title: Stereocontrolled synthesis of 4'-C-cyano and 4'-C-cyano-4'-deoxy pyrimidine pyranonucleosides as potential chemotherapeutic agents.
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.
authors.affiliation: Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Kiritsis
authors.forename: Stella
authors.initials: S
authors.lastname: Manta
authors.forename: Vanessa
authors.initials: V
authors.lastname: Parmenopoulou
authors.forename: Athina
authors.initials: A
authors.lastname: Dimopoulou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kollatos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papasotiriou
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Dimitri
authors.initials: D
authors.lastname: Komiotis
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008358:Mannose / Q000031:analogs & derivatives / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012966:Sodium Cyanide / Q000737:chemistry; D013237:Stereoisomerism; D013941:Thymine / Q000737:chemistry; D014498:Uracil / Q000737:chemistry
chemical_list: C580639:1-(4'-C-cyano-4'-C-deoxy)-5-fluorouracil; C580638:1-(4'-C-cyanomannopyranosyl)-5-fluorouracil; D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D009570:Nitriles; D011741:Pyrimidine Nucleosides; C430593:cyanohydrin; D014498:Uracil; D012966:Sodium Cyanide; D008358:Mannose; D013941:Thymine; D010100:Oxygen; D005472:Fluorouracil