Work

Chemoselective C-Terminal Activation Platform for Direct Conversion of Native Linear Peptides into Thiazoline/Thiazole Macrocycles

Year: 2026

Type: article

Abstract: We report a sequence-independent, chemoselective C-terminal activation platform to synthesize thiazoline/thiazole macrocycles from native linear peptides. Selective C-terminal primary amide-to-nitrile conversion proceeds in solution on fully unprotected peptides with broad functional-group compatibility. This approach eliminates the need for presynthesized α-amino nitrile building blocks and minimizes epimerization risk. Our method enables rapid macrocyclization, supporting the direct total syntheses of Mollamide F, Sanguinamide A, and Haligramide A from linear precursors.

Source: Organic Letters

DOI: 10.1021/acs.orglett.6c01073

Authors: Bao Quang Gia Le, Minyoung Kwon, Monika Raj

Institution: Emory University

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: $4,500

Funders: National Science Foundation, National Institutes of Health, National Human Genome Research Institute, Division of Chemistry