ADDITIONAL EVIDENCE FOR THE EXCEPTIONAL MECHANISM OF THE ACID-CATALYZED HYDROLYSIS OF 4-OXOPYRIMIDINE NUCLEOSIDES - HYDROLYSIS OF 1-(1-ALKOXYALKYL)URACILS, SECONUCLEOSIDES, 3'-C-ALKYL NUCLEOSIDES AND NUCLEOSIDE 3',5'-CYCLIC MONOPHOSPHATES

The rate constants for the acid-catalysed hydrolysis of 1-(1-alkoxyeth yl)uracils and 1-alkoxymethyluracils have been determined. With both s eries of compounds, the hydrolysis rate is rather insensitive to the p olar nature of the alkoxy group, in striking contrast with the hydroly sis of the corresponding analogues of adenine;and cytosine nucleosides , which react via rate-limiting formation of an oxocarbenium ion inter mediate. Furthermore, it has been shown that the 3',5'-cyclic monophos phates of thymidine and uridine undergo the hydrolysis of the N-glycos idic bond 760 and 260 times as fast as their parent nucleosides. while the cyclic monophosphates of 2'-deoxyadenosine and adenosine are depu rinated much more slowly than the corresponding nucleosides. On this b asis it is suggested that 4-oxopyrimidine nucleosides are hydrolysed b y opening of the sugar ring. To obtain further evidence for this excep tional mechanism, comparative kinetic measurements with some seco- and 3'-C-alkyl nucleosides of uracil and adenine have been carried out.