A-Tocopheryl acetate

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

The biological activity of various vitamin E forms was estabUshed by the fetal resorption assay ia tats and is assumed to be appHcable to humans. The results of some human studies may iadicate that the ratio of 1.36 underestimates the biological activity of the RRR form relative to the all-rac form of a-tocopheryl acetate (10—12). 

Property i7//-n7iva-Tocopherol RRR-a-T ocopherol all-rac-d-T ocopheryl Acetate RRR-a-Tocopheryl -Acetate... 

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. 

Table 4. Bulk Prices of Pharmaceutical-Grade a-Tocopheryl Acetate, /kg ...

Stabilization of the zwitterionic intermediate in o-QM formation can also occur intramolecularly. In this case, the stabilizing moieties must be able to dissipate the positive charge at the benzylic group by a resonance effect and prevent rotation of the exocyclic methylene group by a steric blocking. One example for such a temporary stabilization is the nitration of a-tocopheryl acetate (25) by concentrated HNO3, which produced 6-0-acetyl-5-nitro-a-tocopherol (27) in quite good yields,48 the... 

Oxo-a-tocopherol (55) proved to be a very interesting compound with regard to forming various intermediate tautomeric and quinoid structures. It undergoes an intriguing rearrangement of its skeleton under involvement of different o-QM structures. The 4-oxo-compound was prepared from 3,4-dehydro-a-tocopheryl acetate via its bromohydrin, which was treated with ZnO to afford 4-oxo-a-tocopherol (55). 

Adelwohrer, C. Rosenau, T. Kosma, P. Novel tocopheryl compounds Part 16 nitration of a-tocopheryl acetate—a mechanistic study. Tetrahedron 2003, 59(41), 8177-8182. 

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.)... 

New isoxazoline derivatives of a-tocopherol, the main component of vitamin E, have been synthesized in a facile, two-step sequence consisting of nitration followed by 1,3-dipolar cycloaddition. 5-Nitromethyl-a-tocopheryl acetate, obtained from a-tocopheryl acetate by direct nitration in one step, act as the nitrile oxide precursor in the reaction with various alkenes. The facile conversion proceeds in the presence of equimolar amounts of PhNCO and catalytic amounts of triethylamine to give isoxazolines, 446 (489). 

All of the above examples are acetates of active alcohols. Here, we also mention the acetate of a phenol, namely the provitamin a-tocopheryl acetate, whose natural enantiomer of absolute configuration (2R,47 ,87 ) is shown as 8.73. a-Tocopheryl acetate is a substrate of cholesterol esterase (EC 3.1.1.13), and was hydrolyzed in rats faster than its (2S,47 ,87 )-epimer. In vitro experiments required a-tocopheryl acetate to be dispersed as a micellar pseudosolution, and the nature of the bile salt used to prepare micelles had a profound effect on the substrate stereoselectivity of the reaction [95] [96], Only when the micelle composition approximated that of the gastrointestinal tract did the in vitro substrate stereoselectivity resemble that seen in vivo. 

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).

Arnold RN, Scheller KK, Arp SC, Williams SN, Buege DR, Schaefer DM, Effect of long- or short-term feeding of a-tocopheryl acetate to Holstein and crossbred beef steers on performance, carcass characteristics and beef color stability,/A i-mal Science 7Q 3055—5QC7, 1992. 

The main sources of these compounds are vegetable oils, unprocessed cereal grains, and nuts. The vitamin formulations that may be added to foods are o-a-tocopherol, OL-a-tocopherol, o-a-tocopheryl acetate, oL-a-tocopheryl acetate, and o-a-tocopheryl acid succinate [403],... 

Vitamin E acetate (DL-a-tocopberyl acetate) [7695-91-2] M 472.8, m -27.5°, b 194-196°/0.01mm, 222-224°/0.3mm, d 0.958, n 1.4958. It is a viscous liquid which is purified by distn under high vacuum in an inert atm and stored in sealed ampoules in the dark. It is considerably more stable to light and air than the parent unacetylated vitamin. It is insoluble in H2O but freely soluble in organic solvents. All eight stereoisomers have been synthesised. The commercially pure d-a-tocopheryl acetate (2R,4 R,8 R) has b 18O-2OO°/O.7mm and +3.9° (c 5, EtOH). [Cohen et al. HCA 64 1158 1981]. 

Table D1.5.1 Conventional Analysis Methods of a-Tocopherol and a-Tocopheryl Acetate in the AOAC International Official Methods of Analysis...

AOAC 971.30 a-Tocopherol and a-Tocopheryl Acetate in Foods and Feeds, Colorimetric Method (First Action 1971 and Final Action 1972)... 

