A-tocopherol hydroquinone

Fig. 5. Examples of GC-MS data for vitamin E in a vegetable oil and cattle feedlot soil (a) vegetable oil, sum of key ions mjz 129 (TMS for sterols), 474, 488 and 502 of tocopherols as TMS), (b) feedlot soil, sum of key ions ra/z 416 and 430 for tocopherols, a-tocopheryl acetate, and the metabolite (as free phenols), and (c) mass spectrum of a-tocopherol hydroquinone (V).

The propensity of 02 to remove protons from substrates accounts for its reactivity with acidic reductants and their overall oxidation. Thus, combination of 02 - with protic substrates (a-tocopherol, hydroquinone, 3,5-di-t-butylcatechol, L(- -)-ascorbic acid) yields products that are consistent with an apparent one-electron oxidation of the substrate and the production of HOOH. However, the results of electrochemical studies provide clear evidence that these substrates are not oxidized in aprotic media by direct one-electron transfer to 02. The primary step involves abstraction of a proton from the substrate by 02 to give substrate anion and the disproportionation products of HOO- (HOOH and O2). In turn, the substrate anion is oxidized by O2 in a multistep process to yield oxidation products and HOOH. Thus, by continuously purging the O2 that results from the... 

Studies of the metabolism of vitamin E were triggered by the observations of Alaupovic and coworkers [126, 127]. When " [Cj-D-a-tocopherol-5-methyl was administered to rats or pigs and attempts were made to detect metabolic derivatives, two compounds were separated by chromatography. One of the compounds is " [C]-D-a-tocopherol quinone the other is either a dimer or a trimer of a-tocopherol. The dimer and trimer are terminal oxidation products of a-tocopherol and are excreted in the bile. a-Tocopherol quinone can be converted to a-hydroquinone. a-Tocopherol hydroquinone may be esterified in liver and eliminated in the feces after concentration in the bile and excretion in the intestine, or it may be oxidized in the kidney to a-tocopheronic acid, which may be converted into an a-tocopheronolactone conjugate, which is excreted in the urine. In conclusion, vitamin E is excreted as such in the urine or the bile after conversion to a dimer or a trimer, in the form of a conjugated hydroxy-quinone or tocopheronic acid (see Fig. 4-43). 

Encouraged by the short synthesis of K vitamins, the chromium-mediated benzannulation was extended to the synthesis of vitamin E 68 [59]. The problem of imperfect regioselectivity of alkyne incorporation - which did not hamper the approach to vitamin K due to the final oxidation to the quinone - was tackled by demethylation of both regioisomeric hydroquinone monomethyl ethers 67 to give the unprotected hydroquinone. Subsequent ring closure yielded a-tocopherol (vitamin E) 68 (Scheme 39). 

The strong Bronstedt acid nature of some hexacoordinated phosphorus derivatives, [7",H ] (Et20)4 in particular, was recently used within the context of an industrial application [36]. The conjugated acid of tris(oxalato)phosphate anion 7 was found to effectively catalyze the ring-forming reaction of trimethyl-hydroquinone 63 with isophytol 64 to give (all rac)-a-tocopherol 65 (ethylene-carbonate/heptane 1 1,100 °C, 90%, Scheme 19). This process is particularly... 

FIGURE 6.13 a-Tocopherol-type benzofurans and benzopyrans having different strains in the alicyclic ring (15a-i) and nonanullated a-tocopherol-type hydroquinones (16a-b). 

A closely related and important family of chro-manols are the tocopherols or vitamins E (Fig. 15-24, Box 15-G). Tocopherols are plant products found primarily in plant oils and are essential to proper nutrition of humans and other animals. a-Tocopherol is the most abundant form of the vitamin E family smaller amounts of the P, 8, and y forms occur, as do a series of tocotrienols which contain unsaturated isoprenoid units.495 The configuration of a-tocopherol is 2R,4 R,8 R as indicated in Fig. 15-24. When a-toco-pherol is oxidized, e.g., with ferric chloride, the ring can be opened by hydrolysis to give tocopherolquinones (Fig. 15-24), which can in turn be reduced to tocopherol-hydroquinones. Large amounts of the tocopherolquinones have been found in chloroplasts. 

When a single hydrogen atom is removed from a hydroquinone or from a chromanol such as a tocopherol, a free radical is formed (Eq. 15-54). Phenols substituted in the 2,4, and 6 positions give especially stable radicals. 

Resveratrol has also been reported to offer protection against cardiovascular disease, such as coronary heart disease. The effects of resveratrol on factors implicated in the development of coronary heart disease - human platelet aggregation and the synthesis of eicosanoids (lipids) from arachidonate by platelets - were investigated and compared with the actions of other wine phenolics - catechin (1.39), epicatechin (7.18a), and quercetin (1.43) - and the antioxidants a-tocopherol (7.10a), hydroquinone and butylated hydroxytoluene. Resveratrol and quercetin demonstrated a dose-dependent inhibition of platelet aggregation, whereas the other compounds tested were inactive. Resveratrol also inhibited the synthesis of the eicosanoids in a dose-dependent manner, whereas the other phenolics were less effective of not effective at all. Removal of the alcohol from the wine did not diminish the effect on platelet aggregation (Pace-Asciak et al., 1995 Goldberg et al., 1995). 

Non-enzymatic RSH (eg, glutathione) Ascorbic acid (vitamin C) a-Tocopherol (vitamin E) P-Carotene Flavonoids Hydroquinones... 

