title: Efficient synthesis of [18F]FPyME: A new approach for the preparation of maleimide-containing prosthetic groups for the conjugation with thiols.
abstract: An improved high yielding radiosynthesis of the known thiol-reactive maleimide-containing prosthetic group1-[3-(2-[18F]fluoropyridine-3-yloxy)propyl]pyrrole-2,5-dione ([18F]FPyME) is described. The target compound was obtained by a two-step one-pot procedure starting from a maleimide-containing nitro-precursor that was protected as a Diels-Alder adduct with 2,5-dimethylfurane. Nucleophilic radiofluorination followed by heat induced deprotection through a Retro Diels Alder reaction yielded, after chromatographic isolation, [18F]FPyME with a radiochemical yield of 20% in about 60 min overall synthesis time. A variety of other [18F]fluoropyridine based maleimide-containing prosthetic groups should be accessible via the described synthetic strategy.
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Cavani
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bier
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Holschbach
authors.affiliation: Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
mesh_terms: D008301:Maleimides / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013388:Succinimides / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: C540937:1-(3-(2-fluoropyridin-3-yloxy)propyl)pyrrole-2,5-dione; D008301:Maleimides; D011725:Pyridines; D019275:Radiopharmaceuticals; D013388:Succinimides; D013438:Sulfhydryl Compounds
keywords: PET chemistry; [18F]FPyME; fluorine-18; maleimide prosthetic group; protein labelling; thiol reactive reagent