Tocopherols analog

Different methods have been used for determination of antioxidant activity. Rice-Evans et al. (1997) have used a method based on the ability to quench the colored ABTS radicals to compare antioxidant activity of some carotenoids. The results were calculated as the Trolox equivalent of antioxidant capacity (TEAC). The activity of Trolox, the water soluble a-tocopherol analog, was given a value of 1. A higher value in this assay indicated a higher activity of the carotenoid (Table 9.3). 

The selectivity of higher organisms for a-tocopherol has been impressively demonstrated in recent years by analysing the metabolism of vitamin E. Excess a-tocopherol and the other tocopherol analogs are extensively metabolized before excretion. This finding suggests that the organism maintains the correct vitamin E level by selective retention of a-tocopherol, and by specific metabolism of all the other tocopherols and of the excess a-tocopherol. Keep in mind that the tocopherol metabolites can also act as bioactive compounds, which can bind to... 

In this chapter, an attempt will be made to highlight the new trends in this area. The approach that was chosen is to briefly summarize the state of the art before 1989, based on the chapters on vitamin E in the two previous editions of this book and an earlier review paper (25-27) and to confront this with the new developments since then. Sections II through V are only concerned with vitamin E sensu strictu—i.e., tocopherols and tocotrienols. The chromatography of stereoisomers, oxidation products, metabolites, and tocopherol analogs is treated separately in sections VI.A through VI.C. 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

The methano-dimer of a-tocopherol (28)50 was formed by the reaction of o-QM 3 as an alkylating agent toward excess y-tocopherol. It is also the reduction product of the furano-spiro dimer 29, which by analogy to spiro dimer 9 occurred as two interconvertible diastereomers,28 see Fig. 6.23. However, the interconversion rate was found to be slower than in the case of spiro dimer 9. While the reduction of furano-spiro dimer 29 to methano-dimer 28 proceeded largely quantitatively and independently of the reductant, the products of the reverse reaction, oxidation of 28 to 29, depended on oxidant and reaction conditions, so that those two compounds do not constitute a reversible redox pair in contrast to 9 and 12. 

Treatment of methano-dimer 28 with elemental bromine revealed a remarkable reactivity at low temperatures it proceeded quantitatively to the furano-spiro dimer 29, by analogy with the ethano-dimer 12 giving spiro dimer 9 upon oxidation. With increasing temperatures, the reaction mechanism changed, however, now affording a mixture of 5-bromo-y-tocopherol (30) and spiro dimer 9 (Fig. 6.24). Thus, the methano-dimer 28 fragmented into an a-tocopherol part, in the form of o-QM 3 that dimerized into 9, and a /-tocopherol part, which was present as the 5-bromo derivative 30 after the reaction. Thus, the overall reaction can be regarded as oxidative dealkylation. 

FIGURE 6.37 Synthesis of 3-(5-tocopheryl)-propionic acid (50) by trapping the intermediate ortho-QM 3 with a ketene acetal. Reaction products of 50 are formed in complete analogy to a-tocopherol (1). 

FIGURE 6.44 Oxidation of 3-oxa-chromanol 67, having no protons at position C-4a able to undergo rearrangements by analogy to 3-oxa-chromanol 59 with its oxidation intermediates 63 and 64. Due to this blocking at C-4/C-4a, the oxidation behavior of 67 resembles that of a-tocopherol (1). 

FIGURE 6.45 Inability of 5a-substituted derivatives to form structures analogous to o-QM 3 causes increased oxidative stability as in compounds 71 and 72. 5-(p-Hydroxyphenyl)-y-tocopherol (73) is oxidized to the conjugatively stabilized o-QM 74, the phenylogous a-tocored (75). 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

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). 

The correlation between the TEARS assay and MDA dnring oxidation of edible oils may be complicated by the presence of tocopherols (e.g. Vitamin E, 21) . An evaluation was carried of MDA, determined by an independent method , and TEARS as indices for direct oxygen uptake of edible oils and unsatnrated fatty acids. The linear increase of MDA and TEARS with oxygen consumption of soybean oil, in a closed vessel at 170 °C, stops when the latter value reaches 500 p.molL, when both MDA and TEARS start to decrease on further O2 consumption. The same process carried out at 40 °C, using 2,2 -azobis(2,4-dimethylvaleronitrile) (171) as initiator, shows linearity up to 1500 p,molL O2 consumption . A similar behavior is observed for nnsatnrated fatty acids snch as oleic, linoleic and linolenic acids . On the other hand, depletion of Vitamin E (a-tocopherol, 21) and its analogs y- and 5-tocopherol (172, 173) present in the oil show a linear dependence on O2 consumption of the oil, np to 1800 p,molL . This points to the consumption of these antioxidants, and especially 21, as a good index for the O2 uptake in oils at high temperature. The determination of the tocopherols is carried ont by HPLC-FLD (Xex = 295 nm, Ah = 325 nm) . ... 

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