6-Azauracil nucleotides

These experiments suggest that, in the presence of 6-azauracil, there is a block in the utilization of pyrimidines at the nucleotide level. Later experiments have shown that there is an inhibition of orotidylic decarboxylase... 

Very few compounds containing the 1,2,4-triazine moiety are found as natural materials, such as the pyrimido[5,4-c]-1,2,4-triazines, fervenulin (2),265 reumycin (3),265 toxoflavin (4) and MSD-92 (5).441 A large number of synthetic 1,2,4-triazines have biological activity and have been used for various purposes. Thus, 1,2,4-triazines can be considered as azapyrimidines and thus a large number of 6-azapyrimidine nucleotides and nucleosides have been prepared and their properties studied intensively, for example 6-azauracil (6), 6-azathymine(7), 6-azacytosine (8), 6-azauridine (9),442 and 6-azacytidine (10).443... 

Since 1,2,4-triazines can be considered as azapyrimidines, a great number of 6-azapyrimidine nucleotides and nucleosides have been prepared and their properties intensively studied. Most significant amongst these are 6-azauracil (1), 6-azauridine (2), 6-azathymine (3), 6-azacytosine (4) and 6-azacytidine (5). 

Uridylic acid, the nucleotide found in RNA, is formed by decarboxylation of orotidylic acid in the presence of orotidine-5 -phosphate decarboxylase, an enzyme purified from yeast. This is an irreversible reaction that has been observed in bacteria, birds, and several mammalian tissues. The antimetabolite 6-azauracil blocks orotidylic acid decarboxylase. 

Bis(trimethylsilyl) ether of 5-triflnoromethyl-6-azauracil 48 was obtained for the synthesis of the corresponding p-D-deoxyribonucleoside and nucleotide. a-Trifluoromethacrylic acid 43 has been converted with hydrogen peroxide to a,p-dihydroxy-a-trifluoromethylpropionic acid 44, which gave the hydrate of per-fluoropyruvic acid 45 on treatment with sodium periodate. The semicarbazone 46... 

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