Molecular Imaging Branch National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1003, USA.
Gordon Center for Medical Imaging Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA <02114-1107>, postcode missing<02114-1107>, USA.
Chemistry. 2023 Apr 25;29(24):e202204004. doi: 10.1002/chem.202204004. Epub 2023 Mar 20.
Efficient methods for labeling aryl trifluoromethyl groups to provide novel radiotracers for use in biomedical research with positron emission tomography (PET) are keenly sought. We report a broad-scope method for labeling trifluoromethylarenes with either carbon-11 (t =20.4 min) or fluorine-18 (t =109.8 min) from readily accessible aryl(mesityl)iodonium salts. In this method, the aryl(mesityl)iodonium salt is treated rapidly with no-carrier-added [ C]CuCF or [ F]CuCF . The mesityl group acts as a spectator allowing radiolabeled trifluoromethylarenes to be obtained with very high chemoselectivity. Radiochemical yields from aryl(mesityl)iodonium salts bearing either electron-donating or electron-withdrawing groups at meta- or para- position are good to excellent (67-96 %). Ortho-substituted and otherwise sterically hindered trifluoromethylarenes still give good yields (15-34 %). Substituted heteroaryl(mesityl)iodonium salts are also viable substrates. The broad scope of this method was further exemplified by labeling a previously inaccessible target, [ C]p-trifluoromethylphenyl boronic acid, as a potentially useful labeling synthon. In addition, fluoxetine, leflunomide, and 3-trifluoromethyl-4-aminopyridine, as examples of small drug-like molecules and candidate PET radioligands, were successfully labeled in high yields (69-81 %).
迫切需要高效的方法来标记芳基三氟甲基基团，以提供用于正电子发射断层扫描 (PET) 生物医学研究的新型放射性示踪剂。我们报告了一种广泛适用于用碳-11（t =20.4 min）或氟-18（t =109.8 min）标记三氟甲基芳基的方法，该方法可从易得的芳基（均三甲苯基）碘鎓盐进行。在该方法中，芳基（均三甲苯基）碘鎓盐与无载体添加的 [ C]CuCF 3 或 [ F]CuCF 3 快速反应。均三甲苯基基团作为旁观者，允许以非常高的化学选择性获得放射性标记的三氟甲基芳基。带有供电子或吸电子基团的间位或对位芳基（均三甲苯基）碘鎓盐的放射化学产率良好至优秀（67-96％）。邻位取代的和其他空间位阻较大的三氟甲基芳基仍能获得良好的产率（15-34％）。取代的杂芳基（均三甲苯基）碘鎓盐也是可行的底物。该方法的广泛适用性进一步通过标记以前无法获得的靶标 [ C]p-三氟甲基苯硼酸来例证，该靶标可能是一种有用的标记合成子。此外，氟西汀、来氟米特和 3-三氟甲基-4-氨基吡啶作为小药物样分子和候选 PET 放射性配体的实例，以高产率（69-81％）成功标记。
