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。 用6-溴-6-脱氧抗坏血酸进行的实验表明，氧化形式（6-溴-脱氧抗坏血酸）不被葡萄糖转运体转运，葡萄糖转运体本身转运脱氧抗坏血酸。另一方面，我们以前已经表明，6-溴-6-抗坏血酸是由抗坏血酸转运蛋白。一个工作假设是，它是由transmprot蛋白识别的脱氢抗坏血酸的环状缩酮形式。氧化的6-溴-6-脱氧抗坏血酸不可能形成这样的环状缩酮。 在一个新的方法来研究抗坏血酸葡萄糖转运，我们正在制备新的黄酮类似物，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。已经制备了一系列氟化查耳酮，并将在产生类黄酮结构的条件下环化。

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. Experiments with 6-bromo-6-deoxyascorbic acid have revealed that the oxidized form (6-bromo-deoxyascorbic acid) is not transported by the glucose trasporter that translocates deoxyascorbic acid itself. On the other hand, we had shown previously that 6-bromo-6-ascorbic acid is transported by the ascorbic acid transport protein. A working hypothesis is that it is the cyclic ketal form of dehydroascorbic acid that is recognized by the trasmprot protein. It is impossible for oxidized 6-bromo-6-deoxyascorbic acid to form such a cyclic ketal. In a new approach to the study of ascorbic acid glucose transport, we are preparing new 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. A series of fluorinated chalcones have been prepared and will be cyclized under conditions that produce the flavonoid structures.