A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
The chemical stability of S-(2-acylthioethyl) and S-acyloxymethyl protected thymidylyl-3 ',5 '-thymidine phosphoromonothiolates and their deacylation products in aqueous solution
Tekijät: Poijarvi P, Oivanen M, Lonnberg H
Kustantaja: MARCEL DEKKER INC
Julkaisuvuosi: 2001
Lehti:: Nucleosides, Nucleotides and Nucleic Acids
Tietokannassa oleva lehden nimi: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
Lehden akronyymi: NUCLEOS NUCLEOT NUCL
Vuosikerta: 20
Numero: 1-2
Aloitussivu: 77
Lopetussivu: 91
Sivujen määrä: 15
ISSN: 1525-7770
DOI: https://doi.org/10.1081/NCN-100001438
Tiivistelmä
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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