Vitamin lipophilic analogue

This new strategy consists of the synthesis of molecules that possess hydroxyl groups in such positions that a radical species can be stabilized by mesomery. This feature is found in natural flavonol such as kaemferol that possesses undeniable antioxidant properties. The first published example is a lipophilic analogue of vitamin C, Fig (13) [40]. In this paper, we have proved that the synthesised substituted 2-hydroxyfuran-2-one is a true ascorbic acid analogue. A radical anion that gives very similar data has been generated under the same conditions as for ascorbic acid with a stability somewhat lower and a redox potential lower than those of ascorbyl radical. Its antioxidant properties are also similar to that of ascorbic acid but it inhibits LDL peroxidation induced by Cu2+ or AAPH more efficiently probably due to a higher lipophilicity. 

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

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