Synthesis of the stable isotope labeled antiviral nucleoside analog [8-13C-7,9-15N2]-ganciclovir

Naiyu Zheng, Santosh Tilve, Tomoyuki Oe, Steven M. Albelda, Suzanne Wehrli, Ian A. Blair

Research output: Contribution to journalArticlepeer-review

Abstract

Ganciclovir, a nucleoside analog of 2′-deoxyguanosine, is a drug used in suicide gene therapy for the treatment of mesothelioma. We required a stable isotope analog of ganciclovir for use in pharmacokinetic studies in order to monitor the systemic exposure of patients to the drug. Therefore, a facile and efficient synthesis of [8-13C-7,9-15N2]- ganciclovir, was devised. The synthesis was achieved in 4 steps with 25% total yield using commercially-available [8-13C-7,9-15N 2]-guanine, without the need for purification of intermediates. The key step of the synthesis involved the coupling of [8-13C-7,9- 15N2]-guanine with 3-propionyloxy-2-propionyloxy- methoxypropyl propionate. The latter was synthesized from a commercially available dichlorohydrin. Each step of the reaction could be easily monitored by liquid chromatography-mass spectrometry. The structure of the labeled ganciclovir was confirmed using 1H, 13C, and 15N nuclear magnetic resonance spectroscopy.

Original languageEnglish
Pages (from-to)1131-1139
Number of pages9
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume49
Issue number13
DOIs
Publication statusPublished - 2006 Nov 1
Externally publishedYes

Keywords

  • Ganciclovir
  • Liquid chromatography/mass spectrometry
  • Nuclear magnetic resonance spectroscopy
  • Nucleoside
  • Stable isotopes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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