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）是人类健康的饮食必需品， 多种酶促反应的电子供体，充当 抗氧化剂，并与宿主防御机制、内分泌 功能和视觉过程（晶状体）。 最近重新燃起人们的兴趣 抗坏血酸的生物化学是由于认识到 关于维生素的浓度知之甚少 这几个角色的最佳运作所必需的。 在这种情况下 酶促反应的最佳过程速率定义为 使反应达到 Vmax 而无毒性的浓度。 作为确定这些浓度的计划的一部分，原位动力学 已对某些与维生素 C 相关的物质进行了测量 反应。 除了检查维生素的功能作用外 C，高效运输机制的最新特征 跨细胞膜转运维生素 C 强调了 维生素对生物过程的重要性。 动力学 6-脱氧-6-卤代抗坏血酸转运抑制的测量 类似物清楚地证明了单独途径的存在 用于抗坏血酸和脱氢抗坏血酸的易位。 我们 合成了放射性标记的 6-脱氧-6-碘抗坏血酸作为工具 研究抗坏血酸转运系统的更多细节。 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。 这个类似物被用来 制备2-脱氧-2-卤代抗坏血酸，包括 2-脱氧-2-氟-抗坏血酸，等排和等极性， 不可氧化的类似物。 环状半缩酮形式 还制备了2,2-二氟-2-脱氧抗坏血酸，其结构如下 对应于脱氢抗坏血酸的环状半缩酮形式。 这 这些新化合物的生物学特性正在研究中。