512 R. E. HANDSCHUMACHER AND A. D. WELCH 



been interpreted as the result of multiple blockade of the synthesis of thymine deriva- 

 tives de novo and the utilization of preformed thymine, further experiments will be 

 required to establish this point. 



4. AZAPYRIMIDIKTES 



Replacement in the natural pyrimidines of one of the ring carbons and 

 its associated hydrogen with the isosteric atom, nitrogen, results in series 

 of symmetric and asymmetric triazines of some biological interest. The 

 symmetric triazine derivative, oxonic acid [6-carboxy-s(/ra-triazine-2,4 

 (lH,3H)-dione], an analog of orotic acid, is prepared as a degradation 

 product of uric acid 455, 456 ; it possesses a certain amount of anti-pyrimidine 

 activity. 457 The corresponding uracil analog, oxaidin [sf/ra-triazine-2,4 

 (lH,3H-dione], has also been prepared 455 456 and found to inhibit the 

 growth of adenocarcinoma-755. 457 



Of greater interest has been the series of asymmetric triazines represented 

 by 4(6)-azauracil [as-triazine-3,5(2H,4H)-dione] (XV), 4(6)-azacytosine, 

 and 4(6)-azathymine (XVI). The synthesis of azauracil was described in 

 1947458. however, better methods of preparation, via the semicarbazone of 

 oxomalonic acid, have been reported, 459460 and a simplified procedure, 

 which utilizes chloral hydrate in the formation of the semicarbazone of 

 glyoxylic acid, is now used. 461 Azacytosine has been prepared from azaura- 

 cil, using an intermediate formed with the aid of phosphorus pentasulfide, 

 while azathymine was formed from the semicarbazone of pyruvic acid. 460 



O 



The uracil analog antagonized the growth of microorganisms not only 

 when they were supplied with pyrimidines exogenously, but also when 

 they synthesized their own de novo; indeed, growth inhibition was most 



466 H. Biltz, Ber. 46, 3410 (1913). 



486 E. S. Canellakis and P. P. Cohen, J. Biol. Chem. 213, 379 (1955). 



467 S. Bieber, G. B. Elion, H. C. Nathan, and G. H. Hitchings, Proc. Am. Assoc. Can- 

 cer Research 2, 188 (1957). 



488 W. Seibert, Ber. 80, 494 (1947). 



459 R. B. Barlow and A. D. Welch, J. Am. Chem. Soc. 78, 1258 (1956). 



460 E. A. Falco, E. Pappas, and G. H. Hitchings, J. Am. Chem. Soc. 78, 1938 (1956). 



461 P. K. Chang and T. L. V. Ulbricht, J. Am. Chem. Soc. 80, 976 (1958). 



