Acid-Catalyzed Hydrolysis of 2-Amino-9-(α-D-Ribofuranosyl)-purine and its Acyclo and 2-Methyl Analogues: Competition Between Depurination and Opening of the Imidazole Ring

Hydrolytic decomposition of 2-amino- and 2-methyl-9-(B-D-ribofuranosyl)purines, 2-methyladenosine, 2-amino-7-and -9-(2-hydroxyethoxymethyl)purines and 9-ethoxymethyl-purine has been followed by HPLC under acidic conditions. 2-Methyladenosine undergoes depurination over the entire acidity range studied (pH 4.7 to Ho -0.7). The other compounds are depurinated only at high hydronium ion concentrations, while under mildly acidic conditions the imidazole ring is opened to give 2-substituted 4-amino-5-formamidopyrimidine. The latter compound finally undergoes competitive deformylation to 4,5-diaminopyrimidine and cyclization to 2-substituted purine. The mechanism of the imidazole ring opening is discussed on the basis of the pH-rate profiles and structural effects.