Streefkerk, Dieuwertje E. Schmidt, Marcel Ippel, Johannes H. Hackeng, Tilman M. Nuijens, Timo Timmerman, Peter H. van Maarseveen, Jan Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner. model peptides;multicyclic peptides;Consecutive CEPS;molecule class;Enzymatic macrocyclization;tetracyclic peptides;one-pot scaffold-assisted cyclizations;oxime ligation;Constrained Tetracyclic Peptides;CLIPS alkylation;chemical methodologies;Oxime Ligation;21 tetracyclic peptides 2019-03-26
    https://acs.figshare.com/articles/journal_contribution/Synthesis_of_Constrained_Tetracyclic_Peptides_by_Consecutive_CEPS_CLIPS_and_Oxime_Ligation/7893440
10.1021/acs.orglett.9b00378.s001