ω-Di-(trideuteromethyl)-tocotrienols as probes for membrane orientation and dynamics of tocotrienols

The study of the dynamic and structural role of lipids in membranes is commonly accomplished using 2H NMR and neutron diffraction. This necessarily requires the availability of specifically deuterated lipids. Our interest in the behaviour of tocopherols and tocotrienols in phospholipid membranes has shown that the tocotrienols, unsaturated forms of vitamin E, have very different effects on membrane properties as judged by differential scanning calorimetry (DSC). We report here the preparation of deuterated forms of α-, β-, and γ-tocotrienols where the terminal methyl groups on the isoprenoid side chains have been replaced with trideuteromethyl groups, thus incorporating six deuterium atoms per molecule. Starting from the naturally occurring tocotrienols, the terminal alkene can be selectively hydrobrominated with NBS, transformed to a diol and oxidatively cleaved to give a chain truncated aldehyde. The full chain length is then restored by reaction with the ylide formed by deprotonation of triphenyl-(1,2,2,2-tetradeutero-1-trideuteromethyl-ethyl)-phosphonium bromide. Copyright © 2008 John Wiley & Sons, Ltd.