title: Efficient syntheses of [¹¹C]zidovudine and its analogs by convenient one-pot palladium(0)-copper(I) co-mediated rapid C-[¹¹C]methylation.
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 [(11)C]methyl iodide with stannyl precursor was successfully established and applied to synthesize the PET tracers [(11)C]zidovudine, [(11)C]stavudine, and [(11)C]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-[(11)C]methylation also worked well for syntheses of [methyl-(11)C]thymidine and [methyl-(11)C]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-[(11)C]methylation was also discussed.
authors.affiliation: Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), Kobe, Hyogo, 650-0047, Japan; RIKEN Center for Molecular Imaging Science, Kobe, Hyogo, 650-0047, Japan.
authors.forename: Zhouen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Koyama
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D003300:Copper / Q000737:chemistry; D008745:Methylation; D010165:Palladium / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D015215:Zidovudine / Q000031:analogs & derivatives / Q000138:chemical synthesis*
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D015215:Zidovudine; D010165:Palladium; D003300:Copper
keywords: Rapid C-[11C]methylation; [11C]Stavudine ([11C]d4T); [11C]Telbivudine ([11C]LdT); [11C]Zidovudine ([11C]AZT); [Methyl-11C]4′-thiothymidine ([11C]4DST); [Methyl-11C]thymidine