Vitamin E model

Suarna, C. Southwell-Keely, P. T. Effects of alcohols on the oxidation of the vitamin E model compound 2,2,5,7 8-pentamethyl-6-chromanol. Lipids 1989, 24, 56-60. 

Matsumoto, S., Matsuo, M., litaka, Y. and Niki, E. (1986) Oxidation of a vitamin E model compound 2,2,5,7,8-pentamethylchroman-6-ol, with the rert-butylperoxy radical. J. Chem. Soc. Chem. Commun. 14 1076-1077. 

As soon as it was appreciated that oxygen toxicity was somehow involved in retrolental fibroplasia, antioxidant administration was empirically investigated in both animal models and babies. In 1949, Owens and Owens reported a protective effect of vitamin E unfortunately this could not be substantiated in subsequent controlled trials. Phelps and Rosenbaum (1977) investigated whether vitamin E supplementation would influence oxygen-induced retinopathy in kittens and found it to be beneficial in reducing the severity of the lesions. Nevertheless, vitamin E has not yet been used with much success in preterm babies. 

The oxidation of a-tocopherol (1) to dimers29,50 and trimers15,51 has been reported already in the early days of vitamin E chemistry, including standard procedures for near-quantitative preparation of these compounds. The formation generally proceeds via orf/zo-quinone methide 3 as the key intermediate. The dimerization of 3 into spiro dimer 9 is one of the most frequently occurring reactions in tocopherol chemistry, being almost ubiquitous as side reaction as soon as the o-QM 3 occurs as reaction intermediate. Early accounts proposed numerous incorrect structures,52 which found entry into review articles and thus survived in the literature until today.22 Also several different proposals as to the formation mechanisms of these compounds existed. Only recently, a consistent model of their formation pathways and interconversions as well as a complete NMR assignment of the different diastereomers was achieved.28... 

Skinner, W. A. Alaupovic, P. Oxidation products of vitamin E and its model, 6-hydroxy-2,2,5,7 8-pentamethyl-chroman. V. Studies of the products of alkaline ferricyanide oxidation. J. Org. Chem. 1963, 28, 2854—2858. 

Skinner, W. A. Parkhurst, R. M. Oxidation products of vitamin E and its model, 6-hydroxy-... 

Siler, U., L. Barella, V. Spitzer et al. 2004. Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model. Faseb J 18(9) 1019-1021. 

This method is also used to measure ex vivo low-density lipoprotein (LDL) oxidation. LDL is isolated fresh from blood samples, oxidation is initiated by Cu(II) or AAPH, and peroxidation of the lipid components is followed at 234 nm for conjugated dienes (Prior and others 2005). In this specific case the procedure can be used to assess the interaction of certain antioxidant compounds, such as vitamin E, carotenoids, and retinyl stearate, exerting a protective effect on LDL (Esterbauer and others 1989). Hence, Viana and others (1996) studied the in vitro antioxidative effects of an extract rich in flavonoids. Similarly, Pearson and others (1999) assessed the ability of compounds in apple juices and extracts from fresh apple to protect LDL. Wang and Goodman (1999) examined the antioxidant properties of 26 common dietary phenolic agents in an ex vivo LDL oxidation model. Salleh and others (2002) screened 12 edible plant extracts rich in polyphenols for their potential to inhibit oxidation of LDL in vitro. Gongalves and others (2004) observed that phenolic extracts from cherry inhibited LDL oxidation in vitro in a dose-dependent manner. Yildirin and others (2007) demonstrated that grapes inhibited oxidation of human LDL at a level comparable to wine. Coinu and others (2007) studied the antioxidant properties of extracts obtained from artichoke leaves and outer bracts measured on human oxidized LDL. Milde and others (2007) showed that many phenolics, as well as carotenoids, enhance resistance to LDL oxidation. 

It seems worthy to comment on the name second generation lazaroid. Fooking at the structure of U-83836E, one may wonder why this compound is associated with 12-amino steroids at all, whereas it is just another model of a-tocopherol and should be compared not with first generation lazaroids but with the synthetic analogs of vitamin E (see above). 

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