SYNTHESIS AND BIOCHEMISTRY OF ASCORBIC ACID ANALOGUES

抗坏血酸（维生素C）是人体健康的膳食必需品， 几种酶促作用的电子供体， 抗氧化剂，并涉及宿主防御机制，内分泌 功能和视觉过程（透镜）。 最近， 抗坏血酸的生物化学已经被这样的认识所推动， 关于维生素的浓度， 这几个角色的最佳功能。 的情况下 在酶促反应中，过程的最佳速率定义为 该浓度允许反应达到Vmax而没有毒性。 作为确定这些浓度的计划的一部分， 已经对某些维生素C相关的 反应. 除了检查维生素C的功能作用外， C，最近对有效运输机制的表征， 维生素C跨细胞膜转运强调了 维生素对生物过程的重要性。 动力学参数 这些运输机制也正在确定中。 上述工作是在营养方案、LCBG、NIDDK中开展的， 产生了与维生素C生物化学有关的有价值的信息， 代谢，并具有实际意义， 要求. 然而，在任何生物化学研究中， 天然底物的类似物将非常有用， 表征基质-大分子相互作用， 运输过程的抑制剂，作为酶抑制剂，和作为 用于共价标记功能蛋白质的潜在试剂 参与这些过程。 不幸的是，相对较少的合成 对维生素C的结构修饰进行了研究。 先前工作的实例包括制备6-卤代-6-脱氧-和 6-脱氧-抗坏血酸类似物和抗坏血酸的3-或4-O-烷基醚 酸 作为一项研究结构性影响的计划的一部分， 改变维生素C的功能，并提供生物化学工具， 维生素C的研究，我们已经制备了已知的6-卤代-6-脱氧类似物 并已启动了这些转运抑制的动力学测量， 类似物 此外，我们已经开发出了反应， 可以作为亲和标记物的新类似物的路线， 放射性示踪剂和核磁共振探针。

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. Kinetic parameters of these transport mechanisms are also being determined. The above work, carried out in the Nutrition Program, LCBG, NIDDK, has produced valuable information related to vitamin C biochemistry and metabolism, and has practical implications regarding dietary requirements. However, as in any biochemical study, structural analogues of the natural substrate would be extremely useful to further characterize substrate-macromolecule interactions, by functioning as inhibitors of transport processes, as enzyme inhibitors, and as potential agents for covalent labeling of the functional proteins involved in these processes. Unfortunately, relatively little synthetic work has been carried out on structural modifications of vitamin C. Examples of previous work include the preparation of 6-halo-6-deoxy- and 6-deoxy-ascorbic acid analogues, and 3- or 4-O-alkyl ethers of ascorbic acid. As part of a program to study the effects of structural modification on vitamin C function and to provide biochemical tools for vitamin C research, we have prepared the known 6-halo-6-deoxy analogues and have initiated kinetic measurements of transport inhibition of these analogues. In addition, we have developed reactions that should provide routes to new analogues that can function as affinity labels, radiotracers, and NMR probes.