Tocopherol synthetic

To address the question of whether the biological antioxidant would withstand the high melt processing temperatures, dl-a-tocopherol (synthetic vitamin E) was extruded at different concentrations in PE and PP under different processing temperatures ranging from 210 °C to 285 °C. Similar experi-... 

Vitamin E-deficient female animals suffer death and resorption of the fetuses. This was the basis of the original biological assay of the vitamin female rats were maintained for 2 to 3 months on a vitamin E-free diet and then mated. Impregnation and implantation proceed normally but, if they are not provided with vitamin E, the fetuses die and are resorbed. Five days after mating, the animals were killed, and the number of surviving fetuses gave an index of the biological activity of the test compound, relative to standard doses of a-tocopherol. Synthetic antioxidants can replace vitamin E for this function, but selenium cannot. 

While there is no universally accepted scientific terminology for representation there is general agreement on a certain working nomenclature (refs. 97,98). Thus a-tocopherol, the natural stereoisomer is as stated earlier (RRR)-a-tocopherol, the 2-epimer is 2-epi-a-tocopherol and a mixture of (RRR) and (SRR)-a-tocopherols is 2-ambo-a-tocopherol. Synthetic a-tocopherol prepared from synthetic phytol or isophytol is called all-rac-a-tocopherol, since it is theoretically a mixture of (RRR) and (SSS). The mixture of reduction products of 5,7,8-trimethyltocotrienol is called 4 -ambo-8 -ambo-a-tocopherol since as a natural product, although it has a 2R centre, the stereochemistry from hydrogen addition at the 4- and 8- positions is probably substantially RS. 

Vitamin E is the most important lipid-soluble antioxidant in biological systems. (all-rac)-a-Tocopherol (synthetic vitamin E, 1) is the economically most important product industrially prepared on a multi-10 OOOt/year scale and mainly used in animal nutrition [50]. In the large-scale syntheses of 1, 2,3>5-trimethylhydroquinone (6) is used as the aromatic key building block, which is condensed with isophytol (2) to yield 1 by all producers worldwide (Scheme 7.1). Trimethylhydroquinone (TMHQ, 6), in turn, is obtained from trimethylquinone (TMQ, 5) by reduction procedures, in particular catalytic hydrogenation. Besides other possibilities to access TMHQ (6), this route is generally preferred, and efficient oxidation processes for the production of quinone 5 from alkylated phenols are, therefore, of high interest [51]. 

Commercially available vitamin E consists of either a mixture of namrally occurring tocopherols and tocotriraiols (from natural sources), RRR-a-tocopherol (formerly called d-a-tocopherol), synthetic a-tocopherol, consisting of the eight possible side-chain stereoisomers at eqnal amonnts (all roc-a-tocopherol, formerly called dl-a-tocopherol), or their esters (a-tocophrayl succinate, a-tocopheryl acetate, a-toco-... 

O-Paimitoyi-L-ascorbic acid (ascorbyi palmitate) Extracts of naturai origin rich in tocopherols Synthetic a-tocopheroi Synthetic y-tocopheroi Synthetic <5-tocopheroi... 

Synthetic a-tocopherol exhibits, unKke natural a-tocopherol, lower biological activity, because it consists of the C-2 enantiomers, (2J )-a-tocopherol and (2S)-a-tocopherol. In short, synthetic a-tocopherol is (2J S)-a-tocopherol (D,L-a-tocopherol or 2-ambo-a-tocopherol). Synthetic a-tocopherol can also be a racemic mixture of all possible stereoisomers and it then consists of (2RS)-, (A RS)-and (8 J S)-a-tocopherol (or 2-ambo-, A -ambo and 8 -ambo-a-tocopherol), which is called all-rac-a-tocopherol. 

Gruppo Italiano per lo 11 324 survivors of Ml within a-tocopherol (synthetic) Nonsignificant decrease (11%) in Marchioli R (1999)... 

Primary Prevention 4495 subjects with > 1 major a-tocopherol (synthetic) Vitamin E had no significant effect on Primary Prevention... 

Antioxidants (qv) have a positive effect on oils when present in the proper concentration. Sterols and tocopherols, which are natural antioxidants, may be analy2ed by gas-Hquid chromatography (glc), high performance Hquid chromatography (hplc), or thin-layer chromatography (tic). Synthetic antioxidants maybe added by processors to improve the performance or shelf life of products. These compounds include butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), / fZ-butyUiydroquinone (TBHQ), and propyl gallate. These materials may likewise be analy2ed by glc, hplc, or tic. Citric acid (qv), which functions as a metal chelator, may also be deterrnined by glc. 

