Studies On Secondary Metabolites And Their Biological Activity Of Three Medicinal Plants

Thiophene acetylenes are widely distributed in the Compositae, which have cytotoxic activities, antibacterial activities, phototoxic and photoactivated insecticidal activity, while alkaloids, possessing complex multi-ring skeleton, produce easily novel skeleton structures. They act an important role in the development of new drugs. In search for structurally unique and biogenetically interesting from these medicinal plants, the secondary metabolites and their biological activities from two Compositae plants (Xanthopappus subacaulis C. Winki and Senecio chrysanthemoides) and one plant rich in alkaloids(Alstonia scholaris) were systematically studied in this dissertation.Ninety-eight compounds were isolated from the three medicinal plants by using conventional extraction, liquid-liquid extraction, silica gel and RP C18column chromatography, preparative thin layer chromatography, Sephadex LH-20column chromatography gel, macroporous resins gel column chromatography, MCI gel column chromatography, HPLC. The structures of these compounds were determined on the basis of IR, UV, EIMS, ESIMS and HRESIMS,1D-NMR and2D-NMR, and their absolute configurations were deduced using the CD exciton chirality method and single-crystal X-ray diffraction.Fifty-five compounds were isolated from X. subacaulis, including ten thiophene acetylenes (six new compounds) and five furanosesquiterpenes (two new compounds), together with flavonoids, diterpenoids, triterpenoids, ionones and their analogues, steroids, lignans and coumarins. The isolated thiophene acetylenes and furanosesquiterpenes were tested for their antibacterial activity against five bacteria. The isolated thiophene acetylenes and furanosesquiterpenes were tested for their antibacterial activity against five bacteria. Compound Xs1with threo configuration exhibited the strong activity against Bacillus subtilis with minimum inhibitory concentration (MIC) of7.25μg/mL, whereas compound Xs2with erythro configuration possessed broad-spectrum antibacterial activity against, respectively. Meanwhile, compounds Xs3, Xs4, Xs7and Xs8substituted with a C1atom at C-14showed moderate inhibitory activity against E. coli, B.cereus, S. aureus, E. carotovora and B. subtilis with MICs ranging from31.25to62.5μg/mL. The biosynthetic pathway of thiophene acetylenes was proposed.Twenty-five compounds were isolated from S. chrysanthemoides, including three new simple single-ring compounds, six known pyrrolizidine alkaloids and five sesquiterpenes and so on.Eighteen indole alkaloids were isolated from A. scholaris, including one novel alkaloid,17-nor-excelsinidine (As1) possessing an unusual1-azoniatricyclo [4.3.3.0] undecane moiety. The structure and absolute stereochemistry of As1were rigorously determined by a combination of NMR spectroscopy and X-ray crystallography. Biogenetic schemes originating from an akuammigine-type indole alkaloid strictamine (As16) are presented to rationalize the structure of compound1, the isolated alkaloids As1-16showed significant inhibition against herpes simplex virus (HSV) and adenovirus (ADV), the SI values ranges from4.67to17.77, the anti-HSV and the anti-adenovirus activities of compounds As1-16were comparable or higher than that of acyclovir (ACV) based on the values of EC50.The distribution and biological activity of the thiophene derivatives in Compositae plants are reviewed. Compositae plants are known to be a rich source of natural thiophene derivatives, and most of them are characteristic of novel structure and possess diverse biological activities.