title: [Synthesis, conversion and biological activity of 5-substituted 2'-deoxyuridines modified by carbohydrates].
abstract: 5-Benzyloxymethyl(Bom)-2'-deoxyuridine and its alpha-anomer were used as the key compounds for syntheses of thymidine analogues or 3'-derivatives. Anomeric 5-Bom-2'-deoxyuridines were synthesized from 5-Bom-uracil and 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribo-furanosyl chloride by means of the silyl method. 5-Bom-2'-deoxyuridine was transformed successively to 3',5'-di-O-mesyl derivative, 2,3'-anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofuranosyl)-5-Bom-uracil and 3'-azido-2',3'-dideoxy-5-Bom-uridine. Treatment of the last with SnCl4 in methylene dichloride--methanol led to 3'-azido-2',3'-dideoxy-5-methoxymethyluridine. Under the same conditions the 5-methoxymethyl derivative was obtained from 3',5'-di-O-p-toluyl-5-Bom-2'-deoxyuridine. Interaction of 1-(2-deoxy-alpha-D-ribofuranosyl)-4-Bom-uracil with SnCl4 in methylene dichloride as well as the hydrogen transfer hydrogenolysis in the presence of cyclohexene and Pd(OH)2/C in ethanol led to 1-(2-deoxy-alpha-D-ribofuranosyl)-5-hydroxymethyluracil. Only 3'-azido-2',3'-dideoxy-5-Bom-uridine showed a cytotoxic activity against CaOv cells in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA by 78.8-95.1%. Elucidation of antitumor activity in vivo showed that this nucleoside inhibits growth of solid tumours, Ca755 and LLC, by 79 and 79-83%, respectively, but has no therapeutic effect against lympholeukemia P388.
authors.forename: S Ia
authors.initials: SIa
authors.lastname: Mel'nik
authors.forename: A A
authors.initials: AA
authors.lastname: Bakhmedova
authors.forename: I V
authors.initials: IV
authors.lastname: Iartseva
authors.forename: O S
authors.initials: OS
authors.lastname: Zhukova
authors.forename: N P
authors.initials: NP
authors.lastname: Iavorskaia
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D003857:Deoxyuridine / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy
chemical_list: D002241:Carbohydrates; D003857:Deoxyuridine
vernacular_title: Sintez, prevrashcheniia i biologicheskaia aktivnost' modifitsirovannykh po uglevodu 5-zameshchennykh 2'-dezoksiuridinov.