A1 Refereed original research article in a scientific journal

Chemical and enzymatic stability of amino acid derived phosphoramidates of antiviral nucleoside 5 '-monophosphates bearing a biodegradable protecting group




AuthorsLeisvuori A, Aiba Y, Lönnberg T, Poijärvi-Virta P, Blatt L, Beigelman L, Lönnberg H

PublisherROYAL SOC CHEMISTRY

Publication year2010

JournalOrganic and Biomolecular Chemistry

Journal name in sourceORGANIC & BIOMOLECULAR CHEMISTRY

Journal acronymORG BIOMOL CHEM

Volume8

Issue9

First page 2131

Last page2141

Number of pages11

ISSN1477-0520

DOIhttps://doi.org/10.1039/b924321f


Abstract
Ribavirin and 2'-O-methylcytidine 5'-phosphoramidates derived from L-alanine methyl ester bearing either an O-phenyl or a biodegradable O-[3-(acetyloxy)-2,2-bis(ethoxycarbonyl) propyl] or O-[3-(acetyloxymethoxy)-2,2-bis(ethoxycarbonyl) propyl] protecting group were prepared. The kinetics of the deprotection of these pro-drugs by porcine liver esterase and by a whole cell extract of human prostate carcinoma was studied by HPLC-ESI-MS/MS. The 3-(acetyloxymethoxy)-2,2-bis(ethoxycarbonyl) propyl and 3-(acetyloxy)-2,2-bis(ethoxycarbonyl) propyl groups were readily removed releasing the L-alanine methyl ester phosphoramidate nucleotide, the deprotection of the 3-(acetyloxymethoxy) derivative being approximately 20 times faster. The chemical stability of the 2'-O-methylcytidine pro-drugs was additionally determined over a pH range from 7.5 to 10.


Research Areas



Last updated on 2024-26-11 at 20:28