Efficient synthesis of exomethylene- and keto-exomethylene-D-glucopyranosyl nucleoside analogs as potential cytotoxic agents
dc.creator | Tzioumaki, N. | en |
dc.creator | Tsoukala, E. | en |
dc.creator | Manta, S. | en |
dc.creator | Kiritsis, C. | en |
dc.creator | Balzarini, J. | en |
dc.creator | Komiotis, D. | en |
dc.date.accessioned | 2015-11-23T10:52:45Z | |
dc.date.available | 2015-11-23T10:52:45Z | |
dc.date.issued | 2011 | |
dc.identifier | 10.1016/j.carres.2010.10.019 | |
dc.identifier.issn | 0008-6215 | |
dc.identifier.uri | http://hdl.handle.net/11615/34127 | |
dc.description.abstract | A novel series of exomethylene- and keto-exomethylene-D-glucopyranonucleosides with thymine, uracil, and 5-fluorouracil as heterocyclic bases have been designed and synthesized. Wittig condensation of the 3-keto glucoside 1 gave the corresponding 1,2:5,6-di-O-isopropylidene-3-deoxy-3-methylene-D-glucofuranose (2), which after hydrolysis and acetylation led to the precursor 1,2,4,6-tetra-O-acetyl-3-deoxy-3-methylene-D-glucopyranose (4).Compound 4 was condensed with silylated thymine, uracil, and 5-fluorouracil, respectively, deacetylated and acetalated to afford 1-(3'-deoxy-4',6'-O-isopropylidene-3'-methylene-beta-D-glucopyranosyl)pyrimidines 7a-c. Oxidation of the free hydroxyl group in the 2'-position of the sugar moiety led to the formation of the labile 1-(3'-deoxy-4',6'-O-isopropylidene-3'-methylene-beta-D-glucopyranosyl-2'-ulose)pyrimidines 8a-c. Finally, deisopropylidenation of the resulted derivatives 8a-c afforded the diol nucleosides 9a-c. The target keto-exomethylene analogs 9a-c were more cytostatic against a variety of tumor cell lines than the corresponding saturated-hydroxy-exomethylene derivatives 6. In particular, the 5-fluorouracil derivative 9c was highly cytostatic at an IC(50)(50% inhibitory concentration) ranging between 0.56 and 9.4 mu g/mL, which was comparable to the free parental 5-fluorouracil base. (C) 2010 Elsevier Ltd. All rights reserved. | en |
dc.source | Carbohydrate Research | en |
dc.source.uri | <Go to ISI>://WOS:000287111400023 | |
dc.subject | Unsaturated nucleosides | en |
dc.subject | Exomethylene nucleosides | en |
dc.subject | Ketonucleosides | en |
dc.subject | Cytotoxicity | en |
dc.subject | 5-Fluorouracil | en |
dc.subject | FLUORO-KETOPYRANOSYL NUCLEOSIDES | en |
dc.subject | BIOLOGICAL EVALUATION | en |
dc.subject | N-4-BENZOYL | en |
dc.subject | CYTOSINE | en |
dc.subject | N-6-BENZOYL ADENINE | en |
dc.subject | SECONDARY ALCOHOLS | en |
dc.subject | ANTIVIRAL AGENTS | en |
dc.subject | 1,5-ANHYDROHEXITOL NUCLEOTIDES | en |
dc.subject | UNSATURATED EXOMETHYLENE | en |
dc.subject | CONFORMATIONAL-ANALYSIS | en |
dc.subject | DRUG-RESISTANCE | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.subject | Chemistry, Applied | en |
dc.subject | Chemistry, Organic | en |
dc.title | Efficient synthesis of exomethylene- and keto-exomethylene-D-glucopyranosyl nucleoside analogs as potential cytotoxic agents | en |
dc.type | journalArticle | en |
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