CHEMISTRY OF PURINES AND PYRIMIDINES 135 



hydrochloride of this imidazole is heated with formamide at 185°, a good 

 yield of hypoxanthine is obtained; formylation yields 4-formamido-5- 

 imidazolecarboxamide, which in turn cyclizes to hypoxanthine by boiling 

 in dilute bicarbonate solution.^^- 



The dihydrochloride of 4-amino-5-imidazolecarboxamidine, prepared by 

 the strong acid hydrolysis of adenine^*^^ or from malononitrile,''^^ gives 

 isoguanine upon fusion with urea or reaction with phosgene.^"^ ■'^^^ Adenine 

 is obtained in 80 % yield when the above carboxamidine is formylated and 

 the formyl derivative is cyclized in dilute bicarbonate solution.^^^ 'phis re- 

 action has been adapted for the preparation (in 61 % yield) of 2-C'^-ade- 

 nine:^^* 



NH2 NH2 NH 



C 



HCOOH HN 



OH 



_ KHCO3 



H— C*=N 



H 



4-Amino-5-imidazole- 4-Formamido-5-imidazole- 



carboxamidine carboxamide (enol form) 



Addendum 



A new anti tubercular antibiotic, amicetin (C29H44N6O9), obtained from 

 Streptomyces, has been found to contain, in part, cytosine, p-aminobenzoic 

 acid, and dexiro-D-methylserine.'*** 



An inhibitor of S. faecalis, 8-aza-6-mercaptopurine has been prepared by 

 the direct thiation of 8-azahypoxan thine with P2S5 in boiling pyridine. ^^® 



Further studies on the anti-tumor activity of 6-mercaptopurine have 

 been carried out.''" Of 45 children with acute leukemia, treatment with 

 this drug has produced^^* good remission in 15 and partial remission in 10. 



The inhibitor 2-thiouracil-^^ is incorporated into the ribonucleic acid of 



"^ A. R. P. Paterson and S. H. Zbarsky, /. Am. Chein. Soc. 75, 5753 (1953). 



«5 E. H. Flynn, J. VV. Hinman, E. L. Caron, and D. O. Woolf , Jr., /. Am. Chem. Soc. 75, 



5867 (1953). 

 «« C. T. Bahner, B. Stump, and M. E. Brown, /. Am. Chem. Soc. 75, 6301 (1953). 

 *" D. A. Clarke, F. S. Philips, S. S. Sternberg, C. C. Stock, G. B. Elion, and G. H. 



Hitchings, Cancer Research 13, 593 (1953). 

 ^58 J. H. Burchenal, M. L. Murphy, R. R. Ellison, M. P. Sykes, T. C. Tan, L. A. Leone, 



D. A. Karnofsky, L. F. Graver, H. W. Dargeon, and C. P. Rhoads, Blood 8, 965 



(1953). 



