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



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

Publisher: ROYAL SOC CHEMISTRY

: 2010

: Organic and Biomolecular Chemistry

: ORGANIC & BIOMOLECULAR CHEMISTRY

: ORG BIOMOL CHEM

: 8

: 9

: 2131

: 2141

: 11

: 1477-0520

DOI: https://doi.org/10.1039/b924321f


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.



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