8- Methyl-tocol

S. L. Abidi and T. L. Mounts, Separations of tocopherols and methylated tocols on cyclodextrin-bonded silica, J. Chromatogr., A 664 130 (1994). 

Structures of naturally occurring plant compounds having vitamin E activity. The nucleus in each is 6-hydroxychroman. Attachment of a saturated 16-carbon chain produces the tocopherols the tocotrienols have a 16-carbon unsaturated chain. Both groups are optically active. The tocotrienols have one chiral center at carbon 2, while the tocopherols have three, at carbons 2,4, and 8. Tocol is a tocopherol in which R i, R2, and R3 are all hydrogen atoms. The tocopherols can be viewed as methylated tocols. 

The well-known series of natural tocopherols consists of methylated tocols derived from phytol. Recently Green ct al. (1959a, 1960) showed the existence of a second, closely related series of natural tocopherols containing an unsaturated (trimethyltrideca-3,7,ll-trienyl) side chain, as represented by e- and fi-tocopherol (Table II). Further chromanols, chromenols, and benzoquinones which may play a role together with or similar to that of vitamin E in the living cell are also listed in Table II. 

Tocopherol. Any of a series of structurally similar compounds, methyl-substituted tocols. 

Figure D1.5.1 Structure of tocol 2-methyl-2-(4, 8, 12 -trimethyltridecyl)chroman-6-ol.

In reversed-phase HPLC on a Cl8 column, only six peaks are usually found, and their order of elution is 5-tocotrienol, (3- and y-to-cotrienols, a-tocotrienol, 5-tocopherol, (3- and y-tocopherol, and a-tocopherol. Figure D 1.5.4 is an example of a reversed-phase chromatograph of tocopherols and tocotrienols in rice bran oil. The tocols with unsaturated side chain have shorter retention time than those with saturated side chain. The methyl substituents on the chromanol ring also affect the retention times of tocopherols and tocotrienols. However, the effect is reversed, compared with the normal-phase HPLC method. 

The levels of cardiovascular factors could also be influenced by the ability of vitamin E to affect activation of arachidonic acid from membrane phospholipids by phospholipase A2. Vitamin E, either given in the diet or by incubation with platelets themselves, was found to inhibit phospholipase A2 in a dose-dependent manner. a-Tocopheryl acetate had little or no effect on the activity of this enzyme, but tocol, without methyl groups in the chroman ring, was more potent than either (+)- or ( )-a-tocopherol, suggesting that the methyl groups were not important for the inhibition but the hydroxy group in the ring was critical for activity [131]. 

Fig. 6.1. HPLC separation of a-tocopherol (peak 1), y-tocopherol (peak 2) and tocol (peak 3). (a) Using hexane and methyl-t-butyl ether (88 12), flow rate 2.0 ml/min, ambient temp., fluorescence detector, Lichrosorb Si60 column, (b) Using hexane and methyl-t-butyl ether (92 8), flowrate 2.0 ml/min, ambient temp., fluorescence detector, Lichrosorb Si60 column, (c) Using hexane and methyl-/-butyl ether (95 5), flowrate 2.0 ml/ min, ambient temp., fluorescence detector, Lichrosorb Si60 column.

In recent years several normal-phase HPLC methods have been reported for the quantitative analysis of tocopherols and tocotrienols (Table 11.5). The best of these methods have been able to achieve baseline separation of all four tocopherols and all four tocotrienols, as shown in Figures 11.2 and 11.3. Kamal-Eldin et al. (2000) reported the optimal baseline separation of all eight common tocols using a Diol-bonded phase column and an isocratic mobile phase of hexane/methyl tert-butyl ether (MTBE), 96 4, v/v (Figure 11.2). Similar separations were reported by Moreau et al. (2007) using the same type of column and mobile phase. Schwartz et al. (2008) reported that, with a normal-phase silica column, plastochromanol-8 in rapeseed oil eluted between y-tocopherol and 5-tocopherol. 

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... 

Toco], 3,4-Dihydro-2-methyl-2-(4.8.I2-trimethyl-tridecyl)-2H-l-bentopyran-6-oi 2-methyl-2-(4,8, 12-tri-me(hyltridecyl)-6-chromanoi 2-methyl -2-phytyl-6-chroma-nol 6-hydroxy-2-methyl-2-phytylch roman 2-methyl 2 phytyl-6-hydroxychroman. C H O, mol wt 388.61. C 80,35%, H 11.41%, O 8.23%. Synthesis by the condensation of hydroquin one and phytol in the presence of anhydr formic acid Pendse, Karrer, Helv. Chim. Acta 48, 1837 (1957). Antioxidant activity of tocol and its methyl derivS Olcott, van der Veen, Lipids 3, 331 (1968),... 

Tocopherols, also known as tocols, are compounds derived from 2-methyl-2-(4,8,12-trimethyl tridecyl)chroman-6-ol, and tocotrienols are compounds derived from... 

Olcott, H.S. J. Van Der Veen. Comparison of antioxidant activities of tocol and its methyl derivatives. Lipids 1968,3, 331-334. 

Except 5-methyltocol (Bacharach and Green, 1961) and tocol [2-methyl-2-(4, 8, 12 -trimethyltridccyl)-6-chromanol], all the lower homologs of a-tocopherol bearing only one or two methyl groups on the aromatic nu-... 

The tocopherols, all of which possess vitamin E activity, may be regarded as tocol derivatives, methyl-substituted (I) on the benzene ring (Table I) (Karrer and Fritzsche, 1938) ... 

The following substances were available a-, /3-, 7-, 5-, fr, if -tocopherol, a mixture of the three moiiomethyltocols in a proportion of about 1 2 1, the unsubstituted tocol, and its methyl ether. 

An almost complete separation of a-tocopherol from a-tocopheryl acetate should be specially mentioned. As Fig. 5 shows, tocol and the corresponding methyl ether can also be separated on an SE 30 column. 

No distinction can be obtained between a-tocopherol and a-tocopheryl acetate on the Apiezon N column, though tocol and tocol methyl ether are clearly separated. 

Other reactions that have been applied in the Ugi postmodification strategy are the aza-Wittig reaction [80-84] and copper-catalyzed processes [85, 86], More recently, Domling and coworkers have developed a new approach for the synthesis of polycyclic compounds via Ugi MCR followed by a Pictet-Spengler reaction [87-89]. In 2011, apro-tocol for the rapid access to quinolin-2-(l//)-one scaffold was reported by a sequential 4-component Ugi-Knoevenagel condensation [90]. Hulme et al. have introduced a one-pot, two-step protocol for large-scale production of libraries of novel peptidomimetic-like fcM-pyrrolidinone tetrazoles via the Ugi-3CR-azide reaction of tethered keto ester methyl... 

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