Synthesis of ¹⁸F-Labeled Aryl Fluorosulfates via Nucleophilic Radiofluorination

Abstract

Sulfuryl fluoride gas is a key reagent for SO2F transfer. However, conventional SO2F transfer reactions have limited 18F-radiochemistry translation, due to the inaccessibility of gaseous [18F]­SO2F2. Herein, we report the first SO2F2-free synthesis of aryl [18F]­fluorosulfates from both phenolic and isolated aryl imidazylate precursors with cyclotron-produced 18F–. The radiochemical yields ranged from moderate to good with excellent functional group tolerance. The reliability of our approach was validated by the automated radiosynthesis of 4-acetamidophenyl [18F]­fluorosulfate.

Late-Stage 18F/19F Isotopic Exchange for the Synthesis of 18F-Labeled Sulfamoyl Fluorides

“…Recently, we reported a direct radiofluorosulfurylation method to produce aryl [ 18 F]fluorosulfates from phenols using 1,1′-sulfonyldiimidazole (SDI) and cyclotron-produced 18 F − (Figure 1b). 15 Unlike direct radiosulfurylative activation from phenols, the generation of 18 F-labeled aryl fluorosulfates was also achieved from aryl fluorosulfate precursors via isotopic exchange. 16 In our initial studies, we attempted direct radiofluorosulfurylation of amines to ascertain whether the corresponding 18 F-labeled sulfamoyl fluoride could be synthesized.…”

Fluorine-18: Radiochemistry and Target-Specific PET Molecular Probes Design

“…18 F-labeled olaparib analog was successfully radio-synthesized in 32% of RCY with the molar activity of 280 GBq/μmol. Aryl [ 18 F]fluorosulfates were also successfully radio-synthesized in two modes by Chun, Hong, and co-workers ( Kwon et al, 2020 ). The radiofluorination modes include the direct one-pot radiofluorosulfurylation of phenolic precursors (Mode 1) and the radiofluorination of isolated imidazylates (Mode 2).…”

Reaction of [18F]Fluoride at Heteroatoms and Metals for Imaging of Peptides and Proteins by Positron Emission Tomography

“…Furthermore, they show excellent stability in vivo . Recently, Kwon et al also reported the synthesis of fluorine-18 radiolabeled aryl fluorosulfates from their aryl imidazylate precursors ( 89 ) ( Kwon et al, 2020 ). In comparison, fluorination was performed at high temperatures but greater than 50% yields were frequently obtained with only a few exceptions ( Figure 14 ).…”