Work

Site-selective alcoholysis of oligopeptides through N-alkylation of a secondary amide unit by cooperative catalysis

Year: 2025

Type: article

Abstract: ABSTRACT We disclose a one-pot two-step protocol for site-selective cleavage of C–N bonds within oligopeptides. We demonstrate that by exploiting the cooperative functions of Sc(OTf) 3 and Barton’s base, N -alkylation of the oligopeptide’s specific secondary amide unit can be achieved. The resulting tertiary amide is “twisted” due to steric factors; its C–N bond is weakened by the disruption of amide resonance. Thus, when the oligopeptide derivative is subjected to Brønsted acid-mediated alcoholysis, only the N -alkylated residue undergoes C–N bond cleavage to afford an ester and an amine, while its secondary amides remain intact. Investigations aimed at elucidating the factors that influence the observed site-selectivity are described.

Source: Tetrahedron

DOI: 10.1016/j.tet.2025.134685

Authors: Yuankai Wang, Cunyuan Zhao, Masayuki Wasa

Institutions: The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Scripps Research Institute

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,680

Funders: National Science Foundation, Division of Chemistry