A1 Refereed original research article in a scientific journal
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
Authors: OIVANEN M, RAJAMAKI M, VARILA J, HOVINEN J, MIKHAILOV S, LONNBERG H
Publisher: ROYAL SOC CHEMISTRY
Publication year: 1994
Journal:: Royal Society of Chemistry. Journal: Perkin Transactions 2
Journal name in source: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
Journal acronym: J CHEM SOC PERK T 2
Issue: 2
First page : 309
Last page: 314
Number of pages: 6
ISSN: 0300-9580
DOI: https://doi.org/10.1039/p29940000309
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.
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.
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