Efficient synthesis of [18 F]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-[¹⁸ F]fluoropyridine-3-yloxy)propyl]pyrrole-2,5-dione ([¹⁸ F]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, [¹⁸ F]FPyME with a radiochemical yield of 20% in about 60 min overall synthesis time. A variety of other [¹⁸ F]fluoropyridine based maleimide-containing prosthetic groups should be accessible via the described synthetic strategy.

Keywords: PET chemistry; [18F]FPyME; fluorine-18; maleimide prosthetic group; protein labelling; thiol reactive reagent.