derivatives were synthesized by reaction of 4-hydroxycoumarin with 2-hydroxyarylaldehydes 2a-f or 2-hydroxynaphtaldehyde 2g using different solvents and acid/base catalysts. The approach relies on a regioselective cascade reaction involving one/two molar equiv of the 4-hydroxy coumarin iteratively acting as active methylene substrate in a Knoevenagel condensation and in a Michael addition. The structures of all compounds were established by IR, mass spectrometry, 1H-NMR and 13C-NMR. Antioxidant activity of the synthesized compounds were determined using the DPPH scavenging assay, best results being obtained with 5b (IC50 = 236 µg/mL). Computational studies showed that the compounds bind in the ATP-binding site of p38 MAPK, in a same manner than known polyaromatic potent inhibitors. The synthesized compounds might be considered further for cancer therapy. [Display omitted]