Tocopherol acetate

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). 

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 a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

Stopped-flow H C-HSQC NMR spectrum of a-tocopherol acetate. 

Figure 4 Chemical structure of a-tocopherol and a-tocopherol acetate...

For non-standardised products tocopherols, tocopherol acetate, ascorbic acid and its sodium and calcium salts, ascorbyl palmitate, ascorbyl stearate, eiythorbic acid and stannous chloride (max. 0.0015% calculated as tin) may be used according to good manufacturing practice. 

Tocopherol acetate 0.3 g Diphenyl amine Each ml of 0.1 N ammonium ceric sulphate = 0.002364 g of C31H5203... 

Consequently, soil samples from feedlots have a dual origin of toco-pherols. This is illustrated with the GC-MS data of a study done in the San Joaquin Valley of California (Fig. 5b, ). The y-tocopherol is derived exclusively from the vegetation fodder, while a-tocopherol is derived from both vegetation and the hydrolysis of the tocopheryl acetate feed supplement. Excess a-tocopherol acetate, not hydrolyzed in the animal gut, is also present. Because a-tocopherol acetate is relatively stable, its presence in soil dust samples indicates the level of its usage as a feed supplement. A significant metabolite of a-tocopherol elutes after the acetate and the... 

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles has been developed. In recent years, solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system... 

Figure F3.3.3 Comparison of subjective sensory assessment (A percent discoloration) and objective colorimetric evaluation (B hue angle). Beef was obtained from cattle supplemented with 0 (E-0), 500 (E-500) or 2000 (E-2000) IU a-tocopherol acetate per head per day. The a-tocopherol demonstrated a color preservation effect. Hue angle was calculated as [tan-1(b7a )] (36072rc). Standard error bars are indicated. Adapted from Chan et al. (1995), with permission from the Institute of Food Technologists.

Andrikopoulos et al. (124) separated triglycerides, together with nine synthetic phenolic antioxidants most commonly used to prevent oxidation of edible oils and fats, as well as the natural antioxidants tocopherol and alpha-tocopherol acetate by HPLC using a reversed-phase Cl8 column and gradient elution with water/acetonitrile/methanol/isopropanol. Except for dilution of the oil with isopropanol/hexane, no further sample preparation was required. Ultraviolet detection was applied. The synthetic antioxidants PG, OG, DG, BHA, TBHQ, BHT, Ionox 100, THBP, and NDGA, as well as alpha- and delta-tocopherol and alpha-tocopherol acetate were separated. 

Heteropolyacids catalyze the condensation reaction in the synthesis of vitamin E (a-tocopherol acetate) as shown in Eq. (42) (362). 

Clinical investigations of the use of vitamin E in treating vascular disorders associated with hypoxia have been more successful [194]. In intermittent claudication, Boyd, Ratcliffe, Jepson and James [195] reported a 78% improvement over a 6 month trial period, while Haeger [ 196, 197] observed significant increases in walking distance in patients with intermittent claudication receiving 300 mg a-tocopherol acetate per day for 2-5 years. This condition currently represents the most potentially useful clinical area for administration of the vitamin in pharmacological doses. 

Figure 1.11 UV chromatograms (295 nm) of the separation of tocopherol isomers (1, 8-tocopherol 2, 7-tocopherol 3, (3-tocopherol 4, a-tocopherol 5, a-tocopherol acetate (a) analytical separation (b) with a 200-fold amount of sample...

Vitamin E is required for normal growth and reproduction. The most important natural source is a-tocopherol found in plant oils and seeds. The ester form (e.g. vitamin E acetate) can be synthesized and is used for feed supplementation. One international unit is defined as being equivalent to the activity of 1 mg DL-a-tocopherol acetate. The nutritional role of vitamin E is closely interrelated with that of selenium and is involved mainly in the protection of lipid membranes such as cell walls from oxidative damage. Although these signs are similar to those of selenium deficiency, it is not possible to substitute selenium completely for vitamin E. Both nutrients are required in the diet. 

Masuda et al. have reported the supercritical fluid chromatography of retinol palmitate and tocopherol acetate using an octadecylsilyl silica gel column with ethanol-modified carbon dioide as the mobile phase [43]. Both retinol and tocophenol eluted within 5 min. The method was applied to the determination of these compounds in an ointment formulation. The method was found to be linear for both retinol and tocophenol from 0.5 to... 

Since vitamin E is very sensitive to oxidation, stable esters have mainly been used for topical formulations and are considered to be safe.64 As had previously been shown for skin of hairless mice,65 but not for human skin,66 the bioconversion of vitamin E acetate by esterases to vitamin E with its known antioxidant effects has recently also been demonstrated in human skin.48 When supplemented orally a-tocopherol acetate or a-tocopherol succinate get readily hydrolyzed to a-tocopherol in the gut47 with the natural single stereoisomeric form (RRR-a-tocopherol) appearing to have about twice the systemic availability of the synthetic form (all-rac-a-tocopherol)67... 

In a hemiface trial in humans 5% vitamin E reduced rhytides, skin roughness, length of facial lines, and depth of wrinkles more than vehicle.68 Topical tocopherol acetate was also shown to significantly increase stratum corneum hydration in human volunteers with additionally enhancing the water-binding capacity as compared to vehicle. The optimum concentration for these effects was 5% tocopherol acetate.69... 

Alberts, D.S. et al., Disposition and metabolism of topically administered alpha-tocopherol acetate a common ingredient of commercially available sunscreens and cosmetics, Nutr. Cancer, 26, 193, 1996. 

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