Work

Total Synthesis of Discobahamin A and Putative Structure of Discobahamin B via an Isocyanide‐based Macrocyclization Reaction

Year: 2025

Type: article

Abstract: We report in this paper the first total synthesis of discobahamin A, a 24‐membered macrocyclopeptide containing an α ‐keto amide functional group. We assign the absolute configuration of 2‐hydroxy‐3‐methylpentanoic acid (Hmp), the side chain capping the N‐terminus of the macrocycle, as the (2 S , 3 S ) stereoisomer. A novel macrocyclization strategy was developed, utilizing an intramolecular Passerini reaction between ω ‐isocyano aldehyde and acetic acid. Notably, this macrocyclization proceeds via C(sp 3 )‐C(sp 2 ) bond formation and de novo generation of an α ‐keto amide functional group. Furthermore, we synthesized both the proposed structure of discobahamin B and its diastereomer. However, the spectroscopic data for these two compounds do not fully align with those reported for discobahamin B.

Source: Angewandte Chemie

DOI: 10.1002/ange.202419383

Authors: Baochao Yang, Qian Wang, Jieping Zhu

Institution: École Polytechnique Fédérale de Lausanne

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: $5,790

Funder: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung