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Palladium‐Mediated Arylation of Lysine in Unprotected Peptides
Author(s) -
Lee Hong Geun,
Lautrette Guillaume,
Pentelute Bradley L.,
Buchwald Stephen L.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611202
Subject(s) - chemistry , palladium , lysine , amino acid , peptide , cyclic peptide , molecule , side chain , nucleophile , aryl , combinatorial chemistry , peptide bond , selectivity , nucleophilic substitution , stereochemistry , organic chemistry , catalysis , biochemistry , polymer , alkyl
A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine‐supported palladium(II)–aryl complex and a weak base, lysine amino groups underwent C−N bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.