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

Abstract

Synthesis of sulfamoyl [18F]­fluorides has been a challenging topic owing to the inefficient nucleophilic radiofluorination of sulfamoyl derivatives. Herein, we report an 18F/19F isotopic exchange approach to synthesize various sulfamoyl [18F]­fluorides, otherwise inaccessible via direct synthesis from amines, with high radiochemical yields up to 97% (30 examples). This late-stage labeling protocol offers an efficient route to yield functionalized molecules by diversifying the chemical library possessing sulfamoyl functionalities through nucleophilic 18F incorporation within nitrogen-containing sulfur­(VI) frameworks.

Study of Carbamoyl Fluoride: Synthesis, Properties and Applications

“…Compared to results for sulfamoyl fluorides described in the literature, [19a] the labeling of carbamoyl fluorides by 18 F/ 19 F isotopic exchange seems to be competitive.…”

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

“…18 F-labeled acetaminophen analog was automated radio-synthesized in 9% of decay-corrected RCY with the molar activity of 42 GBq/μmol (Mode 1) and 22% of decay-corrected RCY with the molar activity of 55 GBq/μmol (Mode 2). Based on previous works, Chun, Hong, and co-workers radio-synthesized sulfamoyl [ 18 F]fluorides by the 18 F– 19 F exchange method ( Jeon et al, 2021 ). 18 F-labeled amoxapine derivative of sulfamoyl fluoride was automated radio-synthesized in 53% of RCY with 56 GBq/μmol ( Figure 5 ).…”

An Investigation into the In Vitro Metabolic Stability of Aryl Sulfonyl Fluorides for their Application in Medicinal Chemistry and Radiochemistry

“…Since the development of sulfur(VI) fluoride exchange (SuFEx) chemistry by the Sharpless group, uses of the sulfur–fluorine (S–F) bond moieties including alkyl or aryl sulfonyl fluorides (SO 2 –F), fluorosulfonates (O–SO 2 –F) and sulfamoyl fluorides (N–SO 2 –F), have gained increasing interest in synthetic chemistry, medicinal chemistry, and other biological applications. − Their ease of synthesis and unique reactivity in various media have led to molecules containing S–F bond moieties being used as covalent protein inhibitors, biological probes, fluorinating reagents and 18 F-radiolabeling molecules (Figure ). − In fluorine-18 radiochemistry, sulfonyl fluorides, fluorosulfonates, and sulfamoyl fluorides have been investigated and used as radiolabeled molecules for positron emission tomography (PET) and as radiofluoride relay reagents. ,,− Use of these functional groups in radiochemistry is interesting because while the S–F bond moiety has been reported to be relatively unreactive to nucleophilic substitution, including hydrolysis, under certain biological conditions sulfonyl fluorides and fluorosulfonates becomes reactive, resulting in the breakdown of the S–F bond and defluorination. ,,, …”