Vitamin E Chemistry. Studies into Initial Oxidation Intermediates of α-Tocopherol:  Disproving the Involvement of 5a-C-Centered “Chromanol Methide” Radicals

Abstract

Contrary to concepts handed down in the literature from the early days of vitamin E research, one-electron oxidation of vitamin E does not involve 5a-C-centered radicals. A combined approach of analytical techniques, in particular electron paramagnetic resonance spectroscopy (EPR), organic synthesis of special derivatives, isotopic labeling, kinetic studies, and computational chemistry was used to re-evaluate the one-electron and two-electron oxidation chemistry of alpha-tocopherol (alpha-toc). EPR in combination with 5a-13C-labeled compounds provided no indication of the involvement of 5a-C-centered radicals. Oxidation of special tocopherol derivatives were used to disprove the occurrence of 5a-C-centered one-electron intermediates. Additionally it was shown that those vitamin E reactions that were commonly evoked to plead for the involvement of C-centered tocopheryl radicals actually proceeded via heterolytic, i.e., non-radical, intermediates. The results will help to clear widely spread misunderstandings about the chemistry of vitamin E and will have mechanistic implications for the synthesis of tocopherol-based supramolecular structures and 5a-substituted alpha-tocopherol derivatives.

Tocopherols by Hydride Reduction of Dialkylamino Derivatives

“…The higher resistance of 6a to hydride reduction compared with 7a was also observed in the preparation of [C 7 -13 C]-α-tocopherol from 7-(morpholino-[ 13 C]-methyl)-β-tocopherol using NaCNBH 3 (iBuOH reflux, 5 equiv., [BH 3 -] = 0.8 ), in which the desired labelled α-tocopherol was recovered in 34 % yield after 6 h together with the unreacted aminomethylated precursor. [15] These findings suggest that the hydride reduction proceeds through an o-quinomethide intermediate, with the 5-position being highly preferred over the 7-position, as reported previously. [14] Interestingly, Bu 4 NBH 4 provided the best hydride loading/conversion ratio, but we did not find reaction conditions to completely avoid the formation of n-butyl ether 11.…”

Formation of pristane from α-tocopherol under simulated anoxic sedimentary conditions: A combination of biotic and abiotic degradative processes

“…Indeed, it is very difficult to avoid the presence of traces of oxygen in the slurries and moreover some components of the sediments or microbial mats (such as hydroperoxides; Marchand and Rontani, 2001) may play the role of radical initiators (Rontani et al, 2007). Consequently an autoxidation of a-tocopherol (which is very reactive towards this process; Liebler et al, 1990;Rosenau et al, 2007;Rontani et al, 2007Rontani et al, , 2008 during the incubation cannot be totally excluded. The involvement of autoxidation is well supported by the detection of small amounts (ranging from 0.3% to 1.1% of the initial substrate) of 4,8,12,16-tetramethylheptadecan-4-olide (a characteristic autoxidation product of a-tocopherol; Rontani et al, 2007) in most of the extracts analyzed.…”

“…doi:10.1016/j.gca.2009.09.028 (Goossens et al, 1984). However, the very high efficiency of autoxidation (Liebler et al, 1990;Rosenau et al, 2007;Rontani et al, 2007), photooxidation (Grams et al, 1972;Krol et al, 2001;Nassiry et al, 2009) and aerobic biodegradation processes (Rontani et al, 2008) towards a-tocopherol suggests that only a small part of intact tocopherols should enter the sedimentary record. These compounds could thus be a likely source of pristane only in environments with high primary production or where sediments are buried under strongly reducing conditions.…”

Antioxidative and Anticorrosive Properties of Bioglycerol

“…Of course it has to be kept in mind, that oxidation initiated by different reactions (i.e. photolysis) or in different solvents may result in creation of another kind of radicals (Rosenau et al, 2007). When discussing the EPR parameters of the trapped radicals it is very important to take special consideration on the solvent used for measurements.…”