No-carrier-added [123I]1-(β-d-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVaraU): High yielding radiolabeling via organotin and exchange reactions

Dougan, H.; Rennie, Bruce A.; Lyster, Donald M.; Sacks, Stephen L.

doi:10.1016/0969-8043(94)90131-7

Cited by 16 publications

(9 citation statements)

References 27 publications

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“…Similarly, carrier-added and high specific activity products have been isolated in respectable radiochemical yields using modified Hunsdiecker reactions . Recent reports for the highly efficient radiosyntheses of labeled IVAU from vinylstannane and vinylsilane precursors under mild conditions are particularly appealing. , However, radioiodination of these precursors has only been attempted using protected nucleosides. Deprotection after radiohalogenation requires additional undesired laboratory handling of radioactive materials, which results in some loss of radiolabeled product.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

et al. 1997

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A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5-(2-[125I]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)-5-(2-[125I]Iodovinyl)-2'-deoxyuridine ([125I]IVDU, 10), (E)-5-(2-[125I]iodovinyl)-2'-fluoro-2'-deoxyuridine ([125I]IVFRU, 11), (E)-5-(2-[125I]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([125I]IVFAU, 12), and (E)-5-(2-[125I]iodovinyl)arabinouridine ([125I]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)-5-(2-(trimethylsilyl)vinyl) precursors (6-9) with [125I]ICl. Cellular uptake of these labeled compounds (10-13) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.

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Section: Chemistrymentioning

confidence: 99%

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

et al. 1997

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“…6–9 However, the tendency of ( E )-5-[2-(tributylstannyl)vinyl]arabinosyl uridine 8 and 5-trimethylstannyl araU 9 to protiodestannylation was noted.…”

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confidence: 99%

Hydrogermylation of 5-Ethynyluracil Nucleosides: Formation of 5-(2-Germylvinyl)uracil and 5-(2-Germylacetyl)uracil Nucleosides

2013

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A stereoselective radical-mediated hydrogermylation of the protected 5-ethynyluracil nucleosides with trialkyl-, triaryl,- or tris(trimethylsilyl)-germanes gave (Z)-5-(2-germylvinyl)-uridine, 2'-deoxyuridine or ara-uridine as major products. Reaction of the β-triphenylgermyl vinyl radical intermediate with oxygen and fragmentation of the resulting peroxyradical provided also 5-[2-(triphenylgermyl)acetyl] pyrimidine nucleosides in low to moderate yields. Thermal isomerization of the latter in MeOH occurred via a four-centered activated complex and subsequent hydrolysis of the resulting O-germyl substituted enol yielded 5-acetyluracil nucleosides in quantitative yield.

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“…8 Though the syntheses of [ 123 I] IVAU and its precursor TSVAU {(E)-5-[2-(tributylstannyl)-vinyl]arabinosyl uridine} 2 have been reported by Dougan et al, the use of acetylene during production of trans-1,2-distannyl ethene was a formidable procedure for the most medicinal chemistry laboratories. 9 Consequently, an alternative precursor bearing trimethylsilyl vinyl group was developed by Morin et al and [ 125 I]IVAU 1 could be prepared in fair yield.…”

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confidence: 99%

Synthesis of (E)-5-(2-Radioiodovinyl)arabinosyl Uridine Analog for Probing HSV-1 Thymidine Kinase Gene

Chiang

et al. 2005

Chemistry Letters

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The genetic probe labeled with positron emitter for monitoring tumor cells transfacted by herpes simplex virus thymidine kinase gene has been intensively studied. A useful synthetic methodology was developed to synthesize (E)-5- [2-(tributylstannyl) Gene therapy has become one of the most promising approaches for cancer treatment. The mechanism underlying the therapy starts by delivering the suicide gene into the target cells, followed by administering the prodrugs. The presence of the suicide gene in the target cells activates the prodrugs, such as nucleoside analogs, to form toxic metabolites, which then initiate the subsequent suicidal mechanism. The most intensively studied suicide gene, HSV-1 TK (herpes simplex virus thymidine kinase), can serve bi-functionally as both therapeutic and reporter genes in this system.2 Moreover, in vivo gene expression of HSV-1 TK can be successfully monitored by imaging its substrate analog, usually a nucleoside analog. After being phosphorylated by viral TK, the metabolite can be randomly incorporated into elongating DNA chains by cellular enzymes.3 The localization of this event could be traced down by using a tagged nucleoside analog. Of the most excellent candidates for in vivo studies are which radiolabeled with positron emitters owing to their higher imaging quality and quantification capacity. For example, [124 I]FIAU (pyrimidine nucleoside) and [ 18 F]FHBG (purine nucleoside) have been coupled with PET (positron emission tomography) to provide invaluable images (Scheme 1). 4,5 Recently, an investigation on bioactivity-guided screening of nucleosides as substrates for HSV-1 TK by Degrève et al. discovered two potential compounds: IaraU (5-iodoarabinosyl uridine) and IVAU {(E)-5-(2-iodovinyl)arabinosyl uridine} 1 (Scheme 2). 6 As part of our systematic syntheses of radiolabeled thymidine analogs, 7

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No-carrier-added [123I]1-(β-d-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVaraU): High yielding radiolabeling via organotin and exchange reactions

Cited by 16 publications

References 27 publications

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

Hydrogermylation of 5-Ethynyluracil Nucleosides: Formation of 5-(2-Germylvinyl)uracil and 5-(2-Germylacetyl)uracil Nucleosides

Synthesis of (E)-5-(2-Radioiodovinyl)arabinosyl Uridine Analog for Probing HSV-1 Thymidine Kinase Gene

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No-carrier-added [123I]1-(β-d-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVaraU): High yielding radiolabeling via organotin and exchange reactions

Cited by 16 publications

References 27 publications

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[125I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[125I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

Hydrogermylation of 5-Ethynyluracil Nucleosides: Formation of 5-(2-Germylvinyl)uracil and 5-(2-Germylacetyl)uracil Nucleosides

Synthesis of (E)-5-(2-Radioiodovinyl)arabinosyl Uridine Analog for Probing HSV-1 Thymidine Kinase Gene

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Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy