Work

Site-Selective C(sp3)–H Functionalization of Di-, Tri-, and Tetrapeptides at the N-Terminus

Year: 2014

Type: article

Abstract: 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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja510233h

Authors: Wei Gong, Guofu Zhang, Tao Liu, Ramesh Giri, Jin-Quan Yu

Institution: Scripps Research Institute

Language: English

Topic: Catalytic C–H Functionalization Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: China Scholarship Council, National Institute of General Medical Sciences