Tocopherol reaction product

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). 

A. N. Wijewickreme and D. D. Kitts, Oxidative reactions of model Maillard reaction products and a-tocopherol in a flour-lipid mixture, J. FoodSci., 1998, 63, 466-471. 

In accordance with168, a-tocopherol CXXTV which is a biological antioxidant acts by a combination of chemical reaction and physical quenching. The relatively unstable hydroperoxycyclohexadienone CXXV is formed first in its reaction with 102 and the final reaction products a-tocopheroquinone CXXVI and a-toco-pheroquinonepoxide CXXVII arise by its further transformation. 

A long-standing and fundamental problem that has frustrated attempts to directly demonstrate free radical-mediated toxicity relates to the inability to verify various reaction products seen in vivo as being derived from specific radical species. The ability of various antioxidants, such as ascorbate, tocopherol, glutathione, and cysteine, to limit or prevent injury in various models is suggestive of oxidative pathology but offers little with regard to... 

The final resistance mechanism to be discussed is related more directly to the proposed mechanism of action of the newer DPE s, Tissue allowed to green for 48 h before herbicide treatment may have increased levels of vivo free radical scavengers (e.g., tocopherols) that are able to quench the light-activated form of the DPE molecule or subsequent reaction products (15). This resistance mechanism might be overcome by destroying the a-tocopherol (ot-T) present with picrylhydrazyl... 

Utsunomiya, N. Hayase, F. Kato, H. Antioxidative activities of Maillard reaction products of D-glucose with ovalbumin hydrolyzed by proteases, and their synergistic effect with tocopherols. Nippon Eiyo Shokuryo Gakkaishi. 1983, 36, 461-465. 

Strohecker [97] has worked out a procedure for quantitative determination of ascorbyl palmitate in oils and fats he oxidises with 2,6-dichlorophenol-indophenol and treats the reaction product with 2,4-dinitrophenylhydrazine. The 2,4-dinitroosazone of ascorbic acid is formed under these conditions and may be easily separated from other compounds containing phenolic groups such as tocopherols. He uses a silica gel H layer and chloroform-ethyl acetate (50 + 50) for TLC. After development, the brick red zone of the osazone is scraped off and determined colorimetrically in solution m sulphuric acid. Down to 0.001% of ascorbyl palmitate in antioxidant mixtures and in oils and fats can be determined with this procedure. 

R Yamauchi, T Matsui, K Kato, Y Ueno. Reaction products of a-tocopherol with methyl linoleate-peroxyl radicals. Lipids 25 152-158, 1990. 

O-alkyl- a-tocopherol Figure 5.7 Main reaction products of a-tocopherol with oxidised lipids. 

Similarly to a-tocopherol, other tocopherols and tocotrienols also react with oxidised lipids Some reaction products of y-tocopherol, such as tocopherol red (tocored, 5-40, arising during... 

Rishi et al. (2011) have reported two different Fl-spectrophotometric methods for a-tocopherol determination in pharmaceuticals and infant milk powder. Method I, was based on the reduction of iron(III) to iron(II) in the presence of vitamin E, and reaction between iron(II) and 1,10-phenanthroline formed iron(II)-o-phenanthroline red complex with maximum wavelength of 510 nm. Method II was based on previously reported work (Prieto et al., 1999) involving the reduction of Mo(VI) to Mo(V) by vitamin E and the subsequent formation of a green phosphate/Mo(V) complex in aqueous sulfuric acid monitored at 695 nm. Triton X-100 was used as a sample carrier for solubility of vitamin E and for removal of the deposits of reaction product on the glass flow-through cell to achieve maximum peak height absorbance. The temperature of reaction coil I was kept at 85 1 C and that of coil II at 20 1°C. 

Al-Malaika, S., Issenhuth, S. The antioxidant role of vitamin E in polymtas. IV. Reaction products of dl-oi-tocopherol with lead dioxide and with polyolefins. Polymta 42(7), 2915-2939 (2001)... 

