SYNTHESIS AND BIOCHEMISTRY OF ASCORBIC ACID ANALOGUES

抗坏血酸(维生素C)是人类健康的饮食要求，是一种 几种酶作用的电子供体，起着 抗氧化剂，与宿主防御机制、内分泌有关 功能和视觉过程(晶状体)。最近重新燃起了对 抗坏血酸的生物化学是由于认识到 人们对维他命的浓度知之甚少。 使这几个角色发挥最佳作用所必需的。在.的情况下 酶反应，一个过程的最佳速率被定义为 使反应达到Vmax而无毒性的浓度。 作为确定这些浓度的程序的一部分，原位动力学 已经对某些与维生素C相关的物质进行了测量 反应。除了研究维生素C的功能作用外， 最近对高效运输机制的表征 维生素C跨细胞膜的转移强调了 维生素在生物过程中的重要性。动力学参数 这些传输机制中的哪些也正在确定中。 作为一个项目的一部分，研究结构修改的影响 维生素C的功能和为维生素C提供生化工具 研究中，我们制备了已知的6-卤代-6-脱氧类似物。动能 对这些类似物的运输抑制的测量清楚地表明 证明了存在不同的转位途径 抗坏血酸和脱氢抗坏血酸。 我们现在已经开发了6-芳氧基-抗坏血酸类似物的路线，通过 古龙内酯中间体三氟酸酯的置换。这 多功能程序允许将官能团引入 6-芳基环。使用这种功能化的类似物作为起点， 将推出各种示踪剂和亲和标签。

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 too biological processes. Kinetic parameters of these transport mechanisms are also being determined. As part of a program to study the effects of structural modification of vitamin C function and to provide biochemical tools for vitamin C research, we have prepared the known 6-halo-6-deoxy analogues. Kinetic measurements of transport inhibition of these analogues have clearly demonstrated the presence of separate pathways for the translocation of ascorbic acid and dehydroascorbic acid. We have now developed routes to 6-aryloxy-ascorbic acid analogues through displacement of triflate esters of gulonolactone intermediates. This versatile procedure has permitted introduction of functional groups on the 6-aryl ring. Using such functionalized analogues as starting points, various tracers and affinity labels will be introduced.