Abstract
A new series of 4'-C-cyano and 4'-C-cyano-4'-deoxy pyrimidine pyranonucleosides has been designed and synthesized. Commercially available 1,2,3,4,6-penta-O-acetyl-D-mannopyranose (1) was condensed with silylated 5-fluorouracil, uracil, and thymine, respectively to afford after deacetylation 1-(α-D-mannopyranosyl)nucleosides (2a-c). Subjecting 2a-c to the sequence of specific acetalation, selective protection of the primary hydroxyl group and oxidation, the 4'-ketonucleosides 6a-c and 7c were obtained. Reaction of compounds 6a,b, and 7c with sodium cyanide and subsequent deprotection gave the target 1-(4'-C-cyano-α-D-mannopyranosyl)nucleosides 12a-c. Deoxygenation at the 4'-position of cyanohydrins 8a,b, and 11c followed by deprotection led to the desired 1-(4'-C-cyano-4'-deoxy-α-D-talopyranosyl)nucleosides (15a-c). The newly synthesized compounds were evaluated for their potential antiviral and cytostatic activities in cell culture.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cytostatic Agents / chemical synthesis
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Cytostatic Agents / chemistry
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Cytostatic Agents / pharmacology
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Drug Design
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Fluorouracil / analogs & derivatives*
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Fluorouracil / chemical synthesis*
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Fluorouracil / chemistry
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Fluorouracil / pharmacology
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HeLa Cells
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Humans
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Inhibitory Concentration 50
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Mannose / analogs & derivatives
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Mannose / chemistry
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Nitriles / chemistry
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Oxidation-Reduction
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Oxygen / chemistry
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Pyrimidine Nucleosides / chemical synthesis*
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Pyrimidine Nucleosides / chemistry
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Pyrimidine Nucleosides / pharmacology
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Sodium Cyanide / chemistry
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Stereoisomerism
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Thymine / chemistry
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Uracil / chemistry
Substances
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1-(4'-C-cyano-4'-C-deoxy)-5-fluorouracil
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1-(4'-C-cyanomannopyranosyl)-5-fluorouracil
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Antineoplastic Agents
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Cytostatic Agents
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Nitriles
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Pyrimidine Nucleosides
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cyanohydrin
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Uracil
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Sodium Cyanide
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Mannose
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Thymine
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Oxygen
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Fluorouracil