SYNTHESIS AND BIOCHEMISTRY OF ASCORBIC ACID ANALOGUES

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Ascorbic acid (vitamin C), a dietary requirement for human health, is an electron donor for several enzymatic actions, functions as an antioxidant, and is implicated in host defense mechanisms, endocrine function and the visual process (lens). Recent renewed interest in the biochemistry of ascorbic acid has been prompted by the realization that relatively little is known concerning the concentrations of the vitamin required for optimum functioning of these several roles. In the case of enzymatic reactions, optimal rate of a process is defined as that concentration that allows the reaction to reach Vmax without toxicity. As part of a program to determine these concentrations, in situ kinetic measurements have been carried out for certain vitamin C-linked reactions. In addition to examination of functional roles of vitamin C, recent characterization of efficient transport mechanisms that translocate vitamin C across cellular membranes has emphasized the importance of the vitamin too biological processes. Kinetic parameters of these transport mechanisms are also being determined. As part of a program to study the effects of structural modification of vitamin C function and to provide biochemical tools for vitamin C research, we have prepared the known 6-halo-6-deoxy analogues. Kinetic measurements of transport inhibition of these analogues have clearly demonstrated the presence of separate pathways for the translocation of ascorbic acid and dehydroascorbic acid. We have now developed routes to 6-aryloxy-ascorbic acid analogues through displacement of triflate esters of gulonolactone intermediates. This versatile procedure has permitted introduction of functional groups on the 6-aryl ring. Using such functionalized analogues as starting points, various tracers and affinity labels will be introduced.