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 reactions, 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 to biological processes. Kinetic measurements of transport inhibition of 6-deoxy-6-haloascorbic acid analogues have clearly demonstrated the presence of separate pathways for the translocation of ascorbic acid and dehydroascorbic acid. We have synthesized radiolabelled 6-deoxy-6-iodoascorbic acid as a tool for studying additional details of the ascorbic acid transport system. To investigate the importance of the 2-hydroxyl group on ascorbic acid activity, we prepared 2-deoxy-ascorbic acid. This analogue was used to prepare 2-deoxy-2-halo ascorbic acids, including 2-deoxy-2-fluoro-ascorbic acid, an isosteric and isopolar, non-oxidizable, analogue. The cyclic hemiketal form of 2,2-difluoro-2-deoxyascorbic acid also was prepared, a structure which corresponds to the cyclic hemiketal form of dehydroascrobic acid. The biological properties of these new compounds are under investigation.