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Synthesis of [ 18 F]norchlorofluoroepibatidine and its N‐methyl derivative: new PET ligands for mapping nicotinic acetylcholine receptors
Author(s) -
Ding Y.S.,
Liang F.,
Fowler J. S.,
Kuhar M. J.,
Carroll F. I.
Publication year - 1997
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199710)39:10<827::aid-jlcr29>3.0.co;2-7
Subject(s) - chemistry , methyl iodide , fluoride , nucleophilic substitution , propionitrile , nicotinic agonist , medicinal chemistry , ligand (biochemistry) , sodium methoxide , heptane , radiosynthesis , trifluoroacetic acid , stereochemistry , receptor , organic chemistry , methanol , acetonitrile , inorganic chemistry , biochemistry , microbiology and biotechnology , in vivo , biology
Fluorine‐18 labeled norchlorofluoroepibatidine (NFEP), a high‐affinity nicotinic acetylcholine receptor ligand, was prepared by a one‐pot, two‐step synthesis: nucleophilic heteroaromatic substitution of a tert ‐Boc protected precursor (7‐ tert ‐butyloxycarbonyl‐exo‐2‐(2′‐N,N,N‐trimethylammonium‐5′‐pyridinyl)‐7‐azabicyclo[2.2.1]heptane iodide) using no‐carrier‐added [ 18 F]fluoride followed by deprotection with trifluoroacetic acid. Subsequent reductive N‐methylation with formaldehyde and sodium cyanoborohydride afforded fluorine‐18 labeled N‐methyl‐norchlorofluoroepibatidine (N‐methyl‐NFEP). The unusually high radiochemical yield for the first step (70%) and the quantitative conversions in the deprotection and N‐methylation steps afforded overall radiochemical yields of 55–65% (decay corrected based on starting [ 18 F]fluoride) for [ 18 F]NFEP (synthesis time 65 min) and 45–55% for [ 18 F]N‐methyl‐NFEP (synthesis time 75 min), with a specific activity of 2–9 Ci/μmole (EOB). © 1997 John Wiley & Sons, Ltd.