Antibacterial Prenylated Acylphloroglucinols from <i>Psorothamnus fremontii</i>

Abstract

Psorothatins A–C (<b>1</b>–<b>3</b>), three antibacterial prenylated acylphloroglucinol derivatives, were isolated from the native American plant <i>Psorothamnus fremontii</i>. They feature an unusual α,β-epoxyketone functionality and a β-hydroxy-α,β-unsaturated ketone structural moiety. The latter forms a pseudo-six-membered heterocyclic ring due to strong intramolecular hydrogen bonding, as indicated by the long-range proton–carbon correlations in the NMR experiments. Psorothatin C (<b>3</b>) was the most active compound against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococcus faecium</i>, with IC₅₀ values in the range 1.4–8.8 μg/mL. The first total synthesis of <b>3</b> described herein permits future access to structural analogues with potentially improved antibacterial activities