(±)-Hippolide J - A Pair of Unusual Antifungal Enantiomeric Sesterterpenoids from the Marine Sponge Hippospongia lachne

A pair of enantiomeric sesterterpenoids, (+/-)-hippolide J (1a and 1b), were isolated from the marine sponge Hippospongia lachne collected from the South China Sea. The racemic mixture was resolved into a pair of enantiomers, (-)-1a and (+)-1b, by chiral HPLC separation. The structures of the enantiomers were determined through ESI-HRMS and NMR spectroscopic analysis, and their absolute configurations were determined by comparison between the calculated and experimental electronic circular dichroism (ECD) spectra. Hippolide J 1) features an unusual bicyclo[4.2.0] octene core and contains three functional groups, namely, a hydroxymethyl group, an alpha,beta-unsaturated gamma-lactone fragment, and a characteristic prenyl side-chain. The evaluation of the antifungal activity of (-)-1a and (+)-1b revealed that both show potent antifungal activity against three strains of hospital-acquired pathogenic fungi, namely, Candida albicans SC5314, Candida glabrata 537, and Trichophyton rubrum Cmccftla, with MIC50 9minimum concentration to give 50 % inhibition) values of 0.125-0.25 mu g/mL.