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 peptid...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2014-12, Vol.136 (48), p.16940-16946
Main Authors: Gong, Wei, Zhang, Guofu, Liu, Tao, Giri, Ramesh, Yu, Jin-Quan
Format: Article
Language:English
Subjects:
Amino Acids - chemistry
Ligands
Molecular Conformation
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
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Summary: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(sp3)–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(sp3)–H activation toward postsynthetic modification of a broader range of peptides.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja510233h