Studies On Four Marine Invertebrates:Chemical Composition,Chemical Ecology And Bioactivities

Marine invertebrates are rich sources of secondary metabolites with complex/intriguing chemical diversities and a wide spectrum of biological activities.In recent years,these animals have received extensive attention and become a research hotspot.There is sufficient evidence that marine invertebrates can use bioactive secondary metabolites as defense chemicals to escape predators.A series of interesting results have been obtained through the research on the chemistry,chemical ecology and pharmacology of marine invertebrates,which play an important role in the research of new drugs and the discovery of new lead compounds.In the process of searching for marine bioactive secondary metabolites,we systematically studied the chemical constit-uents,chemical ecology and biological activities of two species of mollusks 1placobranchus ocellatus and Onchidium sp.),one species of soft corals(Lobophytum sp.)collected from the South China Sea,and one species of soft corals(litophyton setoensis)collected from Bali Sea.A total of 99 compounds were isolated from the above four biological samples by using silica gel column chromatography,reverse phase silica gel column chromatography,Sephadex LH-20 gel column chromatography and reversed-phase high performance liquid chromatography.Among them,40 of them were new compounds,2 of them were herein described as new natural products for the first time,and eight complex polypropionates with three types of unprecedented carbocyclic skeletons.In addition,nine compounds were derived,two of which have an unprecedented diterpene carbon skeleton.The structures of these new compounds were elucidated by extensive spectroscopic analysis,single-crystal X-ray diffraction analysis,and quantum mechanical(QM)-NMR methods.The absolute configurations of some new compounds were determined by the application of the modified Mosher’s method,the X-ray diffraction analysis using Cu/Ga Kα radiation,TDDFT-ECD calculation,and chemical transformation.In the following extensive biological activity screening experiments,some compounds with good biological activities were found.This results not only enrich the diversity of chemical composition of marine invertebrates,but also provide a basis for further research and utilization.In this study,the chemical investigation of P.ocellatus from the South China Sea had led to the discovery of 43 compounds(±)-1-1-1-26,including 17 enantiomers((±)-1-1-(±)-1-17).Among them,(±)-1-1-(±)-1-4 are the non-y-pyrone polyketides with novel skeletons.The absolute configurations of(±)-1-1-(±)-1-12 were determined by TDDFT-ECD calculation,while the absolute configurations of(±)-1-13-(±)-1-17 were determined by comparing their ECD spectra with those of(±)-1-12.The possible biosynthetic pathway of compound(±)-1-1-(1)-1-4 was reasonably deduced,and compounds(±)-1-1 were biomimetically synthesized.Bioactivity screening experiments showed that compounds(±)-1-12-(±)-1-17,1-18 and 1-19 could inhibit the growth of A549 tumor cells.Nine compounds(2-1-2-9)were isolated and identified from Onchidium sp.collected from Weizhou Island,South China Sea.Only one of them is a new compound.The relative and absolute configurations of the new compound 2-1 were determined by X-ray diffraction analysis and TDDFT-ECD calculation.In bioassays,compound 2-3-2-6 showed cytotoxic activity against A549,SUN-398,Capan-1 and HT-29 tumor cells.The chemical investigation of Lobophytum sp.collected off the Xisha Island in the South China Sea had led to the discovery of 31 compounds(3-1-3-31),including 10 new compounds.The relative configurations of new compounds 3-1 and 3-2 were determined by QM-NMR method.The reliability of QM-NMR method was verified by the X-ray diffraction analysis using Cu/Ga Kα radiation.Then,the relative configurations of compounds 3-3-3-10 were also determined by QM-NMR method.The absolute configurations of new compounds were determined by the application of the modified Mosher’s method,the X-ray diffraction analysis using Cu/Ga Ka radiation,and chemical transformation.Compounds 3-1-3-10 exhibited cytotoxicity in in vitro bioassays against HT-29,Capan-1,A549,and SNU-398 human cancer cell lines.The chemical investigation of Litophyton setonesis collected from the Bali Sea had led to the discovery of 16 compounds(4-1-4-16),including 5 new compounds.Nine compounds(4-9a-4-9g,4-5a and 4-5b)were derived from compounds 4-5 and 4-9.Among them,new compounds 4-5a and 4-5b have a novel type of diterpene carbon skeleton with an uncommon spiral[4,5]decane ring system,which were formed by the breaking of cyclopropane in the acid hydrolysis of compound 4-5.The relative configurations of the new compounds 4-1-4-5 were determined by QM-NMR calculation.In in vitro bioassays,compounds 4-1-4-9 exhibited cytotoxicity against A549,SNU-398,Capan-1,and HT-29 human cancer cell lines.