Α-tocopherol Model Compound Research Articles

In vitro radical-scavenging mechanism of melatonin and its in vivo protective effect against radiation-induced lipid peroxidation

Melatonin (N-acetyl-5-methoxytryptamine, MLT), an evolutionarily conserved indoleamine, is known to act as an antioxidant. However, the evidence indicating the role of MLT as a powerful chain-breaking antioxidant by scavenging peroxyl radical remains controversial. The radical-scavenging rate of MLT determined in this study in methanol using galvinoxyl radical (GO•) was much lower than that of an α-tocopherol model compound. The acceleration of the GO•-scavenging reaction by MLT was observed in the presence of magnesium ion (Mg2+), a bio-related redox-inactive metal ion, suggesting that this reaction may proceed via a rate-determining electron transfer followed by proton transfer. The coordination of Mg2+ to the carbonyl oxygen in the one-electron reduced species of GO• (GO–) may stabilize the product, resulting in the acceleration of the electron-transfer process. We also demonstrated that prophylactically administrated MLT efficiently inhibited the lipid peroxide-derived protein modification, which can be detected by a sensitive marker, Nε-(hexanoyl)lysine adduct, in the plasma of X-irradiated mice. The relatively weak GO•-scavenging activity of MLT suggests that the ameliorative effect of MLT against in vivo lipid peroxidation does not result from the direct scavenging of lipid peroxyl radicals by MLT. Therefore, the observed superior protective efficiency of MLT against in vivo lipid peroxidation may partly support the earlier studies, which reported the synergistic antioxidative effect of the metabolites of MLT.

Stabilization of ortho-quinone methides by a bis(sulfonium ylide) derived from 2,5-dihydroxy-[1,4]benzoquinone

The zwitterionic intermediates ( 2a) in the oxidation of ortho-alkylphenols ( 1) and bis(sulfonium ylide) 3 form reasonably stable 2:1-complexes ( 4), in which the ortho-quinone methide ( oQM) moieties are not present in quinoid form with the exocyclic in-plane methylene group, but as zwitterionic, aromatic conformer having an out-of-plane exocyclic methylene group. The complex 7 derived from the α-tocopherol model compound PMC ( 5) was comprehensively characterized. As exemplarily demonstrated, the adducts can be advantageously employed in organic synthesis as ‘stabilized oQMs’.

Reaction of 2,2,5,7,8-pentamethyl-6-chromanol, an α-tocopherol analogue, with NO in the presence of oxygen

An α-tocopherol model compound, 2,2,5,7,8-pentamethyl-6-chromanol, reacted with nitric oxide (NO) in the presence of various amounts of oxygen to afford four major products. Distribution of the products was varied depending on the ratio of NO and O 2, and the preincubation time of NO and O 2.

Hydroxyl radical formation from Cu(II)-trolox mixtures: insights into the pro-oxidant properties of α-tocopherol

Although widely recognised as the most important chain-breaking antioxidant of the lipid phase, α-tocopherol has also been reported to exert pro-oxidant activity, particularly during the Cu(II)-stimulated oxidation of low density lipoproteins (LDL). In the present communication, we demonstrate that hydroxyl radicals are generated following the interaction of Cu(II) with the α-tocopherol model compound Trolox, involving the reduction of Cu(II) by Trolox and the subsequent reduction of molecular oxygen by Cu(I). We suggest, therefore, that the hydroxyl radical may be the species responsible for the initiation of fatty acid oxidation during the Cu(II)-stimulated oxidation of hydroperoxide-free LDL.

Separation of the α-Tocopherol Model Compound 2,2,5,7,8-Pentamethyl-6-Chromanol from its Oxidation Products by High Performance Liquid Chromatography

Abstract A rapid method is described for the separation of the α-tocopherol model compound, 2,2,5,7,8-pentamethyl-6-chromanol (6), from 9 of its oxidation products in a single 35 minute run. Separated derivatives of 6, in order of elution, included the 5-cholesteroxymethyl (1), spirotrimer (2), spirodimer (3), 5-formyl (4), 5-ethoxymethyl (5), dihydroxydimer (7), chroman dione (8), quinone (9) and pyrano xanthene (10). A normal phase system, using gradient elution is employed, the eluent being monitored at 290 nm. The minimum detection limit for compounds 1–8 was 0.1 μg per injection and for compounds 9 and 10 it was 0.3 μg per injection.

