Convenient PET-tracer production via SuFEx 18F-fluorination of nanomolar precursor amounts

Recent Advances in 18F-Labeled Amino Acids Synthesis and Application

“…A considerably low bone radioactivity uptake (maximum SUV bw 155 ± 43, 90–120 min p.i.) indicated the high stability of [ 18 F] 21 against in vivo defluorination ( Figure 22 b,c) [ 80 ]. Therefore, SuFEx radiofluorination shows potential to accelerate the development of novel AA PET tracers.…”

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. ,,, …”

“…For compounds featuring an S–F bond that have been applied to 18 F-radiochemistry, the majority feature either alkyl or aryl sulfonyl [ 18 F]fluorides or aryl [ 18 F]fluorosulfonates, with only a limited amount featuring sulfamoyl [ 18 F]fluorides. ,,− It has been reported that aryl [ 18 F]fluorosulfonates possess superior stability, compared to the alkyl or aryl sulfonyl fluorides, due to the change in electrophilicity of the sulfur atom by the additional oxygen atom. , However, due to this, they generally possess lower metabolic stability. Recent literature has demonstrated the ability to synthesize alkyl and aryl sulfonyl [ 18 F]fluorides in high radiochemical yields; however, the low metabolic stability of the S–F bond has limited the applications of sulfonyl fluorides and therefore warrant further investigations. ,, While a 2,4,6-triisopropylbenzenesulfonyl [ 18 F]fluoride was shown to be stable in rat serum over 2 h, it is unclear whether this was solely due to electron donation or if steric hindrance aided the stability.…”

Direct 18F-Fluorosulfurylation of Phenols and Amines Using an [18F]FSO2+ Transfer Agent Generated In Situ

“…10 The Sharpless group also independently employed isotopic exchange to generate 18 F-aryl fluorosulfates in high radiochemical yields (RCYs), 11 along with a recent development from the Neumaier group. 12 However, isotopic functionalization directly from phenols and amines to construct radioactive fluorine−sulfur scaffolds has not yet been reported.…”

“…Subsquently, 18 F/ 19 F isotopic exchange was employed to produce 18 F-labeled sulfamoyl fluorides from their corresponding nonradioactive sulfamoyl precursors . The Sharpless group also independently employed isotopic exchange to generate 18 F-aryl fluorosulfates in high radiochemical yields (RCYs), along with a recent development from the Neumaier group . However, isotopic functionalization directly from phenols and amines to construct radioactive fluorine–sulfur scaffolds has not yet been reported.…”