Reactions of Adenine Nucleosides with Aqueous Alkalies: Kinetic and Mechanism

Article abstract of DOI:10.1021/jo00370a013

The hydrolysis of adenosine in aqueous alkali has been studied by liquid chromatography (LC), NMR spectroscopy, and isotopic labeling techniques.The first step of the multistage reaction pathway has been shown to be a nucleophilic attack of hydroxide ion on the C8 atom with concomitant opening of the imidazole ring.The equilibrium mixture of 4-amino-5-formamido-6-(ribosylamino)pyrimidines obtained undergoes three competitive reactions, viz., intramolecular cyclization to adenine nucleosides and N⁶-ribosyladenines and degradation to nonchromophoric products, most probably via intermediary formation of 4,5-diamino-6-(ribosylamino)pyrimidines.Isomeric N⁶-ribosyladenines are further hydrolyzed to adenine and D-ribose.The rate constants for the different partial reactions have been determined at various concentrations of hydroxide ion.The mechanisms of individual steps are discussed.Comparative kinetic studies with 2'-deoxy-, 2',3'-O-isopropylidene-, and 5'-O-methyladenosine and 9-β-D-arabinofuranosyladenine and its 5'-O-methyl derivative are interpreted to indicate that the glycon moiety hydroxyl groups do not play any important role in the alkaline cleavage of adenine nucleosides.