title: Branched-chain sugar nucleosides: stereocontrolled synthesis and bioevaluation of novel 3'-C-trifluoromethyl and 3'-C-methyl pyranonucleosides.
abstract: A new series of 3'-C-trifluoromethyl- and 3'-C-methyl-β-d-allopyranonucleosides of 5-fluorouracil and their deoxy derivatives has been designed and synthesized. Treatment of ketosugar 1 with trifluoromethyltrimethylsilane under catalytic fluoride activation and methyl magnesium bromide, gave 1,2:5,6-di-O-isopropylidene-3-C-trifluoromethyl (2a) and 3-C-methyl (2b)-α-D-allofuranose, respectively, in a virtually quantitative yield and with complete stereoselectivity. Hydrolysis followed by acetylation led to the 1,2,4,6-tetra-O-acetyl-3-C-trifluoromethyl (3a) and 3-C-methyl (3b)-β-D-allopyranose. Compounds 3a,b were then condensed with silylated 5-fluorouracil and deacetylated to afford the target nucleosides 5a,b. Deoxygenation of the peracylated allopyranoses 3a,b followed by condensation with silylated 5-fluorouracil and subsequent deacetylation yielded the target 3'-deoxy-3'-C-trifluoromethyl and 3'-deoxy-3'-C-methyl-β-d-glucopyranonucleosides 14a,b. The newly synthesized compounds were evaluated for their potential antiviral and cytostatic activities. The 3'-deoxy-3'-C-methyl- ribonucleoside 11b showed significant cytotoxic activity (∼7 μM) almost equally active against a variety of tumor cell lines.
authors: Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece.
authors: Nikolaos
authors: N
authors: Kollatos
authors: Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece.
authors: Stella
authors: S
authors: Manta
authors: Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece.
authors: Athina
authors: A
authors: Dimopoulou
authors: Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece.
authors: Vanessa
authors: V
authors: Parmenopoulou
authors: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors: Virginia V
authors: VV
authors: Triantakonstanti
authors: Department of Chemistry, Laboratory of Organic Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, Zografou 15771, Greece; Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, GR-45110 Ioannina, Greece.
authors: Tahsin
authors: T
authors: Kellici
authors: Department of Chemistry, Laboratory of Organic Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, Zografou 15771, Greece.
authors: Thomas
authors: T
authors: Mavromoustakos
authors: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors: Dominique
authors: D
authors: Schols
authors: Department of Biochemistry and Biotechnology, Laboratory of Bioorganic Chemistry, University of Thessaly, 41221 Larissa, Greece. Electronic address: dkom@bio.uth.gr.
authors: Dimitri
authors: D
authors: Komiotis
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002236:Carbohydrate Conformation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D025942:Oligosaccharides, Branched-Chain / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D054697:Cytostatic Agents; D009705:Nucleosides; D025942:Oligosaccharides, Branched-Chain
keywords: 5-Fluorouracil; C-Methyl nucleosides; C-Trifluoromethyl nucleosides; Cytotoxicity