AOAC 989.09 a-Tocopheryl Acetate in Supplemental Vitamin E Concentrates, Gas Chromatographic Method (First Action 1989)... 

The acetate ester of a-tocopherol, rather than the free alcohol, is used as a food supplement on account of its greater stability. Both 7 7 f -a-tocopheryl acetate and totally synthetic all-rac-a-tocopheryl acetate are commercially available, the former having a biological activity of 1.36 IU/mg and the latter 1.00 IU/mg (44). The / / / -a-tocopheryl acetate is obtained by extraction from vegetable oils. Since it is not isolated without some chemical processing, it cannot legally be called natural, but it can be described as derived from natural sources. 

The nutritional evaluation of the vitamin E-rich vegetable oils and the products made from them using a nonbiological assay necessitates the determination of the individual tocopherols and to-cotrienols, for these vitamers vary widely in biological activity. High-performance LC is ideally suited for this purpose, and the overall vitamin E value of such foods can be estimated by applying appropriate factors based on relative biological activities. For the analysis of those animal products known to contain predominantly a-tocopherol, only this vitamer need be determined. In vitamin E-fortified foods it is usually sufficient to determine either the added a-tocopheryl acetate or the total a-tocopherol. 

In the analysis of foods that contain significant amounts of both naturally occurring toco-pherols and supplemental a-tocopheryl acetate, saponification, by hydrolyzing the esterified vitamin E, allows the total a-tocopherol content to be measured as a single peak by HPLC. It should be noted that if totally synthetic all-rac-a-tocopheryl acetate is the supplemental form used, its hydrolysis product, all-rac-a-tocopherol, is less biologically active than is naturally occurring RRR-a-tocopherol, making it impossible to calculate a potency value for the total vitamin E. This problem does not arise if the supplement used is / / / -a-tocopheryl acetate. 

Enzymatic hydrolysis is a nondestructive alternative to saponification for removing triglycerides in vitamin K determinations. For the simultaneous determination of vitamins A, D, E, and K in milk- and soy-based infant formulas and dairy products fortified with these vitamins (81), an amount of sample containing approximately 3.5-4.0 g of fat was digested for 1 h with lipase at 37°C and at pH 7.7. This treatment effectively hydrolyzed the glycerides, but only partially converted retinyl palmitate and a-tocopheryl acetate to their alcohol forms vitamin D and phyllo-quinone were unaffected. The hydrolysate was made alkaline in order to precipitate the fatty acids as soaps and then diluted with ethanol and extracted with pentane. A final water wash yielded an organic phase containing primarily the fat-soluble vitamins and cholesterol. 

Fig. 7 Comparative HPLC separations of a standard solution of six vitamins using (A) 250 X 4.0-mm-ID standard-bore and (B) 250 X 2.0-mm-ID narrow-bore columns. Stationary phase (both columns), 5-/tm Nu-cleosil-120-5 C8 (octyl) mobile phase, methanol/water (92 8). Flow rate (A) 0.7 ml/min, (B) 0.2 ml/min. Injection volume, 1 fi 1. Wavelength-programmed absorbance detection. Peaks (1) retinol (2) retinyl acetate (3) vitamin D3 (4) a-tocopherol (5) a-tocopheryl acetate (6) retinyl palmitate. (From Ref. 108.)...

It is fortuitous that indigenous concentrations of vitamin E in the principal food sources are on the order of mg rather than yug/100 g, for the tocopherols and tocotrienols exhibit relatively low intensities of UV absorption. Individual vitamers are characterized by a slightly different absorption maximum within the wavelength range of 292-298 nm in ethanol. Published A] m values for the tocopherols at their Amax in ethanol are a-T 70-73.7 at 292 nm, (3-T 86-87 at 297 nm, y-T 90-93 at 298 nm, and <5-T 91.2 at 298 nm (126). The different absorption characteristics among the vitamers necessitates the running of individual standards for accurate quantitation of each vitamer. The absorption intensity of a-tocopheryl acetate is lower still with an A j m value of only 40-44 at the Amax of 285.5 nm (44). Reported minimum detectable quantities of a-, / -, y-, and (5-tocopherols at 295 nm are, respectively, 50 ng, 70 ng, 90 ng, and 130 ng (127). 

Amperometric detection in the oxidative mode produced on-column detection limits of 0.07, 4.3, and 0.19 ng for retinol, vitamin D3, and a-tocopherol, respectively (143). A limitation of amperometric detection in vitamin E assays is that it cannot measure a-tocopheryl acetate, owing to the absence of the oxidizable hydroxyl group. 

Breakfast cereals, infant Cereals add water and LiChrosphere lOODiol Two-step gradient com- a-Tocopheryl acetate Fluorescence 86... 

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