Free radicals of tocopherol model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman which are produced from the reaction with superoxide ion, [formula omitted]: studies by high-performance liquid chromatography

Reaction of superoxide ion, O 2 − , with α-tocopherol model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman ( ▪), was investigated by high-performance liquid chromatography (HPLC). Chromatogram of the reaction mixture showed three peaks with retention times of 2.5, 1.8 and 1.5 min, and each peak height was dependent on the concentration of O 2 − . Chemical species having the retention time of 1.5 min was ascribed to chromanoxyl radical ( ▪), and the other chemical species having the retention times of 2.5 and 1.8 min were identified with the model compound ( ▪) and 2-hydroxy-2-methyl-4-(3, 5, 6-tri-methylbenzoquinone-2-yl)butane ( ▪), respectively. This is a first evidence that the free radicals from tocopherol model compounds was separated by HPLC.

Spectroscopic studies on the reaction of superoxide ion with tocopherol model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman

The reaction of superoxide ion, O 2 − , with α-tocopherol model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman ( lb ), was investigated spectrophotometrically in acetonitirle. The transient absorption (λmax=330 nm) observed at the initial stage of the reaction was ascribed to the chromanoxyl-type radical, one-elecron oxidation product of compound lb , on the basis of the spectroscopic [ultraviolet(UV)/visible and electron spin resonance (ESR)] data. Further, the final product observed was ascribable to the tocopherol quinone ( 3 ).

ChemInform Abstract: THE REVISED STRUCTURE OF AN OXIDATION PRODUCT FROM THE REACTION OF AN α‐TOCOPHEROL MODEL COMPOUND, 2,2,5,7,8‐PENTAMETHYLCHROMAN‐6‐OL, WITH POTASSIUM SUPEROXIDE; 6‐HYDROXY‐2,2,6,7,8‐PENTAMETHYLCHROMAN‐5(6H)‐ONE

Chemischer InformationsdienstVolume 13, Issue 4 Heterocyclic Compounds ChemInform Abstract: THE REVISED STRUCTURE OF AN OXIDATION PRODUCT FROM THE REACTION OF AN α-TOCOPHEROL MODEL COMPOUND, 2,2,5,7,8-PENTAMETHYLCHROMAN-6-OL, WITH POTASSIUM SUPEROXIDE; 6-HYDROXY-2,2,6,7,8-PENTAMETHYLCHROMAN-5(6H)-ONE S. MATSUMOTO, S. MATSUMOTOSearch for more papers by this authorM. MATSUO, M. MATSUOSearch for more papers by this authorY. IITAKA, Y. IITAKASearch for more papers by this author S. MATSUMOTO, S. MATSUMOTOSearch for more papers by this authorM. MATSUO, M. MATSUOSearch for more papers by this authorY. IITAKA, Y. IITAKASearch for more papers by this author First published: January 26, 1982 https://doi.org/10.1002/chin.198204225Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume13, Issue4January 26, 1982 RelatedInformation

The revised structure of an oxidation product from the reaction of an α-tocopherol model compound, 2,2,5,7,8-pentamethylchroman-6-ol, with potassium superoxide; 6 -hydroxy -2,2,6,7,8- pentamethylchroman- 5 (6H) -one 1

The previously reported structure of an oxidation product obtained from the reaction of an (α-tocopherol model compound(1) with KO 2 is revised to 6-hydroxy-2,2,6,7,8-pentamethylchroman-5(6H)-one(3) on the basis of the X-ray crystallographic and 18O-labeling studies.

