First total synthesis and antimicrobial evaluation of xanthone V1

Antibiotic resistance demands new agents. We disclosed the first total synthesis of the natural xanthone V1 (1), which featured a regioselective Claisen cyclization and a Claisen/Cope rearrangement that installed the pyran ring and isopentenyl unit. The synthetic compound showed moderate antibacterial potency (MICs 16-64 μg/ml) across multiple strains and synergized with ciprofloxacin against MRSA. It exhibited low cytotoxicity toward mammalian cells and minimal hemolysis, thereby supporting xanthone V1 as a promising lead for anti-MRSA therapy.