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.
|Number of pages||9|
|Journal||Journal of Labelled Compounds and Radiopharmaceuticals|
|Publication status||Published - 2006 Nov|
- Liquid chromatography/mass spectrometry
- Nuclear magnetic resonance spectroscopy
- Stable isotopes