Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the N-terminus.
Although the syntheses of novel and diverse peptides rely mainly on traditional coupling using unnatural amino acids, postsynthetic modification of peptides could provide a complementary method for the preparation of nonproteinogenic peptides. Site selectivity of postsynthetic modification of peptides is usually achieved by targeting reactive moieties, such as the thiol group of cysteine or the C-2 position of tryptophan. Herein, we report the development of site-selective functionalizations of inert C(sp(3))-H bonds of N-terminal amino acids in di-, tri-, and tetrapeptides without installing a directing group. The native amino acid moiety within the peptide is used as a ligand to accelerate the C-H activation reaction. In the long run, this newly uncovered reactivity could provide guidance for developing site-selective C(sp(3))-H activation toward postsynthetic modification of a broader range of peptides.
Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Wei
W
Gong
Guofu
G
Zhang
Tao
T
Liu
Ramesh
R
Giri
Jin-Quan
JQ
Yu
D000596:Amino Acids / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*
D000596:Amino Acids; D008024:Ligands; D009842:Oligopeptides