Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

ABSTRACT: The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective constructi

SUBMITTER: Cheng MJ 

PROVIDER: S-EPMC11245619 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature