Direct 11CN-Labeling of Unprotected Peptides via Palladium-Mediated Sequential Cross-Coupling Reactions
† Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States
‡ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, United States
§ Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States
A practical procedure for 11CN-labeling of unprotected peptides has been developed. The method was shown to be highly chemoselective for cysteine over other potentially nucleophilic residues, and the radiolabeled products were synthesized and purified in less than 15 min. Appropriate for biomedical applications, the method could be used on an extremely small scale (20 nmol) with a high radiochemical yield. The success of the protocol stems from the use of a Pd-reagent based on a dihaloarene, which enables direct “nucleophile–nucleophile” coupling of the peptide and [11C]cyanide by temporal separation of nucleophile addition.
J. Am. Chem. Soc., Article ASAP
DOI: 10.1021/jacs.7b02761
Publication Date (Web): May 15, 2017
