Efficient syntheses of [11C]zidovudine and its analogs by convenient one‐pot palladium(0)–copper(I) co‐mediated rapid C‐[11C]methylation |
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| Authors: | Zhouen Zhang Hisashi Doi Hiroko Koyama Yasuyoshi Watanabe Masaaki Suzuki |
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| Affiliation: | 1. Division of Bio‐function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), Kobe, Hyogo, Japan;2. RIKEN Center for Molecular Imaging Science, Kobe, Hyogo, Japan;3. Division of Regeneration and Advanced Medical Science, Graduated School of Medicine, Gifu University, Gifu, Japan;4. Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu‐shi, Aichi, Japan |
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| Abstract: | The nucleosides zidovudine (AZT), stavudine (d4T), and telbivudine (LdT) are approved for use in the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. To promote positron emission tomography (PET) imaging studies on their pharmacokinetics, pharmacodynamics, and applications in cancer diagnosis, a convenient one‐pot method for Pd(0)–Cu(I) co‐mediated rapid C–C coupling of [11C]methyl iodide with stannyl precursor was successfully established and applied to synthesize the PET tracers [11C]zidovudine, [11C]stavudine, and [11C]telbivudine. After HPLC purification and radiopharmaceutical formulation, the desired PET tracers were obtained with high radioactivity (6.4–7.0 GBq) and specific radioactivity (74–147 GBq/µmol) and with high chemical (>99%) and radiochemical (>99.5%) purities. This one‐pot Pd(0)–Cu(I) co‐mediated rapid C‐[11C]methylation also worked well for syntheses of [methyl‐11C]thymidine and [methyl‐11C]4′‐thiothymidine, resulting twice the radioactivity of those prepared by a previous two‐pot method. The mechanism of one‐pot Pd(0)–Cu(I) co‐mediated rapid C‐[11C]methylation was also discussed. |
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| Keywords: | [11C]Zidovudine ([11C]AZT) [11C]Telbivudine ([11C]LdT) [11C]Stavudine ([11C]d4T) [Methyl‐11C]thymidine [Methyl‐11C]4′ ‐thiothymidine ([11C]4DST) Rapid C‐[11C]methylation |
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