1997 Fiscal Year Final Research Report Summary
THE GENERATION OF ACTIVE OXYGEN SPECIES BASED ON UNIQUE REACTIVITIES OF HETEROCYCLIC N-OXIDES AND ITS APPLICATIONS
| Project/Area Number |
08672564
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
医薬分子機能学
|
|---|
| Research Institution | GIFU PHARMACEUTICAL UNIVERSITY |
|---|
Principal Investigator |
SAKO Magoichi GIFU PHARMACEUTICAL UNIVERSITY,DEPARTMENT OF PUBLIC HEALTH PHARMACY,ASSOCIATED PROFESSOR, 薬学部, 講師 (10137060)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Keywords | PYRIMIDO [5,4-G] PTERIDINE N-OXIDE / HYDROXYL RADICAL / DNA PHOTO-CLEAVING AGENT / PYRIMIDO [3,4-D] FUROXAN / FACILE SYNTHETIC METHOD / NITRIC OXIDE |
|---|
| Research Abstract |
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.
|
