OXIDATION CHEMISTRY OF INDOLES

吲哚的氧化化学

• 批准号: 3281130
• 负责人: GLENN DRYHURST
• 金额: $ 11.36万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-15 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281130
• 关键词: 5 hydroxytryptophan; electrochemistry; indoles; neurotoxins; neurotransmitters; oxidation; quinones; serotonin; tryptophan

The aim of this project is to employ electrochemical and other analytical techniques to investigate the oxidation chemistry of naturally occurring or otherwise biologically significant indoles. These will include the 5-hydrosylated metabolites of tryptophan, N-methylated indoles (such as bufotenin) which are implicated in the etiology of schizophrenia and depression, and 5,6- and 5,7-dihydrosytryptamines (5,6- and 5,7-DHT) which are powerful neurotoxins. Anomalous, minor oxidation pathways of, for example, the enurotransmitter 5-hydrosytryptamine have been speculated to play a role in some mental disorders. Similarly, the neurotoxicity of 5,6- and 5,7DHT is thought to be due to reactions of their reactive autoxidation products in the CNA. Many of these indoles undergo oxidation reactions in biological systems yet virtually nothing is known about the mechanisms and products of these processes. Modern electroanalytical techniques will be used to elucidate the nature of the primary oxidation step and the identity and properties of transient intermediates. Longer lived intermediates will be further studied using spectral and chromatographic methods, particularly GC-MS and LC-MS techniques. Reaction products will be isolated and identified using a wide range of analytical techniques including column chromatography, HPLC, U.V.-vis, I.R., NMR and mass spectrometry. Evidence concerning the biological relevance of such studies will be obtained by investigating the oxidation of these indoles with various CNS enzymes and critically comparing the courses of the electrochemical and enzymatic oxidations. In vivo evaluations of the neurotoxic properties of the many new products formed by electrochemical and enzymatic oxidation are planned. Electrochemical and other analytical techniques will be used to study the interactions of the very reactive primary oxidation products of indoles (quinones, quinoneimines, methyleneimines) with nucleophiles commonly found in CNS tissue (thiols, amino acids, water). The long range goal is to develop a fundamental understanding of the oxidation chemistry of biologically significant indoles. This, in turn, could provide a basis for understanding the oxidation chemistry of such indoles in living systems which might give important insights into a chemical basis for some mental illnesses and other disease states.

该项目的目的是采用电化学和其他分析 研究天然发生或 否则生物学上意义的吲哚。 这些将包括 色氨酸，N-甲基化吲哚的5-氢糖基化代谢产物（例如 与精神分裂症的病因有关的bufotenin） 抑郁症，5,6-和5,7-二氢胺（5,6-和5,7-DHT） 是强大的神经毒素。 对于 例如，据推测，Enurotransmitter 5-Hydrosyptamine已被推测 在某些精神障碍中发挥作用。 同样，神经毒性为5,6- 5,7DHT被认为是由于其反应性自氧化的反应 CNA中的产品。 这些吲哚中的许多都经历了氧化反应 生物系统几乎尚未了解机制和 这些过程的产品。 现代的电分析技术将是 用于阐明主要氧化步骤的性质和身份 和瞬态中间体的特性。 更长的中间体将 使用光谱和色谱方法进一步研究，尤其是 GC-MS和LC-MS技术。 反应产物将被隔离，并且 使用广泛的分析技术（包括柱）确定 色谱，HPLC，U.V.-VIS，I.R.，NMR和质谱法。 证据 关于此类研究的生物学相关性，将获得 调查用各种CNS酶和 批判性比较电化学和酶促的课程 氧化。 许多许多人的神经毒性特性的体内评估 电化学和酶促氧化形成的新产品是 计划。 电化学和其他分析技术将用于 研究非常反应性的原代氧化产物的相互作用 与亲核剂 通常在中枢神经系统组织（硫醇，氨基酸，水）中发现。 远距离 目标是对氧化化学的基本了解 生物学意义的吲哚。 反过来，这可以提供基础 了解这种吲哚在生命系统中的氧化化学反应 这可能会为某些精神的化学基础提供重要的见解 疾病和其他疾病状态。