Perfluoroaryl Azide Staudinger Reaction: A Fast and Bioorthogonal Reaction

• Published in: Angewandte Chemie International Edition Vol. 56; no. 40; pp. 12117 - 12121
• Main Authors: Sundhoro, Madanodaya, Jeon, Seaho, Park, Jaehyeung, Ramström, Olof, Yan, Mingdi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.09.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aromatic compounds; Azides - chemistry; bioconjugation; bioorthogonal reactions; Bovine serum albumin; Cell surface; Chemistry; Chemistry, Multidisciplinary; D-Galactosamine; Fluorescent Dyes - chemistry; Fluorine Compounds - chemistry; Hydrolysis; Kinetics; metabolic labelling; Microscopy, Fluorescence; perfluoroaryl azides; Phosphine; Phosphines; Phosphines - chemistry; Physical Sciences; Polysaccharides; Polysaccharides - chemistry; Proton Magnetic Resonance Spectroscopy; Science & Technology; Serum albumin; Staudinger reaction; bioconjugation; CYCLOADDITION; bioorthogonal reactions; Staudinger reaction; ACID; perfluoroaryl azides; MECHANISM; CHEMISTRY; LIGATION; ARYL AZIDES; metabolic labelling
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201705346

We report a fast Staudinger reaction between perfluoroaryl azides (PFAAs) and aryl phosphines, which occurs readily under ambient conditions. A rate constant as high as 18 m−1 s−1 was obtained between methyl 4‐azido‐2,3,5,6‐tetrafluorobenzoate and methyl 2‐(diphenylphosphanyl)benzoate in CD3CN/D2O. Furthermore, the iminophosphorane product was stable toward hydrolysis and aza‐phosphonium ylide reactions. This PFAA Staudinger reaction proved to be an excellent bioothorgonal reaction. PFAA‐derivatized mannosamine and galactosamine were successfully transformed into cell‐surface glycans and efficiently labeled with phosphine‐derivatized fluorophore‐conjugated bovine serum albumin. Better, faster, stronger: Perfluoroaryl azides (PFAAs) react with aryl phosphines in a fast Staudinger reaction under ambient conditions to yield kinetically stable iminophosphorane products. This PFAA Staudinger reaction proved to be an excellent bioorthogonal reaction and was successfully applied to cell‐surface labeling.