A1 Refereed original research article in a scientific journal
3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl Groups as Biodegradable Protecting Groups of Nucleoside 5 '-mono-Phosphates
Authors: Ora M, Mantyvaara A, Lonnberg H
Publisher: MDPI AG
Publication year: 2011
Journal: Molecules
Journal name in source: MOLECULES
Journal acronym: MOLECULES
Number in series: 1
Volume: 16
Issue: 1
First page : 552
Last page: 566
Number of pages: 15
ISSN: 1420-3049
DOI: https://doi.org/10.3390/molecules16010552
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/2045232
Thymidine 5`-bis[3-acetyloxy-2-cyano-2-(2-phenylethylcarbamoyl)propyl] phosphate (1) has been prepared and the removal of phosphate protecting groups by hog liver carboxyesterase (HLE) at pH 7.5 and 37 degrees C has been followed by HPLC. The first detectable intermediates are the (R(P))- and (S(P))-diastereomers of the monodeacetylated triester 14, which subsequently undergo concurrent retro-aldol condensation to diester 4 and enzyme-catalyzed hydrolysis to the fully deacetylated triester 15. The former pathway predominates, representing 90% of the overall breakdown of 14. The diester 4 undergoes the enzymatic deacetylation 700 times less readily than the triester, but gives finally thymidine 5`-monophosphate as the desired main product. To elucidate the potential toxicity of the electrophilic 2-cyano-N-(2-phenylethyl) acrylamideby-product 17 released upon the deprotection, the hydrolysis of 1 has also been studied in the presence of glutathione (GSH).
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