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

Ji Quan Wang, Xiangshu Fei, Thomas Gardner, Gary Hutchins, Qi-Huang Zheng

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Abstract

Synthesis of radiolabeled antiviral nucleoside analogue 2-amino-6-(4-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE) as a novel potential PET reporter probe for hepatitis B virus (HBV) and herpes simplex virus thymidine kinase (HSV-tk) in cancers is reported. 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-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE, [ 11C]1) was prepared by O-[ 11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [ 11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields.

Original languageEnglish
Pages (from-to)549-556
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number2
DOIs
StatePublished - Jan 17 2005

Fingerprint

Positron emission tomography
Thymidine Kinase
Simplexvirus
Reporter Genes
Viruses
Hepatitis B virus
Positron-Emission Tomography
Esters
Genes
Nucleosides
Antiviral Agents
Neoplasms
Solid Phase Extraction
Guanine
Methylation
Carbon
Purification
2-amino-6-(4-methoxyphenylthio)-9-(2-(phosphonomethoxy)ethyl)purine bis(2,2,2-trifluoroethyl) ester
purine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

@article{26c276eedfdd40a3ad993bb8befa4ff3,
title = "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",
abstract = "Synthesis of radiolabeled antiviral nucleoside analogue 2-amino-6-(4-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE) as a novel potential PET reporter probe for hepatitis B virus (HBV) and herpes simplex virus thymidine kinase (HSV-tk) in cancers is reported. 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-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE, [ 11C]1) was prepared by O-[ 11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [ 11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55{\%} radiochemical yields.",
author = "Wang, {Ji Quan} and Xiangshu Fei and Thomas Gardner and Gary Hutchins and Qi-Huang Zheng",
year = "2005",
month = "1",
day = "17",
doi = "10.1016/j.bmc.2004.10.007",
language = "English",
volume = "13",
pages = "549--556",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
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TY - JOUR

T1 - 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

AU - Wang, Ji Quan

AU - Fei, Xiangshu

AU - Gardner, Thomas

AU - Hutchins, Gary

AU - Zheng, Qi-Huang

PY - 2005/1/17

Y1 - 2005/1/17

N2 - Synthesis of radiolabeled antiviral nucleoside analogue 2-amino-6-(4-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE) as a novel potential PET reporter probe for hepatitis B virus (HBV) and herpes simplex virus thymidine kinase (HSV-tk) in cancers is reported. 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-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE, [ 11C]1) was prepared by O-[ 11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [ 11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields.

AB - Synthesis of radiolabeled antiviral nucleoside analogue 2-amino-6-(4-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE) as a novel potential PET reporter probe for hepatitis B virus (HBV) and herpes simplex virus thymidine kinase (HSV-tk) in cancers is reported. 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-[ 11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) ester ([ 11C]ABE, [ 11C]1) was prepared by O-[ 11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [ 11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields.

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