CHEMISTRY OF PURINES AND PYRIMIDINES 93 



compounds related to the pyrimidine moiety of thiamine, certain of the derivatives 

 possessing a substituent such as — CH3 , — CI, or — H at carbon 2 which is not capable 

 of protopic change (a change such as 



+ H^ 



H 



etc.) do not show the instability associated with the corresponding uracil or cytosine 

 derivatives described above. For example, a cjuantitative yield of 2-methyl-5-amino- 

 methyl-6(4)-hydroxypyrimidine is obtained when the 5-urethanomethylpyrimidine is 

 heated at 100°C. for 2 hours with concentrated HCl;'"' the aminomethyl group is con- 

 verted to hydroxymethj-l upon nitrous acid treatment for 7 hours at 100°C.'^ The 

 hydroxymethj'l group of 4-methyl-5-hydroxymethyl-6-aminoi)yrimidine persists after 

 heating its 2-chloro derivative with zinc in water at 100° for 7 hours (no yields are cited, 

 however).'"'' Also, 2-methyl-5-bromomethyl-6-aminopyrimidine, in acid or neutral 

 solution, withstands several treatments in the autoclave'"^ (cf . Endicott and Johnson*^ 

 and Schmedes'*). 



The simple replacement of a hydrogen atom of the stably-bound methyl group of 

 5-methyl-uracil or -cytosine by hydroxyl or amino (or chloro) gives rise to compounds 

 possessing a carbon-carbon linkage which is unstable towards hot water or mineral 

 acid, but not (in the case of 5-hydroxymethylcytosine (XV)) towards hot formic acid 

 (which is a reducing agent). As yet, no theoretical explanation is available for this 

 phenomenon and any explanation that is put forward must take into account the 

 stalMlity of the other derivatives mentioned above. 



h. Purines and Pyrimidines in Other Biological Sources 



A detailed catalog listing the widespread natural distribution of purines 

 and pyrimidines has been compiled.'"^ For other listings, the general ref- 

 erences at the end of this chapter may be consulted. Because of this excel- 

 lent reference literature, greater emphasis will be given to more recent 

 developments. 



Purine (C5H4N4), the parent member of the series, "^^ has recently been 

 isolated as a 9-D-riboside ("Nebularine") from a mushroom.'"*'"" Nebu- 

 larine, the detailed structure of which has been established by synthesis as 



i«3 A. R. Todd, F. Bergel, H. 1.. Fraenkel-Conrat, and A. Jacob, J. Chem. Soc. 1936, 



1601. 

 1" H. Andersag and K. Westphal, Ber. 70, 2035 (1937). 



"OS W. J. Robbins and F. Kavanagh, Proc. Natl. Acad. Set. U. S. 24, 141 (1938). 

 los C. Wehmer and M. Hadders, in "Handbuch der Pflanzenanalyse" (G. Klein, ed.), 



Vol. 4, p. 405. Springer, Vienna, 1933. 

 '" Beilstein, 26, 354 (1937). 

 '08 L. Ehrenberg, H. Hedstrom, N. Lofgren, and B. Takman, Svensk Kern. Tid. 58, 269 



(1946). 

 '09 N. Lofgren, B. Takman and H. Hedstrom, Svensk Farm. Tidskr. 53, 321 (1949). 

 "" N. Lofgren and B. Liining, Acta Chem. Scand. 7, 15 (1953). 



