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Backbone‐Enabled Directional Peptide Macrocyclization through Late‐Stage Palladium‐Catalyzed δ‐C(sp 2 )−H Olefination
Author(s) -
Bai Zengbing,
Cai Chuangxu,
Yu Zonglun,
Wang Huan
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807953
Subject(s) - peptidomimetic , peptide , palladium , chemistry , combinatorial chemistry , stereochemistry , catalysis , bicyclic molecule , cyclic peptide , phenylalanine , amino acid , organic chemistry , biochemistry
C−H activation methods for peptide macrocyclization have the potential to provide peptidomimetics and cyclic peptides with expanded structural diversity. Now, a highly versatile peptide macrocyclization strategy via late‐stage palladium‐catalyzed δ‐C(sp 2 )−H olefination of phenylalanine residues has been developed. This method utilizes peptide backbone amides as internal directing groups and allows facile macrocyclization of peptides in the N‐to‐C direction. Combined with the previously developed β‐C(sp 3 )−H arylation method for peptide macrocyclization in the C‐to‐N direction, a pair of palladium‐catalyzed reactions were obtained that are directionally orthogonal, and the first example of one‐pot synthesis of bicyclic peptides via Pd‐catalyzed β‐C(sp 3 )−H and δ‐C(sp 2 )−H activation is demonstrated.