Rac-a-Tocopherol

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

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... 

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.)... 

Vitamin E RRR- a-tocopherol all-rac- a-tocopherol HepG2 dose response No difference in EC50 or IC50 [17]... 

This first example of a Bi(OTf)3-catalyzed Friedel-Crafts alkylation originated in the following procedures, including benzylations of 2,4-pentanediones or hydroarylation and hydroalkylation reactions. A related procedure was simultaneously developed by Bonrath et al. [39]. The authors utilized Bi(OTf)3 in the synthesis of (all-rac)-a-tocopherol (Vitamin E) [39], Besides rare earth metal triflates, such as Ga(OTf)3, Hf(OTf)3, Sc(OTf)3 and Gd(OTf)3, Bi(OTf)3 was shown to be the most efficient catalyst for the Friedel-Crafts-type reaction between trimethylhydroquinone acetate 10b and isophytols 11a, b. With only 0.02 mol% Bi(OTf)3 (substrate to catalyst ratio 5,000 1) the desired a-tocopherols 12a and 12b were isolated in excellent yields (Scheme 10). 

Determination of vitamin E different matrices Determination of all-rac-a-tocopherol in virgin olive oil... 

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. 

AOAC official method 992.03. Vitamin E activity (all-rac-a-tocopherol) in milk-based infant formula. Liquid chromatographic method. In MP Bueno, ed. Official Methods of Analysis of AOAC International. 16th ed. Arlington, VA AOAC International, 1995, p. 50-4-50-5. 

A related transformation is the rearrangement-aromatization of ketoisophorone to trimethylhydroquinone diacetate, an intermediate in the industrial synthesis of (all-rac)-a-tocopherol. Of heterogeneous catalysts, Nafion-silica exhibited the best catalyst performance858 [Eq. (5.313)], but activities decreased with repeated use because of the leaching of Nafion resin. 

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... 

All-rac-a-Tocopherol occurs as a yellow to amber, clear, viscous oil. It is a form of vitamin E. It oxidizes and darkens in air and on exposure to light. It is insoluble in water freely soluble in alcohol and miscible with acetone, with chloroform, with ether, with fats, and with vegetable oils. 

Labeling All label claims that are in terms of International Units (IU) should be based on the following 1 mg of all-rac-a-Tocopherol = 1.1 IU. 

Procedure Chromatograph 2 to 5 xL of the Assay Preparation, and record the chromatogram as described under Calibration. Measure the areas under the major peaks occurring at relative retention times of approximately 0.51 (a-tocopherol) and 1.00 (hexadecyl hexadecanoate), and record the values as ajj and ah respectively. Calculate the weight, in milligrams, of all-rac-a-Tocopherol in the sample by the formula... 

Assay, Acidity, and Optical (Specific) Rotation Determine as directed in the monograph for all-rac-a-Tocopherol. Lead Determine as directed in the Flame Atomic Absorption Spectrophotometric Method under Lead Limit Test, Appendix IIIB, using a 10-g sample. 

Gum Arabic Ammonia Solution All-rac-a-Tocopherol RRR-a -T ocopherol RRR-Tocopherols Concentrate, Mixed RRR-a-Tocopheryl Acetate All-rac-a-Tocopheryl Acetate RRR-a-Tocopheryl Acetate Concentrate RRR-a-Tocopheryl Acid Succinate... 

The U.S./Canadian Dietary Reference intakes report (Institute of Medicine, 2000) departed from tradition by considering only the contribution of the 2R isomers to vitamin E intake, and proposed an equivalence of 0.45 iu per mg for synthetic all-rac-a-tocopherol, although in consideration of upper tolerable levels of intake (Section 4.6.1), they considered the contribution of aU isomers equally However, although the 2S isomers have a shorter half-life than -tocopherol in the circulation, and hence a lower apparent biological availability, they are active in animal biological assays (Hoppe and Krennrich, 2000). 

Commercially, tocopherol is available as a pure all-rac-a-tocopherol, mixed tocopherols having various contents of a-, p-, y-, or 8-tocopherols (diluted in vegetable oil) and synergistic mixtures containing tocopherols, ascorbyl palmitate or other antioxidants, and synergists such as lecithin, citric acid, and carriers. Extraction of tocopherols from natural sources and chemical synthesis of tocopherols are well described by Schuler (100). 

Based on these biological data, two commercial forms of a-tocopherol (or their more stable acetate derivatives) are currently being produced by independent approaches [7, 8], Totally synthetic vitamin E, which is an equimolar mixture of all eight stereoisomers of a-tocopherol, is produced at a rate of over 25000 tons per year for the application in feed, food, and the pharma industry. The large-scale industrial synthesis of (all-rac)-a-tocopherol uses 2,3,5-trimethylhydroquinone (11) as the aromatic building block and the C2o compound isophytol (12). The acid-catalyzed condensation reaction in the last step delivers (all-rac)-3 (Fig. 2) [21-25],... 

---