Biologically Active Sesterterpenes from a New Caledonian

Chemical investigations of marine sponges from the genus Hyrtios has yielded a predominance of scalarane-type sesterterpenes.' We have previously isolated heteronemin and the new 12-epi-heteronemin as representatives of this class of sesterterpenes, from the marine sponge Hyrtìos erecta collected in New Caledonia? However, both scalarane-type sesterterpenes and those of the manoalide family have been clearly shown to Co-occur in a sample of Hyrtios erecta, collected at Amani Island, Japan? In our continuing chemical investigation of sponges from New Caledonia, we studied Hyrtios sp. which contained only sesterterpenes of the manoalide family as major constituents. In this paper we report on the isolation and structure elucidation of thorectolide monoacetate 1 and thorectolide 2. By HMQC and HMBC experiments we corrected the 13C NMR assignment of C-5 and we assigned the resonances of ' carbons C-8, C-12 and C-16 of thorectolide monoacetate, previously isolated from the sponge Thorectandra ex cava tu^.^ We also investigated the stereochemistry at C-4 and C-24. Both Hyrtìos sesterterpenes provide a further example of secondary metabolite variation within the Hyrtios genus. Fractionation of the CHzCll extract of Hyrtios sp., which exhibited in a preliminary pharmacological screening significant antimicrobial activity against S. aurem and cytotoxic activity against Kl3 cells, was monitored by an antimicrobial bioassay using S. aureus. The CHC13-MeOH 955 fraction, which retained maximum activity, was successively subjected to Sephadex LH-20 (CHC1,-MeOH, 2 8 v/v) and silica gel (hexane-EtOAc, 7:3 vlv) column chromatography to afford thorectolide monoacetate 1 and thorectolide 2. The known heteronemin and 12-epiheteronemin was not detected in the CH2C12 extract of this sponge. Compound 1 was obtained as an optically active pale yellow glass, [alD = +33.8" (c 0.49, CHC1,). The formula