C-H radiocyanation of bioactive molecules via sequential iodination/copper-mediated cross-coupling

• Published in: Chemical science (Cambridge) Vol. 14; no. 43; pp. 12068 - 12072
• Main Authors: Horikawa, Mami, Joy, Stephen T, Sharninghausen, Liam S, Shao, Xia, Mapp, Anna K, Scott, Peter J H, Sanford, Melanie S
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 08-11-2023; The Royal Society of Chemistry
• Subjects: Amino acids; Chemistry; Copper; Coupling (molecular); Cross coupling; Iodination; Substrates; Tryptophan; Tyrosine; Uracil
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc03948j

This report describes a net C-H radiocyanation reaction for the transformation of electron rich (hetero)aromatic substrates into
CN-labeled products. Electrophilic C(sp
)-H iodination of the (hetero)arene with
-iodosuccinimide is followed by Cu-mediated radiocyanation with K
CN. 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.