A1 Refereed original research article in a scientific journal
The chemical stability of S-(2-acylthioethyl) and S-acyloxymethyl protected thymidylyl-3 ',5 '-thymidine phosphoromonothiolates and their deacylation products in aqueous solution
Authors: Poijarvi P, Oivanen M, Lonnberg H
Publisher: MARCEL DEKKER INC
Publication year: 2001
Journal:: Nucleosides, Nucleotides and Nucleic Acids
Journal name in source: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
Journal acronym: NUCLEOS NUCLEOT NUCL
Volume: 20
Issue: 1-2
First page : 77
Last page: 91
Number of pages: 15
ISSN: 1525-7770
DOI: https://doi.org/10.1081/NCN-100001438
Abstract
The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2-pivaloylthioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected Rp and Sp phosphoromonothiolates of 3',5'-TpT has been studied. Rather unexpectedly, an intramolecular hydroxide ion catalyzed acetyl migration from the protecting group to the nucleoside 3'- and 5'-hydroxy functions was found to compete with the intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the phosphorus atom of la,b and 3a,b, respectively. With the S-pivaloylthioethyl derivative 2a,b no such reaction took place. Additionally, the kinetics of the cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic deacylation of 1a,b and 2a,b, were studied as a function of pH.
The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2-pivaloylthioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected Rp and Sp phosphoromonothiolates of 3',5'-TpT has been studied. Rather unexpectedly, an intramolecular hydroxide ion catalyzed acetyl migration from the protecting group to the nucleoside 3'- and 5'-hydroxy functions was found to compete with the intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the phosphorus atom of la,b and 3a,b, respectively. With the S-pivaloylthioethyl derivative 2a,b no such reaction took place. Additionally, the kinetics of the cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic deacylation of 1a,b and 2a,b, were studied as a function of pH.
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