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
M. Oivanen et al., 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, Perkin transactions. 2, (2), 1994, pp. 309-314
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.