Sulfonium Salts as Leaving Groups for Aromatic Labelling of Drug-like Small Molecules with Fluorine-18

摘要: Positron emission tomography (PET) is unique in that it allows quantification of biochemical processes vivo, but difficulties with preparing suitably labelled radiotracers limit its scientific and diagnostic applications. Aromatic [18F]fluorination drug-like small molecules particularly challenging as their functional group compositions often impair the labelling efficiency. Herein, we report a new strategy for incorporation 18F into highly functionalized aromatic compounds using sulfonium salts leaving groups. The method compatible pharmacologically relevant groups, including aliphatic amines basic heterocycles. Activated substrates react [18F]fluoride at room temperature, heating reaction proceeds presence hydrogen bond donors. Furthermore, use electron rich spectator ligands efficient regioselective non-activated moieties. provides broadly applicable route biologically active molecules, offers immediate practical benefits drug discovery imaging PET.