Synthesis And Biochemistry Of Ascorbic Acid Analogues

抗坏血酸（维生素 C）是人类健康的饮食必需品，是多种酶促作用的电子供体，具有抗氧化剂的作用，并与宿主防御有关 机制、内分泌功能和视觉过程（晶状体）。最近人们对抗坏血酸的生物化学产生了新的兴趣，因为人们认识到人们对抗坏血酸的了解相对较少。 关于实现这几种作用的最佳功能所需的维生素浓度。在酶促反应的情况下，过程的最佳速率定义为使反应达到 Vmax 而无毒性的浓度。作为确定这些浓度计划的一部分，我们对某些维生素 C 相关反应进行了原位动力学测量。除了检查维生素 C 的功能作用外，最近 维生素 C 跨细胞膜转运的有效转运机制的表征强调了维生素对生物过程的重要性。在之前的工作中，我们合成了放射性标记的 6-脱氧-6-碘抗坏血酸作为研究抗坏血酸转运系统其他细节的工具。运输研究表明，这将是尝试分离抗坏血酸运输蛋白​​的有用工具。为了研究2-羟基对抗坏血酸活性的重要性，我们之前还制备了2-脱氧-抗坏血酸和2-脱氧-2-卤代抗坏血酸，包括2-脱氧-2-氟抗坏血酸，一种等排和等极性、不可氧化的类似物。此外，还制备了2,2-二氟-2-脱氧抗坏血酸的环状半缩酮形式，其结构对应于脱氢抗坏血酸的环状半缩酮形式。作为一种额外的工具，我们现在制备了一种抗坏血酸类似物，其中含有可光活化的三氟甲基二氮丙啶部分作为潜在的光亲和标签。正在研究这些类似物的转运特性以及它们对谷氧还蛋白（将脱氧抗坏血酸还原为抗坏血酸的酶）的影响。

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 to biological processes. In previous work, we synthesized radiolabelled 6-deoxy-6-iodoascorbic acid as a tool for studying additional details of the ascorbic acid transport system. Transport studies indicate this will be a useful tool in attempts to isolate the ascorbic acid transport protein. To investigate the importance of the 2-hydroxyl group on ascorbic acid activity, we also previously prepared 2-deoxy-ascorbic acid, and 2-deoxy-2-halo ascorbic acids, including 2-deoxy-2-fluoroascorbic acid, an isosteric and isopolar, non-oxidizable, analogue. In addition, the cyclic hemiketal form of 2,2-difluoro-2-deoxyascorbic acid also was prepared, a structure that corresponds to the cyclic hemiketal form of dehydroascrobic acid. As an additional tool, we now have prepared an ascorbic acid analogue that contains a photoactivatable trifluoromethyl diazirine moiety as a potential photoaffinity label. Transport properties of these analogues, as well as their effects on glutarodoxin, the enzyme that reduces deoxyascorbic acid to ascorbic acid, are being investigated.