Synthesis of 2-amino-6-(4-[11C]methoxyphenylthio)9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester as a novel potential PET gene reporter probe for HBV and HSV-tk in cancers

Acyclic nucleoside 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (ABE, 1) is a new hepatitis B virus (HBV) specific antiviral reagent and shows high anti-HBV activity. Carbon-11 labeled ABE may serve as a novel reporter probe for positron emission tomography (PET) to image HBV and herpes simplex virus thymidine kinase (HSV-tk) in cancers. The radiolabeling precursors 2-amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (10) and 2-N-Boc protected analogue 2-N-bis(Boc)amino-6-(4-hydroxyphenylthio)9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (12), and the reference standard ABE were synthesized from bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate (5), guanine (6), and 2-amino-6-chloropurine (8). The target radiotracer 2-amino-6-(4-[C-11]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([C-11]ABE, [C-11]1) was prepared by O-[C-11]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [C-11]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields. (C) 2004 Elsevier Ltd. All rights reserved.