3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl Groups as Biodegradable Protecting Groups of Nucleoside 5 '-mono-Phosphates

: Ora M, Mantyvaara A, Lonnberg H

Publisher: MDPI AG

: 2011

: Molecules

: MOLECULES

: 1

: 16

: 1

: 552

: 566

: 15

: 1420-3049

DOI: https://doi.org/10.3390/molecules16010552(external)

: https://research.utu.fi/converis/portal/Publication/2045232(external)

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).

Chemical sciences

2011 3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl groups as biodegradable protecting groups of nucleoside 5´-monophosphates.pdf