THE GENERATION OF ACTIVE OXYGEN SPECIES BASED ON UNIQUE REACTIVITIES OF HETEROCYCLIC N-OXIDES AND ITS APPLICATIONS

基于杂环氮氧化物独特反应活性的活性氧物质的生成及其应用

基本信息

批准号：
08672564
负责人：
SAKO Magoichi
金额：
$ 1.41万
依托单位：
GIFU PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672564/
关键词：
PYRIMIDO [5,4-G] PTERIDINE N-OXIDE HYDROXYL RADICAL DNA PHOTO-CLEAVING AGENT PYRIMIDO [3,4-D] FUROXAN FACILE SYNTHETIC METHOD NITRIC OXIDE 含窒素複素環N-オキシド光反応特性 DNA鎖切断グアノシン 8-ヒドロキシグアノシン光化学的反応性 DNA鎖切断剤活性酸素種気管支拡張作用

项目摘要

Previously, we have demonstrated that a lipophilic pyrimido [5,4-g] pteridinetetraone 5-oxide behaves as an effective oxygen-atom transfer agent to electron-rich substrates under photochemical conditions in an aprotic solvent, of which reactions proceed via a single-electron transfer process in a manner similar to that of biological monooxygenations catalyzed by cytochrome P-450, and that a hydrophilic pyrimido [5,4-g] pteridinetetraone 5-oxide generates cleanly and effectively hydroxyl radicals under the photochemical conditions in an aqueous solvent to serve as a photochemical DNA-cleaving agent.In this research project, it has been documented that the water-soluble N-oxide preferentially degradates cytidine among the employed nucleosides including 2'-deoxycytidine, adenosines and guanosines leading to cytosine in a high yield under the photochemical conditions. This fact clearly indicates that the hydrophilic pyrimido [5,4-g] pteridinetetraone 5-oxide serves as the photochemical RNA-strand cleaving agent with a high selectivity.Pyrimidofuroxans have been well established to be a useful synthon for the preparation of fused pyrimidines such as purines and pteridines which are compounds of ubiquitous natural occurrence and extreme biological importance. In this research project, a facile synthetic method for the pyrimidofuroxans has been accomplished. The method involves an oxidative intramolecular cyclization of appropriate 6-amino-5-nitropyrimidines with iodosylbenzene diacetate in the presence of lithium hydride. The pyrimidofuroxans generate effectively nitric oxide and related species in the presence of N-acylated cysteamines such as N-acetylcysteamine and glutathione under physiological conditions.

Previously, we have demonstrated that a lipophilic pyrimido [5,4-g] pteridinetetraone 5-oxide behaves as an effective oxygen-atom transfer agent to electron-rich substrates under photochemical conditions in an aprotic solvent, of which reactions proceed via a single-electron transfer process in a manner similar to that of biological monooxygenations catalyzed by cytochrome P-450, and that a亲水性嘧啶[5,4-g]孢子苯酮5-氧化物在光化学条件下在水溶液条件下以水性溶剂的形式清洁有效地产生羟基自由基，以作为光化学DNA裂解剂。在这项研究项目中，该研究已记录在水溶性n-氧化的n-氧化材料中，这些研究均具有均匀的n-氧化物效率。在光化学条件下，2'-脱氧，腺苷和鸟氨酸在高产量中导致胞嘧啶。这一事实清楚地表明，亲水性嘧啶[5,4-G]翼甲酮5-氧化物用作具有高选择性的光化学RNA裂解剂，已很好地确定了pyrimidofuroxans，可以很好地确定有用的合成，以制备像融合的双脊髓那样的质量和质量质量的质量，并且是纯种的质量和质量的质量，并且是peri的质量，并且是peri的质量和质量质量的，这是无处不在的质量。重要性。在该研究项目中，已经完成了一种用于嘧啶呋喃的轻松合成方法。该方法涉及在氢化锂存在的情况下，将适当的6-氨基-5-硝基吡啶与碘二乙酸盐氧化性分子内环化。在生理条件下，在存在N-酰基甲基甲基甲酯等N-酰基甲基甲酯和谷胱甘肽等N-酰基囊酯的情况下，嘧啶氟卫生可以有效地产生一氧化氧化物和相关物种。