dc.creator | Manta, S. | en |
dc.creator | Tsoukala, E. | en |
dc.creator | Tzioumaki, N. | en |
dc.creator | Kiritsis, C. | en |
dc.creator | Balzarini, J. | en |
dc.creator | Komiotis, D. | en |
dc.date.accessioned | 2015-11-23T10:38:48Z | |
dc.date.available | 2015-11-23T10:38:48Z | |
dc.date.issued | 2010 | |
dc.identifier | 10.1016/j.bioorg.2009.11.001 | |
dc.identifier.issn | 0045-2068 | |
dc.identifier.uri | http://hdl.handle.net/11615/30671 | |
dc.description.abstract | The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-D-glucopyranosyl nucleosides of 5-fluorouracil (6a), N-6-benzoyl adenine (6b), uracil (6c), thymine (6d) and N-4-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regioselective 2'-O-deacylation afforded the partially acetylated dideoxynucleoside analogues of 5-fluorouracil (5a) and N-6-benzoyl adenine (5b), respectively. Direct oxidation of the free hydroxyl group at the 2'-position of 5a,b, with simultaneous elimination reaction of the beta-acetoxyl group, afforded the desired unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-glucopyranosyl derivatives 6a,b. Compounds c-e were used as starting materials for the synthesis of the dideoxy unsaturated carbonyl nucleosides of uracil (6c), thymine (6d) and N4-benzoyl cytosine (6e). Similarly a protection-selective deprotection sequence followed by oxidation of the free hydroxyl group at the 2'-position of the dideoxy benzoylated analogues 9c-e with simultaneous elimination reaction of the p-benzoyl group, gave the desired nucleosides 6c-e. None of the compounds was inhibitory to a broad spectrum of DNA and RNA viruses at subtoxic concentrations. The 5-fluorouracil derivative 6a was more cytostatic (50% inhibitory concentration ranging between 0.2 and 12 mu M) than the other compounds. (C) 2009 Elsevier Inc. All rights reserved. | en |
dc.source | Bioorganic Chemistry | en |
dc.source.uri | <Go to ISI>://WOS:000277377600008 | |
dc.subject | Unsaturated dideoxy fluoro ketonucleosides | en |
dc.subject | beta-Elimination reaction | en |
dc.subject | Antitumor activity | en |
dc.subject | FLUORO-KETOPYRANOSYL NUCLEOSIDES | en |
dc.subject | BIOLOGICAL EVALUATION | en |
dc.subject | ANTIVIRAL | en |
dc.subject | ACTIVITY | en |
dc.subject | 1,5-ANHYDROHEXITOL NUCLEOTIDES | en |
dc.subject | UNSATURATED EXOMETHYLENE | en |
dc.subject | EFFICIENT SYNTHESIS | en |
dc.subject | DRUG-RESISTANCE | en |
dc.subject | DERIVATIVES | en |
dc.subject | AGENTS | en |
dc.subject | KETONUCLEOSIDES | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.subject | Chemistry, Organic | en |
dc.title | Synthesis of 4,6-dideoxy-3-fluoro-2-keto-beta-D-glucopyranosyl analogues of 5-fluorouracil, N-6-benzoyl adenine, uracil, thymine, N-4-benzoyl cytosine and evaluation of their antitumor activities | en |
dc.type | journalArticle | en |