ABSTRACT
Methyl 3,5-anhydro-alpha-D-xylofuranosides are obtained by use of the Mitsunobu reaction from 2-O-protected methyl alpha-D-xylofuranosides, which are easily prepared from D-xylose. The Mitsunobu reaction of methyl 3-N-benzylamino-3-deoxy- and 3-azido-3-deoxyarabinofuranosides, which are prepared from the conveniently available methyl 2,3-anhydro-alpha-D- and 2,3-anhydro-alpha-l-lyxofuranosides by nucleophilic ring opening, yields the corresponding methyl 2,5-anhydro-alpha-D- and 2,5-anhydro-alpha-l-arabinofuranosides. Ring opening of 3,5-anhydro-1,2-O-isopropylidene-alpha-D-xylofuranose with azide yields the corresponding 5-azido derivative. The structure and configuration of the products is confirmed by NMR spectroscopy. 5,6-Anhydro-1,2-O-isopropylidene-alpha-D-glucofuranose is formed by the Mitsunobu reaction of 1,2-O-isopropylidene-alpha-D-glucofuranose. Its structure is verified by single-crystal X-ray diffraction analysis.
Subject(s)
Arabinose/analogs & derivatives , Arabinose/chemistry , Furans/chemistry , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Optical Rotation , Pyridines/chemistry , Xylose/chemistryABSTRACT
Methyl 2,5-anhydro-3-O-(2-methoxyethyl)-2-thio-beta-D-arabinofuranoside and methyl 2,5-anhydro-3-O-(2-fluorobenzyl)-2-thio-alpha-D-lyxofuranoside were transformed into the corresponding uridine, thymidine, cytidine and adenosine analogues, which exclusively exhibited the alpha-configuration irrespective of the anomeric configuration of the donor. The structure, configuration, and conformation of the products was elucidated by X-ray structure analyses. The nucleoside analogues were tested for antiviral activities.
Subject(s)
Carbohydrates/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Carbohydrates/chemistry , Carbohydrates/pharmacology , Cell Line , Crystallography, X-Ray , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Models, Molecular , Spectrometry, Mass, Fast Atom Bombardment , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacologyABSTRACT
The unprotected methyl L-arabinofuranosides, D-ribofuranosides and D-xylofuranosides are transformed into the corresponding S-acetyl-5-thio derivatives by the thio-Mitsunobu reaction. Mesylation and subsequent reaction with sodium hydrogen carbonate led, depending on the configuration of the intermediate, to 2,5-anhydro-2-thio- or 3,5-anhydro-3-thiopentofuranosides. Due to inversion at C-3 or C-2 during the intramolecular nucleophilic displacement the products exhibit L-lyxo-, D-arabino- or D-lyxo-configuration. Analogously, the methyl 2,3-anhydro-D-ribofuranosides yielded 5-thio-S-acetates with intact 2,3-oxirane groups, which were cyclised with sodium hydrogen carbonate by epoxide ring opening and concomitant ring closure to form exclusively 3,5-anhydro-3-thio-D-xylofuranosides. A related 3,5-anhydro-3-seleno-D-lyxofuranoside was obtained by reaction of a 3,5-di-O-mesyl-D-arabinofuranoside with sodium hydrogen selenide. Several X-ray diffraction analyses proved the structures of the products.
Subject(s)
Arabinose/chemistry , Acetates/chemistry , Bicarbonates/chemistry , Biochemical Phenomena , Biochemistry , Crystallography, X-Ray , Furans/chemistry , Hydrogen/chemistry , Magnetic Resonance Spectroscopy , Models, Chemical , Models, Molecular , Selenic Acid , Selenium Compounds/chemistry , Sodium/chemistry , X-Ray Diffraction , Xylose/chemistryABSTRACT
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose 1 was transformed into O-benzyl- and O-acetyl-protected 1-(4-thio-L-lyxofuranosyl) nucleoside derivatives by use of the TMSOTf method. Debenzylation with boron tribromide or deacetylation with sodium methoxide yielded the corresponding pyrimidine (7-11, 17, 18, 26 and 27) and purine (29 and 34) nucleoside analogues. The anomeric configurations were determined by NMR spectroscopy and, in the case of the 5-halo- (7-9) and nitrouridine derivative 11 and the 6-methylcytidine derivative 27, by X-ray structural analyses.--The unprotected nucleosides were not anti-virically inhibitory at 250 microM.
Subject(s)
Nucleosides/chemistry , Pentoses/chemistry , Thiophenes/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Structure , Nucleic Acid Denaturation , Nucleosides/pharmacology , Protons , X-Ray DiffractionABSTRACT
New isonucleosides [methyl 5-(1-pyrimidinyl)furanosides] are prepared by nucleophilic opening of the oxetane ring of methyl 3,5-anhydro-2-O-(2-fluorobenzyl)-D-xylofuranoside with silylated pyrimidine bases in the presence of trimethylsilyl triflate. Structures, configurations and conformations were determined by NMR techniques and several X-ray diffraction analyses, seven of the isonucleosides were tested for cytotoxicity and activity against HIV, HSV and several other viruses.
