2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran: Design and Evaluation as a Novel Radical-Scavenging Antioxidant against Lipid Peroxidation

To develop a novel potent radical-scavenging antioxidant, the ideal structure of a phenolic compound was designed considering the factors that determine antioxidant potency. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran (BO-653) was thus synthesized and its antioxidant activity was evaluated against lipid peroxidationsin vitro.The electron spin resonance study showed that the phenoxyl radical derived from BO-653 was more stable than α-tocopheroxyl radical. BO-653 reduced α-tocopheroxyl radical rapidly, but α-tocopherol did not reduce the phenoxyl radical derived from BO-653. However, the chemical reactivity of BO-653 toward peroxyl radical was smaller than that of α-tocopherol. This was interpreted as the steric effect of bulkytert-butyl groups at bothorthopositions which hindered the access of peroxyl radical to the phenolic hydrogen. However, thetert-butyl substituents increased the stability of BO-653 radical and also lipophilicity, and its antioxidant potency against lipid peroxidation in phosphatidylcholine liposomal membranes was superior to that of α-tocopherol. Ascorbic acid reduced the phenoxyl radical derived from BO-653 and spared BO-653 during the oxidation of lipid in the homogeneous solution. On the other hand, ascorbic acid did not spare BO-653 in the oxidation of liposomal membranes. It was concluded that BO-653 is a potent novel radical-scavenging antioxidant.