SYNTHESIS AND BIOCHEMISTRY OF ASCORBIC ACID ANALOGUES

抗坏血酸类似物的合成及生物化学

• 批准号: 6161951
• 负责人: K L KIRK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161951
• 关键词: ascorbate; biochemistry; biological transport; chemical kinetics; chemical structure function; chemical synthesis; intermolecular interaction; membrane transport proteins; nutrition related tag; transport inhibitor; vitamin analog; vitamin metabolism

Ascorbic acid (vitamin C), a dietary requirement for human health, is an electron donor for several enzymatic reactions, 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 measurements of transport inhibition of 6-deoxy-6-haloascorbic acid analogues have clearly demonstrated the presence of separate pathways for the translocation of ascorbic acid and dehydroascorbic acid. We have synthesized radiolabelled 6-deoxy-6-iodoascorbic acid as a tool for studying additional details of the ascorbic acid transport system. To investigate the importance of the 2-hydroxyl group on ascorbic acid activity, we prepared 2-deoxy-ascorbic acid. This analogue was used to prepare 2-deoxy-2-halo ascorbic acids, including 2-deoxy-2-fluoro-ascorbic acid, an isosteric and isopolar, non-oxidizable, analogue. The cyclic hemiketal form of 2,2-difluoro-2-deoxyascorbic acid also was prepared, a structure which corresponds to the cyclic hemiketal form of dehydroascrobic acid. The biological properties of these new compounds are under investigation.

抗坏血酸（维生素C）是人体健康的膳食必需品， 几种酶促反应的电子供体， 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 6-脱氧-6-卤代抗坏血酸的转运抑制的测量 类似物已经清楚地证明了不同途径的存在 用于抗坏血酸和脱氢抗坏血酸的移位。 我们 已经合成了放射性标记的6-脱氧-6-碘抗坏血酸， 研究抗坏血酸转运系统的其他细节。 到 研究2-羟基对抗坏血酸的重要性 活性，我们制备了2-脱氧抗坏血酸。 这种类似物用于 制备2-脱氧-2-卤代抗坏血酸，包括 2-脱氧-2-氟-抗坏血酸，电子等排和等极性， 不可氧化的类似物。 的环状半缩酮形式 还制备了2，2-二氟-2-脱氧抗坏血酸，其结构 对应于脱氢抗坏血酸的环状半缩酮形式。 的 这些新化合物的生物学特性正在研究中。