Antibacterial Acylphloroglucinols from Hypericum olympicum

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.