5-Trideuteromethyl-alpha-tocotrienol and 5-~(14)CH_3-alpha-tocotrienol as biological tracers of tocotrienols

摘要

The tocotrienols have attracted increased attention recently as evidence has accrued that their biological activities are significantly different from tocopherols. The biokinetics and metabolic fate of tocopherols have long been studied using deuteromethylated forms of alpha-tocopherol prepared by a stannous chloride catalysed paraformaldehyde methylation of gamma- and delta-tocopherols. We show here that his methodology is not an efficient route to deuterated a-tocotrienol because of low yields and extensive exchange of allylic hydrogens under the prolonged acidic conditions of the deuteromethylation. Instead, we have prepared deuteromethylated and ~(14)C-radiolabelled a-tocotrienol by aminomethylation at C-5 of gamma-tocotrienol (available from palm oil), followed by reduction with NaCNBD_3 in refluxing iso-butanol. The deuteromethylation procedure is amenable to multi-gram scale reactions.