In practice, a-tocopherol (rac-1) is industrially produced on a large scale by an acid-catalyzed reaction of trimethyl hydroquinone (3) with all-rac-isophytol (4) as a mixture of all eight possible stereoisomers." ... 

Biochemical Function. The best way to describe tocopherol s role is that of a lipid-soluble antioxidant. It protects unsaturated lipids from o gen-induced peroxide formation. There Is evidence for both free-radical one-electron chemistry (Fig. 8.20) and two-electron qui-none-hydroquinone chemistry (Fig. 8.21) (35). The oxidized/reduced glutathione system may he part of the system that regenerates reduced a-tocopherol. At one time it was thought that the preference for the 2-R stereoisomers indicated that the vitamin was part of a biochemical oaddation/reduction system, possibly as a coenzyme. So far that role for a-tocopherol has not been found. The current evidence points to the... 

Phytol, CAS no. [150-86-7] C20H40O, an alcohol obtained by the decomposition of chlorophyll is an odorless liquid, BP 202—204°C/10mm Hg and has been used in the synthesis of vitamin E. On reaction with trimethyl hydroquinone phytol is converted to a-tocopherol, etc. 

Two examples of radical inhibitors that are present in biological systems are vitamin C and vitamin E. Like hydroquinone, they form relatively stable radicals. Vitamin C (also called ascorbic acid) is a water-soluble compound that traps radicals formed in the aqueous environment of the cell and in blood plasma. Vitamin E (also called a-tocopherol) is a water-insoluble (hence fat-soluble) compound that traps radicals formed in nonpolar membranes. Why one vitamin functions in aqueous environments and the other in nonaqueous environments should be apparent from their structures and electrostatic potential maps, which show that vitamin C is a relatively polar compound, whereas vitamin E is nonpolar. 

Thus, the aldol shown, which is susceptible to Sharpless-type epoxidation, has been obtained from phytal and the protected hydroquinone (ref. 120). Formation of the epoxide presumably with a chiral peracid (or perhaps with a conventional peracid relying on the asymmetry of the substrate) and then cleavage reductively in t-butyl methyl ketone containing lithium aluminium hydride led to a diol. The benzylic hydroxyl group of this was hydrogenolysed to afford the hydroquinone dimethyl ether in 85% yield. Ceric ammonium nitrate (CAN) oxidation afforded the intermediate benzoquinone hydrogenation of which was reported to result in 2R,4 R,8 R-a-tocopherol by, presumably, avoidance of a racemisation step. 

The optically active chroman unit (1050) of a-tocopherol (vitamin E) (1051) is constructed by an initial coupling reaction between aldehyde 1032 and the hydroquinone Grignard reagent... 

The tocopherols are converted by oxidation to tocopheryl quinones, which upon reduction become tocopheryl hydroquinones. The reduction of a-tocopheryl quinone to a-tocopheryl hydroquinone occurs either via NADPH-cytochrome P45Q reductase, NAD(P)H quinone oxidoreductase 1, or ascorbate for the other tocopherols these pathways have not been tested. The tocophrayl hydroquinones can regenerate the toeopheroxyl radical and thus preserve a-tocophraol with different effieieneies (a > p > y-toeopheryl hydroquinone). ... 

Erhard Fernholz was the first to demonstrate the relationship of vitamin E to duro-hydroquinone by isolating that substance from the pyrolysis products of a-tocopherol. In a masterly degradation study (1937,1938), he proposed that a-tocopherol could be represented by the structural formula we now know it to possess. In the untimely death of this young genius, science lost a chemist of outstanding ability. 

Todd independently isolated /3-tocopherol from w hcat germ oil, showed that on pyrolysis it yielded trimethyl hydroquinone, and independently synthesized a-tocopherol by condensing phytol with trimethyl hydroquinone he synthesized the three dimethyl toeopherols by condensing phytol with the three dimethyl hydroquinones (Bcrgel et al., 19.38). He also synthesized some cjhromans and coumarans by unambiguous methods and showed that they closely resembled the natural tocopherol. 

Golumbic, C., and Mattill, H. A. 1941. Antioxidants and the antoxidation of fats. XIII. The antioxygenic action of ascorbic acid in association with tocopherols, hydroquinones and related compounds. J. Am. Chem. Soc. 63, 1279. 

Under the proper conditions, a chromane is obtained, as indicated in the figure, and the synthetic compound has biological properties identical to that of the natural vitamin. Once the structure of a-tocopherol was established, the structures of jS-, 7-, and 5-tocopherol were soon elucidated. The degradation products were identical in all cases, with the exception of the substituted hydroquinone. The y- and 5-isomers were shown to have the substitution illustrated in Fig. 4-40. Later, the and j8-tocopherols were purified by two-dimensional chromatography. 

Standards a-, P-, y-, and 8-Tocopherols, tocopherol quinones, tocopherol hydroquinones TMS derivatives GC-MS Rtx-5MS column, temperature 220-290°C 0-15 ng tocopherols 40 pg/pL for all tocopherols Melchert et al. (2002)... 

Structure of a-tocopherol.— Femholtz has shown that the vitamin is a cyclic ether of hydroquinone, and suggested that it is a derivative of the chromane nucleus. This has been confirmed by synthesis (Smith, Karrer) and biological, assay of synthetic chromanes (Evans and Emerson), and it has been shovm that the vitamin is a chromane with two substituents, and that other ethers of hydroquinone display vitamin E activity when fed at high levels. 

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