A- tocopherol

The antagonisms that exist between unsaturated fatty acids, and carotene and vitamin E are compHcated and largely undefined. Linoleic acid acts as an antivitamin to i7/-a-tocopherol [59-02-9, 1406-18-9, 10191-41-0] (vitamin E) by reducing availabiHty through direct intestinal destmction. Various Hpoxidases destroy carotenes and vitamin A (73). Dicoumarol [66-76-2] (3,3 -methylenebis(4-hydroxycoumarin)) is a tme antimetaboHte of vitamin K [12001 -79-5] but seems to occur only in clover and related materials that are used primarily as animal feeds (74). 

X5lenol is an important starting material for insecticides, xylenol—formaldehyde resins, disinfectants, wood preservatives, and for synthesis of a-tocopherol (vitamin E) (258) and i7/-a-tocopherol acetate (USP 34-50/kg, October 1994). The Bayer insecticide Methiocarb is manufactured by reaction of 3,5-x5lenol with methylsulfenyl chloride to yield 4-methylmercapto-3,5-xylenol, followed by reaction with methyl isocyanate (257). Disinfectants and preservatives are produced by chlorination to 4-chloro- and 2,4-dich1oro-3,5-dimethylpheno1 (251). 

Inhibition of nitrosation is generally accompHshed by substances that compete effectively for the active nitrosating iatermediate. /V-Nitrosamine formation in vitro can be inhibited by ascorbic acid [50-81-7] (vitamin C) and a-tocopherol [59-02-9] (vitamin E) (61,62), as well as by several other classes of compounds including pyrroles, phenols, and a2iridines (63—65). Inhibition of iatragastric nitrosation ia humans by ascorbic acid and by foods such as fmit and vegetable juices or food extracts has been reported ia several instances (26,66,67). 

RRR)-a-tocopherol, (RRR)-a-tocopheryl acetate, all-rai -a-tocopherol, all-rai a-tocopheryl acetate, all-rai a-tocopheryl succiaate... 

Vitamin E was first described ia 1922 and the name was originally applied to a material found ia vegetable oils. This material was found to be essential for fertility ia tats. It was not until the early 1980s that symptoms of vitamin E deficiency ia humans were recognized. Early work on the natural distribution, isolation, and identification can be attributed to Evans, Butt, and Emerson (University of California) and MattiU and Olcott (University of Iowa). Subsequentiy a group of substances (Eig. 1), which fall iato either the family of tocopherols or tocotrienols, were found to act like vitamin E (1 4). The stmcture of a-tocopherol was determined by degradation studies ia 1938 (5). 

Fig. 1. The four naturally occutting tocopherols (a-tocopherol, E.E.E. [59-02-9] jall-rac [2074-53-5] (1) p-tocopherol [148-03-8] (2) y-tocopherol [54-28-4] (3) 8-tocopherol [119-13-1] (4)), a-tocotrienol [1721 -51 -3] (5), and p-tocotrienol [14101-61-2] (6) where asterisks denote asymmetric centers and the...

Unesterified tocopherols are found in a variety of foods however, concentration and isomer distribution of tocopherols vary gready with source. Typically, meat, fish, and dairy contain <40 mg/100 g of total tocopherols. Almost all (>75%) of this is a-tocopherol for most sources in this group. The variation in the content of meat and dairy products can be related to the content of the food ingested by the animal. A strong seasonal variation can also be observed. Vegetable oils contain significant levels of y-, P-, and 5-tocopherol, along with a-tocopherol (Table 3). 

Oil source Total tocopherols a-Tocopherol y-Tocopherol (3-Tocopherol 5-Tocopherol... 

Fig. 3. Synthesis via trimethyUiydroquinone [700-13-0] (TMHQ) (13) and isophytol [505-32-8] (14) of a-tocopherol (15a) and a-tocopherol acetate (15b).

The yield of the more active RRR-a-tocopherol can be improved by selective methylation of the other tocopherol isomers or by hydrogenation of a-tocotrienol (25,26). Methylation can be accompHshed by several processes, such as simultaneous halo alkylation and reduction with an aldehyde and a hydrogen haUde in the presence of staimous chloride (27), amino alkylation with ammonia or amines and an aldehyde such as paraformaldehyde followed by catalytic reduction (28), or via formylation with formaldehyde followed by catalytic reduction (29). 

The all-rac forms of P-, y-, and 5-tocopherols can be synthesized using the same condensation reaction as used for i7//-n7iC-a-tocopherol. To synthesize i7//-n7iC-P-tocopherol, 2,5-dimethylhydroquinone instead of trimethyUiydroquinone is condensed with isophytol. For all-rac- - and 5-tocopherol, 2,3-dimethylhydroqiiinone and methyUiydroquinone are used, respectively. 

Although apparendy not commercially important, fermentation (qv) processes have been reported for the production of tocopherols. yispergillus niger (30), iMctohacter (31), Eugknagracilis Z. (32,33), and Mjcohacterium (34) have been shown to produce (RRR)-a-tocopherol. In the case of Eug/ena, titers of 140—180 mg/L have been reported. 

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

Label claims for tocopherol levels in preparations can be based on milligrams or International Units. Only the RRR or all-rac-International Units ate also used in some reference books and compendia, eg. Food Chemicals Codex (40,53), which is of particular importance for specifications for food fortification. 

AH formulations of vitamin E must show low acidity, and contain not more than 0.004% heavy metals (reported as Pb) and not more than 10 ppm Pb. Eormulations that contain RRR-a-tocopherol must have a specific rotation of +24 ° for the oxidation product with alkaline potassium ferricyanide. 

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