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 peroxidations in vitro. The electron spin resonance study showed that the phenoxyl radical derived from BO-653 was more stable than alpha-tocopheroxyl radical. BO-653 reduced alpha-tocopheroxyl radical rapidly, but alpha-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 alpha-tocopherol. This was interpreted as the steric effect of bulky tert-butyl groups at both ortho positions which hindered the access of peroxyl radical to the phenolic hydrogen. However, the tertbutyl 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 alpha-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.
Noguchi
N
N
Research Center for Advanced Science and Technology, University of Tokyo, Japan.
Iwaki
Y
Y
Takahashi
M
M
Komuro
E
E
Kato
Y
Y
Tamura
K
K
Cynshi
O
O
Kodama
T
T
Niki
E
E
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D001391:Azo Compounds / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000378:metabolism; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008041:Linoleic Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000378:metabolism; D015394:Molecular Structure; D009570:Nitriles / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D013113:Spin Labels; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001391:Azo Compounds; D001559:Benzhydryl Compounds; D001572:Benzofurans; D016166:Free Radical Scavengers; D008041:Linoleic Acids; D008081:Liposomes; D009570:Nitriles; D010545:Peroxides; D010636:Phenols; D010713:Phosphatidylcholines; D013113:Spin Labels; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D014810:Vitamin E; C005575:methyl linoleate; C049375:perhydroxyl radical; D001205:Ascorbic Acid; C020338:galvinoxyl