Iodinated Meroditerpenes from a Red Alga Callophycus sp.

Unique iodine-containing meroditerpenes iodocallophycoic acid A ( 1 ) and iodocallophycols A–D ( 2 – 5 ) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2 S,6 S,7 S,10 S,14 S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F ( 6 ) and bromophycoic acid A methyl ester ( 7 ), were evaluated for relevant human disease targets. Iodocallophycoic acid A ( 1 ) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL –1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL –1 .