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
- Department of Chemistry, Brigham Young University, Provo, UT (USA)
(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{asterisk}I gave ({asterisk}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.
- OSTI ID:
- 5451160
- Journal Information:
- Journal of Medicinal Chemistry; (United States), Vol. 34:7; ISSN 0022-2623
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HERPES SIMPLEX
BIOLOGICAL MARKERS
URACILS
STRUCTURE-ACTIVITY RELATIONSHIPS
CHEMICAL PREPARATION
IODINE 125
PHOSPHOTRANSFERASES
RABBITS
TRACER TECHNIQUES
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PYRIMIDINES
RADIOISOTOPES
SKIN DISEASES
SYNTHESIS
TRANSFERASES
VERTEBRATES
VIRAL DISEASES
550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques