Reflecting recent work in the Mapp Group

In a collaborative work, published in Chemical Science, between the Mapp and Sanford groups, and researchers at the Department of Radiology, all at the University of Michigan, authors describe a net C–H radiocyanation reaction for the transformation of electron rich (hetero)aromatic substrates into ¹¹CN-labeled products. Electrophilic C(sp²)–H iodination of the (hetero)arene with N-iodosuccinimide is followed by Cu-mediated radiocyanation with K¹¹CN.

This sequence is applied to a variety of substrates, including the nucleobases uracil and cytosine, the amino acids tyrosine and tryptophan, and the peptide LYRAGWRAFS, which undergoes selective C–H radiocyanation at the tryptophan (W) residue.

This transformation is operationally simple, proceeds smoothly with peptides, and can be conducted in automated in a commercial radiosynthesis module, substrates 18-¹¹CN and 21-¹¹CN. It provides a straightforward approach to selectively introducing a ¹¹CN moiety on tryptophan residues in a peptide containing multiple other aromatic amino acids without the need to synthesize dedicated labelling precursors.

Ongoing work is focused on applying this method to the ¹¹CN-radiolabeling of various bioactive molecules of interest to the group's PET imaging program, including proteins.

The authors gratefully acknowledge The National Institutes of Health, R01EB021155, for supporting this work. Additionally they thank Dr Eric Webb and Dr Tanpreet Kaur for the preparation of K¹¹CN solutions, Dr Allen Brooks for helpful discussions, and Dr Mónica Rivas for helping with purification of several compounds.