Antibacterial Acylphloroglucinols from Hypericum olympicum.

Abstract

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.