Next Article in Journal
Homopolymerization of Ethylene, 1-Hexene, Styrene and Copolymerization of Styrene With 1,3-Cyclohexadiene Using (h5-Tetramethylcyclopentadienyl)dimethylsilyl(N-Ar’)amido-TiCl2/MAO (Ar’=6-(2-(Diethylboryl)phenyl)pyrid-2-yl, Biphen-3-yl)
Next Article in Special Issue
Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment
Previous Article in Journal
Antimicrobial Activity of Diterpenes from Viguiera arenaria against Endodontic Bacteria
Previous Article in Special Issue
Design and Synthesis of Anti-MRSA Benzimidazolylbenzene-sulfonamides. QSAR Studies for Prediction of Antibacterial Activity
Article Menu

Export Article

Open AccessArticle
Molecules 2011, 16(1), 552-566;

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

Department of Chemistry, University of Turku, FIN-20014 Turku, Finland
Author to whom correspondence should be addressed.
Received: 22 November 2010 / Revised: 30 December 2010 / Accepted: 13 January 2011 / Published: 14 January 2011
(This article belongs to the Special Issue Prodrugs)
Full-Text   |   PDF [533 KB, uploaded 18 June 2014]   |  


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 °C has been followed by HPLC. The first detectable intermediates are the (RP)- and (SP)-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). View Full-Text
Keywords: prodrug; nucleotide; biodegradable; protecting group prodrug; nucleotide; biodegradable; protecting group

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Ora, M.; Mäntyvaara, A.; Lönnberg, H. 3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl Groups as Biodegradable Protecting Groups of Nucleoside 5´-mono-Phosphates. Molecules 2011, 16, 552-566.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top