Bioassay-directed fractionation using multidrug-resistant (MDR) Staphylococcus aureus resulted in the isolation of four new polyprenylated benzophloroglucinol derivatives, sampsoniones N-Q (1-4), and four known compounds, 7-epiclusianone (5) and sampsoniones B, L, and R, from the roots of Hypericum sampsonii. The structures of these compounds were established by analysis of spectroscopic data, and the structures of 4 and 5 were determined by single-crystal X-ray diffraction crystallography. In the bioassay, 7-epiclusianone (5) showed promising activity with a minimum inhibitory concentration (MIC) of 7.3 microM against the NorA overexpressing MDR S. aureus strain SA-1199B; the positive control antibiotic norfloxacin showed activity at MIC 100 microM.

New antibacterial acylphloroglucinols (1-5) were isolated and characterized from the aerial parts of the plant Hypericum olympicum L. cf. uniflorum. The structures of these compounds were confirmed by extensive 1D- and 2D-NMR experiments to be 4,6-dihydroxy-2-O-(3″,7″-dimethyl-2″,6″-octadienyl)-1-(2'-methylbutanoyl)benzene (1), 4,6-dihydroxy-2-O-(7″-hydroxy-3″,7″-dimethyl-2″,5″-octadienyl)-1-(2'-methylbutanoyl)benzene (2), 4,6-dihydroxy-2-O-(6″-hydroxy-3″,7″-dimethyl-2″,7″-octadienyl)-1-(2'-methylbutanoyl)benzene (3), 4,6-dihydroxy-2-O-(6″-hydroperoxy-3″,7″-dimethyl-2″,7″-octadienyl)-1-(2'-methylbutanoyl)benzene (4), and 4,6-dihydroxy-2-O-(6″,7″-epoxy-3″,7″-dimethyloct-2″-enyl)-1-(2'-methylbutanoyl)benzene (5). These new natural products have been given the trivial names olympicins A-E (1-5). All compounds were evaluated against a panel of methicillin-resistant Staph. aureus and multidrug-resistant strains of Staph. aureus. Compound 1 exhibited minimum inhibitory concentrations (MICs) of 0.5-1 mg/L against the tested Staph. aureus strains. Compounds 2 to 5 were also shown to be active, with MICs ranging from 64 to 128 mg/L. Compound 1 was synthesized using a simple four-step method that can be readily utilized to give a number of structural analogues of 1.

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The inhibitory effects of selected phenolic lichen substances were tested against a panel of methicillin- and multidrug-resistant Staphylococcus aureus. Depsidones with long alkyl chains on both of the aromatic rings were consistently active against the strains tested, comparable to or better than the level of clinically used antibacterial drugs. A similar level of activity was also observed for rhizocarpic acid. The previously described cytotoxic pentacyclic compound hybocarpone was by far the most active, exhibiting minimum inhibitory concentrations (MICs) of 4-8 microg/mL (8.13-16.3 microM) against a range of multidrug efflux pump expressing strains of S. aureus.