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Synthesis and Diversification of Macrocyclic Alkynediyl Sulfide Peptides
Author(s) -
Godin Éric,
Nguyen Thanh Sacha,
GuerreroMorales Javier,
Santandrea Jeffrey,
Caron Antoine,
Minozzi Clémentine,
Beaucage Noémie,
Rey Bastien,
Morency Mathieu,
AbelSnape Xavier,
Collins Shawn K.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003655
Subject(s) - cycloaddition , tripeptide , chemistry , combinatorial chemistry , halide , sulfide , catalysis , peptide synthesis , alkyne , peptide , stereochemistry , organic chemistry , biochemistry
The synthesis of rare macrocyclic alkynediyl sulfides by a Cu‐catalyzed C sp −S cross‐coupling is presented. The catalytic protocol (Cu(MeCN) 4 PF 6 /dtbbpy) promotes macrocyclization of peptides, dipeptides and tripeptides at ambient temperature (14 examples, 23→73 % yields) via thiols and bromoalkynes, and is chemoselective with regards to terminal alkynes. Importantly, the underexplored alkynediyl sulfide functionality incorporates a rigidifying structural element and opens new opportunities for diversification of macrocyclic frameworks through S oxidation, halide addition and azide–alkyne cycloaddition chemistries to integrate sulfones, halides or valuable fluorophores (7 examples, 37→92 % yields).