Synthesis of cytochrome P450 inhibitors of vitamin E metabolism
Ohnmacht, Stephan Alexander
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Vitamin E is a group of eight different tocopherols and tocotrienols distinguished by the degree of methylation of the aromatic ring. The North American diet contains more ytocopherol than the more biologically active a-tocopherol. y-Tocopherol has recently been shown to have several advantages over its more heavily studied a-analogue such as the trapping of electrophilic mutagens such as peroxynitrite. Cytochrome P450 preferentially metabolizes y-tocopherol over all other tocopherols begilming with an (0- hydroxylation on the phytyl side chain. Whether a single enzyme (CYP4F2) or several isozymes (such as the CYP3A family) are responsible for this action has remained controversial. We herewith repOli the synthesis of a highly potent inhibitor of the oxidative metabolism of tocopherols and tocotrienols and the subsequent biological testing in human cell lines to detennine the active enzyme of vitamin E metabolism.