76 D. SHUGAR 



even more puzzling by the observation that there is no evidence of reversi- 

 bility following irradiation in buffered medium. 39 ' 141 



The differences in behavior between cytosine and 3-methylcytosine on 

 the one hand, and nucleosides and nucleotides of cytosine on the other are 

 indeed striking. The quantum yields for the latter are approximately one 

 order of magnitude greater at neutral pH, while the degree of reversibility 

 they exhibit varies from 90-100% after complete photodecomposition. For 

 cytosine the rate of the reverse reaction is considerably lower, while the 

 degree of reversibility decreases with increasing formation of the photo- 

 product. 



Since the behavior of 3-methylcytosine is similar to that of cytosine, it 

 follows that the difference in behavior between cytosine glycosides and 

 3-methylcytosine is not due to substitution on the N 3 ring nitrogen but must 

 result from some interaction between the pyrimidine and carbohydrate 

 rings; and this is clearly placed in evidence by an examination of the rate 

 of the forward reaction for the various cytidylic acid isomers, as well as for 

 the individual isomers in the alkaline pH range (Table III) where dissocia- 

 tion of the carbohydrate hydroxyls is revealed by modifications in spectra. 66 

 On the basis of these results it has been postulated that the increased facil- 

 ity of reversible photodecomposition of cytosine nucleosides, as compared 

 to 3-methylcytosine, is due to intramolecular hydrogen bonding between 

 the 2-carbonyl of the aromatic ring and one of the sugar hydroxyls 39 ' 140 ' 

 hi, 149. tj^ thi s i s stereochemical^ possible is shown by the synthesis of 

 c^/cZo-nucleosides. 151 • 152 The photochemical data appear to indicate involve- 

 ment largely of the 5'-hydroxyl, but not necessarily to the exclusion of the 

 others 39, 149 ; the 2'-hydroxyl has been suggested as that principally involved, 

 on the basis of spectral evidence. 153 



c. 4~ o,nd 5 -Substituted Derivatives 



There are a number of pyrimidine derivatives which do not form rever- 

 sible photoproducts, 39 ' l4 °- u -- 148 such as orotic acid, thymine and its nucleo- 

 sides and nucleotides, barbituric acid (see above) and methylated barbituric 

 acids, 2-thiouracil, 2,4-diethoxypyrimidine, etc. On the other hand there 

 are compounds such as 2-ethoxyuracil which on irradiation give rise to 

 relatively stable, new pyrimidine derivatives which do not revert to the 

 parent compound; and 2-methoxy cytosine, the photoproduct of which ex- 

 hibits an absorption spectrum incompatible with the existence of a 4,5 

 saturated bond, but which largely reverts to the original compound on 



151 A. M. Michelson and A. R. Todd, J. Chem. Soc. p. 816 (1955). 



162 A. M. Michelson, Tetrahedron 2, 333 (1958). 



163 J. J. Fox, J. F. Codington, N. Yung, L. Kaplan, and J. O. Lampen, J. Am. 

 Chem. Soc. 80, 5155 (1958). 



