Morphing Natural Product Platensimycin via Heck, Sonogashira, and One-Pot Sonogashira/Cycloaddition Reactions to Produce Antibiotics with In Vivo Activity.

ABSTRACT: Type II fatty acid synthases are promising drug targets against major bacterial pathogens. Platensimycin (PTM) is a potent inhibitor against β-ketoacyl-[acyl carrier protein] synthase II (FabF) and β-ketoacyl-[acyl carrier protein] synthase I (FabB), while the poor pharmacokinetics has prevented its further development. In this work, thirty-two PTM derivatives were rapidly prepared via Heck, Sonogashira, and one-pot Sonogashira/cycloaddition cascade reactions based on the Gram-scale synthesis of 6-iodo PTM (4). About half of the synthesized compounds were approximately equipotent to PTM against the tested Staphylococcus aureus strains. Among them, the representative compounds 4, A4, and B8 exhibited different plasma protein binding affinity

SUBMITTER: Deng Y 

PROVIDER: S-EPMC9027111 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature