Naiyu Zheng, S. Tilve, T. Oe
Nov 1, 2006
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Journal
Journal of Labelled Compounds and Radiopharmaceuticals
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–7,9-15N2]-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. Copyright © 2006 John Wiley & Sons, Ltd.