Synthesis And Biochemistry Of Ascorbic Acid Analogues

抗坏血酸（维生素C）是人类健康的膳食必需品，是几种酶促作用的电子供体，起抗氧化剂的作用，并且涉及宿主防御机制、内分泌功能和视觉过程（透镜）。最近对抗坏血酸的生物化学重新产生了兴趣，这是由于人们认识到，对于这几种作用的最佳功能所需的维生素浓度，人们知之甚少。在酶促反应的情况下，过程的最佳速率被定义为允许反应达到Vmax而没有毒性的浓度。作为确定这些浓度的计划的一部分，已对某些维生素C相关反应进行了原位动力学测量。除了维生素C的功能作用的检查，最近的表征，跨细胞膜转运维生素C的有效运输机制，强调了维生素的重要性，生物过程。在以前的工作中，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的其他细节的工具。转运研究表明，这将是一个有用的工具，试图分离抗坏血酸转运蛋白。为了研究2-羟基对抗坏血酸活性的重要性，我们先前还制备了2-脱氧-抗坏血酸和2-脱氧-2-卤代抗坏血酸，包括2-脱氧-2-氟代抗坏血酸，其为等排和等极性的不可氧化的类似物。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。作为一个额外的工具，我们准备了一个抗坏血酸类似物，含有一个光活化的三氟甲基双吖丙啶部分作为一个潜在的光亲和标记。这些类似物的传输特性，以及它们对戊二氧还蛋白的影响，酶，还原脱氧抗坏血酸抗坏血酸，进行了研究。初步结果表明，类似物有效地阻止抗坏血酸运输，但本身不运输。迄今为止，光化学实验还没有定论。 在研究抗坏血酸葡萄糖转运的新途径中，我们正在制备新的类黄酮类似物，以研究这些抗坏血酸和葡萄糖转运抑制剂的结构参数。将包含转运蛋白的潜在亲和标记。并探讨了氟取代对黄酮类化合物生物活性的影响。

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 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,wereinvestigated. Initial results show that the analogue effectively blocks ascorbate transport, but itself is not transported. Photochemical experiments to date have been inconclusive. In a new approach to the study of ascorbic acid glucose transport, we are preparing neow flavonoid analogues to study sturtural parameters of these inhibitors of ascorbate and glucose transport. Inculded will be potential affinity labels for the transport protein(s). Effects of fluorine substitution biolgical begavior of the flavonoids also will be examined.