cs9b05074_si_001.pdf (13.37 MB)
Zn-Catalyzed Nicotinate-Directed Transamidations in Peptide Synthesis
Version 2 2021-06-14, 15:41
Version 1 2020-03-20, 13:08
journal contribution
posted on 2021-06-14, 15:41 authored by Charlie Hollanders, Evelien Renders, Charlène Gadais, Dario Masullo, Laurent Van Raemdonck, Clarence C. D. Wybon, Charlotte Martin, Wouter A. Herrebout, Bert U. W. Maes, Steven BalletA chemoselective and catalytic transamidation for peptide synthesis
is described. Transamidation under Zn catalysis is chemoselectively
achieved by amino acid amide/peptidic amide derivatization with a tert-butyl nicotinate (tBu-nic) directing
group. The directing group could be easily introduced on protected
amino acid amides via Pd-catalyzed amidation with tert-butyl 2-chloronicotinate (tBu-nicCl). Under standard
peptide coupling/deprotection conditions, the tBu-nic-equipped
amino acid amides proved to be fully inert, allowing them to be easily
built-in in complex molecules. The disclosed method was evaluated
in the synthesis of diverse dipeptides, in dipeptide segment coupling,
in side-chain modification of a solid-supported tetra-/pentapeptide,
and in the macrocyclization of a heptapeptide.