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。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。 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。 分子模拟证实了2，2-二氟-2-脱氧抗坏血酸的环状半缩酮形式与脱氢抗坏血酸的环状半缩酮形式的相似性。 这些类似物的运输特性，以及它们对glutarodoxin的影响，酶，减少脱氧抗坏血酸抗坏血酸，正在研究中。 6-卤代-6-脱氧-L-抗坏血酸类似物在氧化时不能形成类似的环状半缩醛。 如果环状结构是由脱氢抗坏血酸转运蛋白转运的形式，则氧化的6-卤代类似物不应易位。 正在进行研究，以审查这一问题。基于三氟甲磺酸酯前体的亲核氟化物取代，正在研究[18-F]-6-脱氧-6-氟-L-抗坏血酸的方法。

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. We have 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 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. 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. Molecular modeling confirms the similarity of the cyclic hemiketal form of 2,2-difluoro-2-deoxyascorbic acid also the cyclic hemiketal form of dehydroascrobic acid. Transport properties of these analogues, as well as their effects on glutarodoxin, the enzyme that reduces deoxyascorbic acid to ascorbic acid, are being investigated. 6-Halo-6-deoxy-L-ascorbic analolgs, when oxidized, are unable to form a similar cyclic hemiacetal. If the cyclic structure is the form that is transported by the dehydroasorbate transporter, the oxidiazed 6-halo analogs should not be translocated. Studies to examine this question are in progress. Approaches to [18-F]-6-deoxy-6-fluoro-L-ascorbic acid are being investigated based on nucleophilic fluoride substitution of a triflate precursor.