Switching Residues: A Platform for the Synthesis of Fidaxomicin Antibiotics.

ABSTRACT: Peripheral modification is often the main approach to optimize natural products for improved biological activity or desired physicochemical properties. This procedure inevitably increases molecular weight, often accompanied by undesired increased lipophilicity. Removing structural elements from natural products is not always tolerated. This is also the case for the antibiotic fidaxomicin (Fdx), where every structural component has been shown to be crucial for antibiotic activity. In this work, we demonstrate how the residue switching approach can maintain biological activity of Fdx derivatives by replacing the rhamnoside-dichlorohomoorsellinate moiety of Fdx with smaller, more polar building blocks. We used palladium-catalysed allylic substitution to selectively install N-nucleophiles on t

SUBMITTER: Jung E 

PROVIDER: S-EPMC11811690 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature