Nucleic Acid Related Compounds. 65. New Syntheses of 1-(β-D-Arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from Vinylsilane Precursors. Radioiodine Uptake as a Marker for Thymidine Kinase Positive Herpes Viral Infections

Article abstract of DOI:10.1021/jm00111a050

(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-iodouracil (3) to give 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil (4).Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-β-D-arabinofuranosyl)-5(Z)-<2-(trimethylsilyl)vinyl>uracil (5).Treatment of 5 with iodine monochloride (or sodium iodide/phenyliodine(III) dichloride) in benzene gave 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (7), whereas polar solvents favored the (Z)-iodovinyl isomer 8.Deacetylation of 7gave 1-β-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.