Potassium t-butoxide-catalysed oxygenation of an α-tocopherol model compund 2,2,5,7,8-pentamethylchroman-6-ol

The potassium t-butoxide-catalysed oxygenation of an α-tocopherol model compound, 2,2,5,7,8-penta-methylchroman-6-ol, gave 5-hydroxy-2,2,5,7,8-penta-methylchroman-6(5H)-one (2) and 7,8-dihydro-5,7-dihydroxy-8-methylene-2,2,5,7-tetramethychroman-6(5H)-one, and 6-hydroxy-2,2,6,7,8-pentamethylchroman-5(6H)- one which was found to be formed as the result of the acyloin rearrangement of (2).

ChemInform Abstract: EPOXIDATION OF AN α‐TOCOPHEROL MODEL COMPOUND, 2,2,5,7,8‐PENTAMETHYLCHROMAN‐6‐OL, WITH POTASSIUM SUPEROXIDE; X‐RAY CRYSTAL STRUCTURE OF 4A,5;7,8‐DIEPOXY‐4A,7,8,8A‐TETRAHYDRO‐8A‐HYDROXY‐2,2,5,7,8‐PENTAMETHYLCHROMAN‐6(5H)‐ONE

AbstractIn Gegenwart von Dieyclohexyl‐ 18]krone‐6 wird das Chromanol (I) unter Sauerstoff mit Kaliumperoxid zum Diepoxid oxidiert.

Epoxidation of an α-tocopherol model compound, 2,2,5,7,8-pentamethylchroman-6-ol, with potassium superoxide; X-ray crystal structure of 4a,5;7,8-diepoxy-4a,7,8,8a-tetrahydro-8a-hydroxy-2,2,5,7,8-pentamethylchroman-6(5H)-one

An α-tocopherol model compound, 2,2,5,7,8-pentamethylchroman-6-ol, was oxidized in the presence of dicyclohexyl-18-crown-6 with KO2 to give a diepoxide, whose structure was determined by spectroscopy and X-ray crystallography.

The reaction of a α-tocopherol model compound with KO 2, a new oxidation product of 6-hydroxy-2,2,5,7,8-pentamethylchroman

The reaction of a α-tocopherol model compound with KO 2, a new oxidation product of 6-hydroxy-2,2,5,7,8-pentamethylchroman

Oxidation of α-tocopherol model compound by superoxide anion

6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a model for α-tocopherol, was found to be oxidized by a xanthine-xanthine oxidase system. This reaction was found to be completely inhibited by the addition of superoxide dismutase, while catalase had no effect, indicating that the oxidation is caused by superoxide anion. The product of the oxidation was identified as 2-hydroxy-2-methyl-4-(3,4,6-trimethylbenzoquinone-2-yl) butanoic acid. An intermediate, which has properties of 8a-hydroxy-2,5,7,8-tetramethyl-chroman-6-one-2-carboxylic acid, was observed spectrophotometrically prior to the formation of the quinone. From an analysis of the inhibition of the rate of reaction by superoxide dismutase, the second-order rate constant for the reaction between 6-hydroxy-2, 5,7,8-tetramethylchroman-2-carboxylic acid and superoxide anion was estimated to be 1.7 × 10 4 m −1 s −1. This value is fairly small compared to the second-order rate constant for the reaction between superoxide dismutase and superoxide anion. However, in view of the localization of α-tocopherol in subcellular membranes, it seems possible that this vitamin scavenges the superoxide anion which may be generated by membrane-bound enzymes participating in the biological oxidation.

Studies on the Oxidation Mechanism of Vitamin E

α-Tocopherol model compound, 2,2,5,7,8-pentamethyl-6-hydroxychroman was oxidized under oxygen bubbling. Four oxidation products of 2-(γ,γ-dimethylallyl)-3,5,6-trimethyl-1,4-benzoquinone (B), 2,2,7,8-tetramethyl-5-formyl-6-hydroxychroman (C), trimer (D) and tocopherylethane (G) were identified, and spirodimer (E) was tentatively identified by TLC. Two of them, (B) and (C) have not been obtained in the oxidation of α-tocopherol model compound with p-quinone, alkaline ferricyanide and other compounds as oxidizing agent. A scheme of oxidation mechanism of α-tocopherol model compound was also proposed.