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: Zhouen Zhang, Hisashi Doi, Hiroko Koyama, Yasuyoshi Watanabe, Masaaki Suzuki
• Journal: Journal of labelled compounds & radiopharmaceuticals (J Labelled Comp Radiopharm) Vol. 57 Issue 8 Pg. 540-9 (Jun 30 2014) ISSN: 1099-1344 [Electronic] England
• PMID: 24992010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 John Wiley & Sons, Ltd.

Chemical References

• Carbon Radioisotopes
• Radiopharmaceuticals
• Zidovudine
• Palladium
• Copper

Topics

• Carbon Radioisotopes (chemistry)
• Catalysis
• Chemistry Techniques, Synthetic (methods)
• Copper (chemistry)
• Methylation
• Palladium (chemistry)
• Radiopharmaceuticals (chemical synthesis)
• Zidovudine (analogs & derivatives, chemical synthesis)