Aza Analogs of Purine Bases

The names of 2-aza analogs are derived by formal substitution of the methine group in the 2-position of the purine skeleton by a nitrogen atom (140). Since this position is substituted in some purine bases, only the aza analogs of adenine or hypoxanthine are amenable to such formal derivation. 

The systematic nomenclature used originally the term imidazo-1,2,3-triazine. The Chemical Abstracts indexes use the more accurate name imidazo[4,5-d]-Z -triazine (141). The numbering of the substituents is different in the two systems of nomenclature as may be seen in the formulas. 

Substances of this type have hitherto received little attention. One of the reasons appears to be the limited possibilities of preparation. The only known method of preparation, described by Woolley et ai./ proceeds from the derivatives of 4-aminoimidazole-5-carboxylic acid. The amide of this acid (142) is treated with nitrous acid to yield 4-hydroxyimidazo [4,5-d]-i -triazine (2-azahypoxanthine) (143), the amidine (144) yielding the 4-amino derivative (2-azaadenine) (145) under the same conditions. 2-Azahypoxanthine was probably obtained in the same way earlier but was not identified.  

When it was found later that enzymatic oxidation of 2-azaadenine yields its 8-hydroxy derivative (4-amino-6-hydroxyimidazo [4,5-d]-u-triazine), its synthesis was also achieved by the procedure already described/  

Very few data exist on the physicochemical properties of these substances. The stability of 2-azaadenine against hydrolysis with hot hydrochloric acid and on the formation of silver salts have been mentioned furthermore, their UV spectra have been published without detailed interpretation.  

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The 8-aza analogs of purine bases were the first to be studied among all the aza analogs of nucleic acid bases (as early as 1945). Before that time the chemistry of these substances had not been treated in detail from any aspect. Thus the entire chemistry of the u-triazolo [4,5-d]pyrimidines was developed only in connection with the study of antimetabolites of nucleic acid components. Therefore all the papers involved are largely of preparative character and only rarely discuss. theoretical points. 

Aza Analogs of Pyrimidine and Purine Bases of Nucleic Acids... 

An important group of antimetabolites are the aza analogs of pyrimidine and purine bases which are theoretically derived by a replacement of the methine group of a pyrimidine or purine nucleus with a nitrogen atom. This replacement represents a relatively minor alteration of the structure of these substances as it does not change the functional groups, practically preserves the molecular weight, and produces almost isosteric compounds. The replacement of the methine... 

This synthetic procedure was used without any significant changes for the preparation of the greatest number of derivatives of t -tria-zolo [4,5-d] pyrimidine. Roblin et prepared the aza analogs of the principal purine bases 8-azaguanine (151), 8-azaadenine (152), 8-azaxanthine (153), and 8-azahypoxanthine (154). By similar methods,... 

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