A-Tocopherol side chain

Another example is the synthesis of the enantiopuxe a-tocopherol side chain [43]. Thus,the C15 allylamine, ( )(71 )-l-dimethylamino-3,7,ll-trimethyl-2-do-decene 60, was isomerized to the corresponding Cl 5 (l ,l )-enamine 61 with very high selectivities of 98% ee and 96% de (Scheme 11). 

Scheme 5. (R,R,R)-a-Tocopherol side-chain building blocks...

Investigations in our laboratories have shown that the configurations of the asymmetric centers C-4 and C-8 of the a-tocopherol side chain have, within the limits of error, no effect on vitamin E activity (antistcrility test). a-Tocopherols with different configurations at C-2, however, show within limits of error the difference of biological activity specified in the National Formulary (1960). 

A stereoselective approach to (5, )-6-methyUiept-2-en-4-ol 87, a key building block in the synthesis of a-tocopherol side chain (Scheme 30.18), was proposed by Noyori et al. via asymmetric hydrogenation of ( )-6-methyIhept-2-... 

A synthesis of (S)-cx-tocotrienol, in which the phytyl group of tocopherol is replaced by a famesyl side chain, (six steps, 19% ee = 98%) is based on the enzymatic desymmetrisation of the achiral 2,2-di(hydroxymethyl)chroman 16 <02TL7971>. 

As shown in Eigure 4.1, there are eight vitamers of vitamin E the tocopherols and the tocotrienols differ in that the tocopherols have a saturated side chain,... 

Tocopherols Tocopherols are heterocyclic compounds with a phenolic group and a substituted side chain of branched hydrocarbon. Their high solubility in oil is caused by a long alkyl side chain. The Codex Alimentarius (Codex-Stan 210-1999) indicates levels of tocopherols and tocotrienols in crude regular sunflower oil (mg/kg), compiled in Table 5. 

Tocopherols Tocopherols are widely distributed in nearly all vegetable oils but not in animal fats. Their basic structure consists of the hypothetic tocol molecule, a chromanol structure with a farnesyl side chain, substituted by one, two, or three methyl groups in the positions 5, 7, or 8. (Figure 5). A homologous... 

Plastochromanol-8 is a derivative of y-tocotrienol which has a longer side chain. This compound was detected in canola and flax oils and its antioxidative activity was established to be similar to a-tocopherol (Zambiazi 1997). 

The term vitamin E describes a family of eight antioxidants, a-, P-, y-, and 5-tocopherol and a-, P-, y-, and 5-tocotrienol, which are synthesized only by plants. Tocopherols and tocotiienols are characterized by a substituted hydroxylated ring system (chromanol ring). However, tocotrienols have an unsaturated side chain, while tocopherols have a saturated side chain with three asymmetric carbon atoms (Figure 21.2). Out of eight possible tocopherol stereoisomers, only the AAA-stereoisomer occurs naturally. ... 

Simon metabolites Initially, two major metabolites of a-tocopherol, the Simon metabolites (tocopheronic acid and tocopheronolactone) were described. Since they have a shortened side chain and an opened chroman structure, they are often quoted to demonstrate the antioxidant function of a-tocopherol in vivo. These metabolites are excreted in the urine as glucuronides or sulfates. The level of these metabolites increases markedly in the urine of healthy volunteers after a daily intake of 2 to 3 g all rac-a-tocopherol. 

Tocopherols and tocotrienols comprise the group of eight chromanol homologs that possess vitamin E activity in the diet. They are natural monophenolic compounds with varying antioxidant activities. The a-, P-, y-, and 5-tocopherols are characterized by a saturated side chain consisting of three isoprenoid units, whereas their corresponding tocotrienols have double bonds at the 3, 7, and 11 position of the isoprenoid side chain (Figure 5.3). 

An iterative Claisen rearrangement starting from allylic ester 38 was used in the synthesis of the tocopherol side chain 42 and pine sawfly pheromones (Scheme 5.2.12) [24]. Ireland-Claisen rearrangement of (Z)-allylic ester 38 and in situ reduction of the silyl ester afforded alcohol 39 as a single product Completion... 

Tocotrienols differ from tocopherols by the presence of three isolated double bonds in the branched alkyl side chain. Oxidation of tocopherol leads to ring opening and the formation of tocoquinones that show an intense red color. This species is a significant contributor to color quaUty problems in oils that have been abused. Tocopherols function as natural antioxidants (qv). An important factor in their activity is their slow reaction rate with oxygen relative to combination with other free radicals (11). 

Scheme 9. Synthesis of the side chain of a-tocopherol by Noyori et al.

Tocopherols and tocotrienols belong to the vitamin E family of compounds, which are potent antioxidants. The four isomers of tocotrienols (a-T3, P-T3, y-T3, 8-T3) are structurally related to their corresponding homologues of tocopherols (a-T, p-T, y-T, 8-T), but differ in their side-chain in that T3... 

Tocopherol can be produced as the pure 2R,4 R,8 R stereoisomer from natural vegetable oils. This is the most biologically active of the stereoisomers. The correct side-chain stereochemistry can be obtained using a process that involves two successive enantioselective hydrogenations.28 The optimum catalyst contains a 6, 6 -dimethoxybiphenyl phosphine ligand. This reaction has not yet been applied to the enantioselective synthesis of a-tocopherol because the cyclization step with the phenol is not enantiospecific. 

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