152 



J. BADDILEY 



■0 



AcO OAc 



AcHNf'^ 



N 

 AcHN 



N 



N. 



NH, 



The above syntheses are moderately convenient and were valuable for 

 demonstrating the jS-configuration of the glycosidic linkage in the natural 

 nucleosides. However, they do not in themselves establish the position of 

 attachment of sugar and purine. An alternative synthesis, although less 

 convenient, is unambiguous and may be regarded as a modification of a 

 general synthesis for purines and their 9-substituted derivatives.^^- ** In 

 the scheme described here the starting point is a substituted 4 , 6-diamino- 

 pyrimidine. For the synthesis of purine glycosides a 4-amino-6-glycosyl- 

 aminopyrimidine is employed. These may be prepared by acid-catalyzed 

 condensation of a diaminopyrimidine with a sugar in alcoholic solution. ^^ 

 A 2', 4'- or 2',5'-dichlorophenylazo group is introduced at the 5-position in 

 the pyrimidine ring by coupling in neutral solution with the appropriate 

 diazonium salt.^" The hydroxyl groups in the sugar residue are usually 

 acetylated at this stage and the azo group reduced to amino with hydrogen 

 and a nickel catalyst. The resulting acetylated 4 , 5-diamino-6-glycosyl- 

 aminopyrimidine is converted into the corresponding 5-thioformamidopy- 

 rimidine by reaction with dithioformic acid or its sodium salt. Cyclization 

 of the thioformamido compound in pyridine may proceed in two directions, 

 giving the acetylated 9-glycosyladenine or 6-glycosylaminopurine, which 

 can be separated before or after deacetylation.'^^ 



The yield of purine glycoside obtained in the above synthesis is improved 

 by cyclization of the thioformamido compound with alcoholic alkoxide 

 solutions. Under these conditions unacetylated glycosylpyrimidines give 

 exclusively the 9-glycosylpurines whereas the acetylated derivatives yield 



" J. Baddiley, B. Lythgoe, D. McNeil, and A. R. Todd, J. Chem. Soc, 1943, 383. 



68 J. Baddiley, B. Lythgoe, and A. R. Todd, J. Chem. Soc. 1943, 386. 



69 J. Baddiley, B. Lythgoe, and A. R. Todd, J. Chem. SOc. 1943, 571. 

 '» B. Lythgoe, A. R. Todd, and A. Topham, /. Chem. Soc. 1944, 315. 

 " J. Baddiley, B. Lythgoe, and A. R. Todd, /. Chem. Soc. 1944, 318. 



