Aza Analogs of Pyrimidine Bases

The names of these compounds as aza analogs were coined in the same way as those of the 6-aza analogs employing the frequently used numbering of uracil (1). This nomenclature is most often used for the principal aza analogs of pyrimidine bases (e.g., 5-azauracil) it is rarely used for further systematic derivatives. 

According to the triazine nomenclature, 5-azauracil is 2,4-dioxo-l,2,3,4-tetrahydro-l,3,5-triazine (2). The subject index of Chemical Abstracts prefers s-triazine-2,4(lH,3H)-dione. Furthermore, some authors use a name derived from the lactim structure, 2,4-dihydroxy-s-triazine (3). The numbering of the substituents is the same for all these types of nomenclature. 

4-tetrahydro-s-triazine (2) is that of allantoxaidine which had been heretofore formulated as iminohydantoin (6) on the basis of a suggestion of Ponomarev and subsequent work of Biltz and Robl. Allantoxaidine is formed by decarboxylation of oxonic (allantox-anic) acid (5) which is the product of alkaline oxidation of uric acid (4) with hydrogen peroxide. This reaction was studied in detail by several authors and was expressed as follows  

Its oxidation to cyanuric acid (10) and its hydrolysis to biuret (11) and formic acid is also in agreement with the new formulation of allantoxaidine as a triazine derivative. A very strained explanation would be required to make these reactions conform to the original structure. 

All these findings, as well as the similarity of UV spectra - caused dioxotetrahydrotriazine to be classified as the simplest member of the formerly known 6-substituted derivatives. These derivatives are not interesting in connection with the analogs of natural pyrimidine bases and have been reviewed elsewhere. The structure of allantoxaidine and its appurtenance to the triazine series have been recently demonstrated by its unequivocal synthesis. 

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The chemistry of the 6-aza analogs of pyrimidine bases which has been developed from the biochemical aspect since about 1956 was based on work reported in relatively numerous older papers. In spite of the fact that 6-azauracil was prepared only in 1947 and suitable syntheses were described only quite recently, substances of this type and methods of their preparation had been known for a long time. The chemistry of 6-aza analogs of pyrimidine bases is therefore relatively closely linked with the chemistry of the 1,2,4-triazine derivatives. 

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... 

In all types of nomenclature based on triazine the numbering of the substituents is shifted by one as compared with the nomenclature of 6-aza analogs of pyrimidines. 

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. 

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