Phyllolactones A–E: new bishomoscalarane sesterterpenes from the marine sponge Phyllospongia lamellosa

Five new bishomoscalarane sesterterpenes, phyllolactones A–E (1–5), have been isolated from the marine sponge Phyllospongia lamellosa. The structures were elucidated by 1D and 2D 1H and 13C NMR, unambiguous assignments of overlapping 1H and 13C resonances were made by analysis of an HSQC–TOCSY spectrum, and relative stereochemistry established by analysis of coupling constants and ROESY and NOESY spectra. A summary of previously reported carbolactone-containing bishomoscalarane structures and the range of 13C chemical shifts arising from the various oxy substituents at C-3, C-12, C-16, C-20 and C-24 is included. Phyllolactones A–E modestly inhibit HIV-1 envelope-mediated fusion in vitro with IC50s of ∼2 μM, and show negligible cytotoxicity toward the cell lines used in the fusion assay (BS-C-1 and NIH 3T3).