The Configurations And Bioactivities Of Marine-derived New Xanthones

Marine-derived microbes,which have become a hotspot in recent years,are an important source of marine natural products and marine medicines..Due to the special ecological environment of the ocean,the metabolic pathway of marine organisms has certain peculiarities,and its metabolites have novel structure and unique activity.It is particularly important to note that the same strain of fungi can produce compounds of different chemical structures under different conditions.There have been many reports in the literature that a series of drugs and lead compounds for the treatment of major human diseases are found in the metabolites of marine-derived microorganisms.16 Isoprene xanthones?C-4 terpenoid-derived side chain?monomer compounds?1-16?were obtained from the fungus Aspergillus sp.ZA-01 using the two fermentation modes,of which 1-8,10-12 were new compounds.Their planar structures and relative configurations were determined by 1D and 2D NMR data.The congurations of C-14 and C-15 in prenylxanthone derivatives were challenging to be assigned due to the high conformational flexibility of the terpenoid-derived side chains.It was un-accommodated to determine the relative con guration of C-14 and C-15 by comparison of the coupling constants(J_14,15)as the free rotation of the flexible side chain.This work demonstrated that using multiple chiroptical methods in combination with DFT calculations allowed one to determine absolute congurations with high condence for chiral natural products,which possessed rotatable bonds.The study showed that more than one chiral method can be combined as the first choice for stereotactic characterization of flexible molecules.Compounds 1-16 were evaluated for their cytotoxic and antibacterial activities.Among them,6 showed cytotoxicity against the A-549 cell line with the IC₅₀ value of 1.1?M,and 7exhibited antibacterial activity against Micrococcus lysodeikticus with the MIC value of 0.78?g/mL.Compound 10 showed the strongest anti-Vibrio activity against Vibrio parahemolyticus?MIC=1.56?M?,Vibrio anguillarum?MIC=1.56?M?,and Vibrio alginolyticus?MIC=3.12?M?.In addition,eight known monomeric compounds?17-24?were isolated from the fungus Aspergillus versicolor.The structures of the isolated compounds were determined by 1D and2D NMR spectroscopy.In summary,the new natural products with good biological activity were obtained from the fungus Aspergillus sp.ZA-01.The absolute configurations of the compounds was determined by spectroscopy and quantum chemical calculation.Activity experiments showed that some compounds had high activity against certain pathogenic bacteria,which provides a basis for the development and application of drug leading compounds.