Additional evidence for the exceptional mechanism of the acid-catalysed hydrolysis of 4-oxopyrimidine nucleosides: hydrolysis of 1-(1-alkoxyalkyl)uracils, seconucleosides, 3′-C-alkyl nucleosides and nucleoside 3′,5′-cyclic monophosphates

Abstract

The rate constants for the acid-catalysed hydrolysis of 1-(1 -alkoxyethyl)uracils and 1-alkoxymethyluracils have been determined. With both series of compounds, the hydrolysis rate is rather insensitive to the polar nature of the alkoxy group, in striking contrast with the hydrolysis of the corresponding analogues of adenine and cytosine nucleosides, which react via rate-limiting formation of an oxocarbenium ion intermediate. Furthermore, it has been shown that the 3′,5′-cyclic monophosphates of thymidine and uridine undergo the hydrolysis of the N-glycosidic bond 760 and 260 times as fast as their parent nucleosides, while the cyclic monophosphates of 2′-deoxyadenosine and adenosine are depurinated much more slowly than the corresponding nucleosides. On this basis it is suggested that 4-oxopyrimidine nucleosides are hydrolysed by opening of the sugar ring. To obtain further evidence for this exceptional mechanism, comparative kinetic measurements with some seco- and 3′-C-alkyl nucleosides of uracil and adenine have been carried out.