As Table 6.3 shows, all partly hydroxylated aluminum fluoride samples (note that numbers associated with the hydroxylated aluminum fluoride represent the concentration of aqueous HE used in sol-gel synthesis) are very active catalysts (e.g., the conversion of IP reaches 100% in only 1 h of reaction) but the distribution of the reaction products is different as a function of the Lewis/Brpnsted acid site ratio. Therefore, for a ratio of TMHQ/IP = 1/1 (Table 6.3, entries 1-5) the yield of (all-rac)-a-tocopherol decreases in the following order ... 

In opposition, employing HS-AIF3 (pure Lewis acid) as catalyst, the conversion of IP reached only 70% and no (all-rac)-a-tocopherol was identified (Table 6.3, entry 1) in reaction products. Contrarily, besides phytadiene, other by-products known from literature [101] or not claimed until now (i.e., quinone) were identified, even though only in small amounts [78]. 

The carbanions of 1-alkenyl sulphoxides 400 also react with carbonyl compounds to give the corresponding condensation products (equation 237). Solladie and Moine have used this type of reaction in their enantiospecific synthesis of the chroman ring of a-tocopherol 401. Addition of the lithio reagent 402 to the aldehyde 403 affords the allylic alcohol 404 in 75% yield as a sole diastereoisomer (equation 238). 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

Chromanoxylium cation 4 preferably adds nucleophiles in 8a-position producing 8a-substituted tocopherones 6, similar in structure to those obtained by radical recombination between C-8a of chromanoxyl 2 and coreacting radicals (Fig. 6.4). Addition of a hydroxyl ion to 4, for instance, results in a 8a-hydroxy-tocopherone, which in a subsequent step gives the /zara-tocopherylquinone (7), the main (and in most cases, the only) product of two-electron oxidation of tocopherol in aqueous media. A second interesting reaction of chromanoxylium cation 4 is the loss of aproton at C-5a, producing the o-QM 3. This reaction is mostly carried out starting from tocopherones 6 or /zora-tocopherylquinone (7) under acidic catalysis, so that chromanoxylium 4 is produced in the first step, followed by proton elimination from C-5a. In the overall reaction of a tocopherone 6, a [ 1,4] -elimination has occurred. The central species in the oxidation chemistry of a-tocopherol is the o-QM 3, which is discussed in detail subsequently. 

FIGURE 6.4 Reactions and products of the primary oxidation intermediates of a-tocopherol (1), the tocopheroxyl radical 2, ortho-quinone methide 3, and chromanoxylium cation 4. 

The third fact that seemed to argue in favor of the occurrence of radicals 10 was the observation that reactions of a-tocopherol under typical radical conditions, that is, at the presence of radical initiators in inert solvents or under irradiation, provided also large amounts of two-electron oxidation products such as o-QM 3 and its spiro dimerization product 9 (Fig. 6.8).16,25,26 This was taken as support of a disproportionation reaction involving a-tocopheroxyl radical 2 and its hypothetical tautomeric chromanol methide radical 10, affording one molecule of o-QM 3 (oxidation) and regenerating one molecule of 1 (reduction). The term disproportionation was used here to describe a one-electron redox process with concomitant transfer of a proton, that is, basically a H-atom transfer from hypothetical 10 to radical 2. 

To conclusively disprove the involvement of the chromanol methide radical, the reaction of a-tocopherol with dibenzoyl peroxide was conducted in the presence of a large excess of ethyl vinyl ether used as a solvent component. If 5a-a-tocopheryl benzoate (11) was formed homolytically according to Fig. 6.6, the presence of ethyl vinyl ether should have no large influence on the product distribution. However, if (11) was formed heterolytically according to Fig. 6.9, the intermediate o-QM 3 would be readily trapped by ethyl vinyl ether in a hetero-Diels-Alder process with inverse electron demand,27 thus drastically reducing the amount of 11 formed. Exactly the latter outcome was observed experimentally. In fact, using a 10-fold excess of ethyl vinyl ether relative to a-tocopherol and azobis(isobutyronitrile) (AIBN) as radical... 

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