Synthesis And Biochemistry Of Ascorbic Acid Analogues

抗坏血酸（维生素C）是人类健康所需的膳食，是几种酶作用的电子供体，具有抗氧化剂的功能，并与宿主防御机制、内分泌功能和视觉过程（晶体）有关。最近，人们对抗坏血酸的生物化学重新产生了兴趣，这是因为人们认识到，对这几种作用的最佳功能所需的维生素浓度所知相对较少。在酶促反应的情况下，一个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。作为确定这些浓度计划的一部分，已经对某些维生素c相关反应进行了原位动力学测量。除了研究维生素C的功能作用外，最近对维生素C跨细胞膜转运的有效运输机制的描述也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，作为研究抗坏血酸运输系统的额外细节的工具。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，我们之前还制备了2-脱氧抗坏血酸和2-脱氧-2-halo抗坏血酸，包括2-脱氧-2-氟抗坏血酸，这是一种等同异极性、不可氧化的类似物。此外，还制备了2,2-二氟-2-脱氧抗坏血酸的环半柱状结构，该结构与脱氢抗坏血酸的环半柱状结构相对应。

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.