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.

此前，我们已经证明，在非质子溶剂中的光化学条件下，亲脂性嘧啶并[5,4-g]蝶啶四酮5-氧化物可作为有效的氧原子转移剂至富电子底物，其反应通过单-电子转移过程的方式类似于细胞色素 P-450 催化的生物单氧化作用，并且是亲水性嘧啶[5,4-g]蝶啶四酮 5-氧化物在水性溶剂中的光化学条件下干净有效地产生羟基自由基，用作光化学 DNA 切割剂。在该研究项目中，已记录水溶性 N-氧化物优先降解胞苷中的胞苷。使用核苷，包括2'-脱氧胞苷、腺苷和鸟苷，在光化学条件下以高产率产生胞嘧啶。这一事实清楚地表明，亲水性嘧啶并[5,4-g]蝶啶四酮5-氧化物可作为具有高选择性的光化学RNA链切割剂。嘧啶呋喃氧烷已被充分证明是一种有用的合成子，可用于制备融合嘧啶，例如例如嘌呤和蝶啶，它们是天然存在且具有极其重要生物学意义的化合物。在本研究项目中，完成了嘧啶呋喃酮的简便合成方法。该方法涉及适当的6-氨基-5-硝基嘧啶与碘酰苯二乙酸酯在氢化锂存在下的氧化分子内环化。在生理条件下，在N-酰化半胱胺如N-乙酰半胱胺和谷胱甘肽存在下，嘧啶呋喃氧烷有效地产生一氧化氮和相关物质。