The most popular natural antioxidants on the market are rosemary extracts and tocopherols. Natural antioxidants have several drawbacks which limit use. Tocopherols are not as effective ia vegetable fats and oils as they are ia animal fats. Herb extracts often impart undesirable colors or flavors ia the products where used. In addition, natural antioxidants cost considerably more than synthetic ones. Despite this, the pubHc s uncertainty of the safety of synthetic antioxidants continues to fuel the demand for natural ones (21). 

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

No unequivocal unique function for vitamin E has been defined. However, it does act as a hpid-soluble antioxidant in cell membranes, where many of its functions can be provided by synthetic antioxidants. Vitamin E is the generic descriptor for two famihes of compounds, the tocopherols and the tocotrienols (Figure 45—5). The different vitamers (compounds having similar vitamin activity) have different biologic potencies the most active is D-a-tocopherol, and it is usual to express vitamin E intake in milhgrams of D-a-tocoph-erol equivalents. Synthetic DL-a-tocopherol does not have the same biologic potency as the namrally occurring compound. 

The most common natural antioxidants are tocopherols, ascorbic acid and P-carotene (more often synthetic nature-identical compounds than natural products). Their changes were studied in detail in model systems, fats and oils, but experimental evidence is mainly lacking on more complicated systems, such as natural foods and ready dishes. Still less is known on different antioxidants from spices and from essential oils. These data will probably be obtained gradually. Very little is known about synergism of antioxidants in food products other than edible fats and oils or their regeneration from the respective free radicals and quinones. In mixtures, some antioxidants are preferentially destroyed and others are saved. Some data have already been published, but these complex changes should be studied in more detail. 

Among the plant phenols, the flavonoids and the anthocyanidins, belonging to the 1,3-diphenylpropans, have been studied in most detail, mainly because of their potential health benefits. With more than 4,000 different flavonoids known, systematic studies of the effects of variation in molecular structure on physico-chemical properties of importance for antioxidative effects have also been possible (Jovanovic et al, 1994 Seeram and Nair, 2002). Flavonoids were originally found not to behave as efficiently as the classic phenolic antioxidants like a-tocopherol and synthetic phenolic antioxidants in donating... 

An enantioselective hydrogenation of this type is also of interest in the production of a-tocopherol (vitamin E). Totally synthetic a-tocopherol can be made in racemic form from 2,3,5-trimethylhydroquinone and racemic isophytol. The product made in this way is a mixture of all eight possible stereoisomers. 

By a combination of synthetic approaches, isotopic labeling, using tocopherols with 13C-labeling at C-5a and C-7a, EPR spectroscopy, and high-level DFT computations, it was shown that there is no radical formation at either C-5a or C-7a and that chromanol methide radical 10 does not occur in tocopherol.11 EPR failed to detect... 

Rosenau, T. Habicher, W. D. Novel tocopherol compounds I. Bromination of a-tocoph-erol—reaction mechanism and synthetic applications. Tetrahedron 1995,51,7919-7926. 

It should be noted that pharmacological vitamin E is not a free natural RRR-a-tocopherol or synthetic All rac a-tocopherol but its acetate ester. a-Tocopheryl acetate has the phenolic hydroxyl group blocked and therefore, is not a genuine antioxidant, but this compound is very rapidly hydrolyzed in vivo into a-tocopherol. It is interesting that the biological activity of a-tocopheryl acetate is the same as that of a-tocopherol in humans but significantly lower in rats [30]. ( A man is not a rat Professor KU Ingold.)... 

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). 

Tocopherols are pale yellow viscous oily substances that are insoluble in water but are soluble in fats and oils. a-Tocopherol and its acetate are made synthetically. The synthetic products are racemates and are... 

Tocopherols are not as effective as antioxidants as the synthetic antioxidants, e.g. BHA or BHT. The antioxidant effect of tocopherols is increased by mixing them with ascorbyl palmitate, ascorbic acid, lecithin or citric acid. Typical confectionery applications are the use of tocopherols with ascorbyl palmitate or lecithin or citric acid in the fat phase of toffees or caramels. Chewing gum base can be treated with a- and y-tocopherol to extend the shelf life. 

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