5-Cyanoamino-4-Imidazolecarboxamide and Nitrosative Guanine Deamination: Experimental Evidence for Pyrimidine Ring-Opening during Deamination

Abstract

5-Cyanoamino-4-imidazolecarboxamide 4a (R = CH2-O-CH2-CH2-OH) has been synthesized, purified, and fully characterized by MS, MS/MS, HRMS, IR spectroscopy, and by 1H and 13C NMR spectroscopy. It is shown that cyclization of 4a yields the guanine 6a and the isoguanine 12a. Our findings provide experimental evidence in support of our hypothesis that the formation of oxanine and xanthine in nitrosative guanine deamination may proceed via pyrimidine ring-opened intermediates. The observed formation of 6a from the amide 4 (XH2 = NH2) shows that, in analogy, oxanine can be formed from 3 (XH = OH). The formation of 12a from 4a reveals for the first time the possibility that oxanine might be formed by a second pathway that involves electrocyclic reaction of 3. Finally, the new chemistry suggests the possibility for a new dG-to-dG cross-link.

Department(s)

Chemistry

Keywords and Phrases

5 Cyanoamino 4 Imidazolecarboxamide; Guanine Derivative; Imidazolecarboxamide; Unclassified Drug; Cyclization; Deamination; High Performance Liquid Chromatography; Proton Nuclear Magnetic Resonance; Reaction Analysis; Ring Opening; Synthesis; Amides; Amines; Guanine; Imidazoles; Nitriles

International Standard Serial Number (ISSN)

0002-7863; 1520-5126

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2004 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Mar 2004

PubMed ID

14982409

Link to Full Text

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