A Multifunctional Sulfur(VI) Fluoride for SuFEx Reactions: N-CF2H Sulfamoyl Fluorides
Yali Long1, Xingjin He1, Wencheng Zhong1
1Department: Department of Nuclear Medicine, Institution: First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
None:
Sulfur(VI) fluorides based on sulfur(VI) fluoride exchange (SuFEx) chemistry have demonstrated their unique versatility and high efficiency in the field of medicinal chemistry. Acting as both covalent and hydrogen bond donors, the novel N-CF2H sulfamoyl fluoride will enhance the binding strength between drugs and receptors in organism, thereby injecting new vitality into the research of targeted drugs. Herein, we report the two-step synthesis of N-CF2H sulfamoyl fluorides from primary amines via successive fluorosulfonylation and insertion of difluorocarbene. This method shows broad scope, provides a platform for rapidly generating N-CF2H sulfamoyl fluorides by virtue of the diversity and availability of amines. The stability of N-CF2H sulfamoyl fluorides was tested in aqueous environment at different pH, showing that most compounds remained >95% intact for 72 h. As a novel SuFEx building block, N-CF2H sulfamoyl fluoride shows chemoselectivity toward phenol and does not react with amines and alcohols. Besides, N-CF2H sulfamoyl fluorides were subjected to debenzylation and amide-bond-formation reactions to generate peptides, Sitagliptin derivative and bioactive alkylamine. Finally, N-CF2H sulfamoyl fluoride underwent successful F-18 labeling. With the reported syntheses, we believe that N-CF2H sulfamoyl fluoride will soon be practically applied in drugs, covalent targeted radioligand, F-18 PET tracers, electrolyte in general.
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