title: Nucleic acid related compounds. 65. New syntheses of 1-(beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from vinylsilane precursors. Radioiodine uptake as a marker for thymidine kinase positive herpes viral infections.
abstract: (Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D- arabinofuranosyl)-5-iodouracil to give 1- (2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)eth yny l] uracil. Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. Treatment of 5 with iodine monochloride (or sodium iodide/phenyliodine(III) dichloride) in benzene gave 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (7), whereas polar solvents favored the (Z)-iodovinyl isomer 8. Deacetylation of 7 gave 1-(beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU, 9). A microscale in situ synthesis with Na*I gave [*I]IVAraU. Treatment of HSV-infected cells with [125I]IVAraU resulted in virus-dependent uptake associated with nucleoside phosphorylation by wild type or acyclovir-resistant DNA polymerase mutants (but not with TK-HSV-1 mutants). Uptake was virus-inoculum dependent and was detectable within 4 h postinfection. The process was not completely reversible. Virus-specified uptake of [125I]IVAraU may allow automated in vitro detection of HSV isolates.
authors.affiliation: Department of Chemistry, Brigham Young University, Provo, Utah 84602.
authors.forename: M J
authors.initials: MJ
authors.lastname: Robins
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.forename: S G
authors.initials: SG
authors.lastname: Wood
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanklin
authors.forename: B A
authors.initials: BA
authors.lastname: Rennie
authors.forename: S L
authors.initials: SL
authors.lastname: Sacks
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002621:Chemistry; D006561:Herpes Simplex / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D011817:Rabbits; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D007457:Iodine Radioisotopes; D001086:Arabinofuranosyluracil; C052250:arabinofuranosyl-E-5-iodovinyluracil; D013937:Thymidine Kinase