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

(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-iodouracil (3) to give 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)ethynyl]uracil (4). Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-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-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 [I-125]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 [I-125]IVAraU may allow automated in vitro detection of HSV isolates.