Studies On Chemical Constituents And Bioactivities Of Secondary Metabolites From Four Medicinal Plants

This paper consists of six chapters. The first chapter summarized the recent research progress of several dimeric natural compounds. The following four chapters respectively expounded the bioactivities and chemical constituents from four medicinal plants, including Sinomenium acutum (Thunb.) Rehd. Et Wils., Evodia rutaecarpa (Juss.) Benth., Onosma paniculatum Bur. & Franch, and Euphorbia neriifolia Linn. The last chapter was the summarization of this thesis and perspectives of the research topic.By chromatography, spectroscopy technique, X-Ray diffraction experiments, and computational chemistry methods,110 compounds were isolated and identified from above-mentioned four medicinal plants, including 23 new compounds. The compounds included alkaloids, quinones, diterpenoids, lignans and other types of compounds, and the new ones mainly belongs to alkaloids, quinones and diterpenoids. The novel bistetrahydroisoquinoline alkaloids, two morphinane-proaporphine ones and a morphinane-benzylisoquinoline alkaloid, were first discovered from Sinomenium acutum. The biological activities, including cytotoxic activity, anti-inflammatory activity, and anti-HIV activity of the isolates, were evaluated, and some of them exhibited moderate biological activities.The dried rhizomes of Sinomenium acutum is usually used as a Chinese folk medicinal herb for the treatment of rheumatoid arthritis.34 compounds, including 6 new ones, were isolated and identified from the rhizomes of S. acutumt. Sallisonines A-C (1-3) were unprecedented bistetrahydroisoquinoline alkaloids with morphinane-proaporphine and morphinane-benzylisoquinoline skeletons. Sallisonine D (4) was the new tetrahydroisoquinoline alkaloid ketones, sallisonine E (5) was an oxoisoaporphine-type alkaloid, and compound 6 was a hasubanane glucoside similar to the morphinane type. Sallisonine A (1) exhibited cytotoxic activity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines in vitro, and the inhibition (IC50=18.45 μM) for A-549 cell was greater than dimeric morphinane alkaloids (IC50=65.5～71.8 μM). Sallisonine B (2) showed moderate ability to inhibit NO production of LPS-stimulated RAW264.7 macrophages, with IC50 of 14.79 μM. In addition, a possible biogenetic pathway of the morphinane-proaporphine bistetrahydro- isoquinoline alkaloid was also proposed, and the possiblity of natural existence of the metabolites base on the metabolism pathways of plant itself was described.Evodia rutaecarpa has abundant of indole and quinolone alkaloids. Our investigation of the plant led to the isolation of 33 compounds, including four new ones. Evodiakine (1) with 6/5/5/7/6 ring system was found at first as a rutecarpine-type alkaloid, and its structure was elucidated as an enantiomer by spectral analysis and single-crystal X-ray diffraction study. It was successfully isolated as (-)-isomer and (+)-isomer by using chiral column chromatography technology, and the absolute configuration of 1 was determined by computational chemistry. Evollionines A (2) and B (3) were evocarpine-type alkaloids with the structure characteristic of 4,21-seco-2 or 2,3-seco-3, and evollionine C (4) was a new quinolone alkaloid. On anti-inflammatory activity test, the racemate showed weak inhibition of NO production in vitro compared with (-)-isomer and (+)-isomer.The nineteen compounds were isolated from Onosma paniculatum, including 5 new compounds. Among them, compound 1 was a new shikonin dim eric derivative. Compounds 2-4 were new dihydrobenzofuran quinones with a furan ring at C-5 and C-12 by-O-bond, which fused on the naphthoquinone benzene ring. Compound 5 was a benzohydroquinone whose C-2 and C-3 were substituted by a ten-membered macrocyclic monoterpene. Naphthoquinones strongly exhibited cytotoxic activity in vitro. Lithospermum dimers did not show obvious cytotoxicity and anti-inflammatory effects.From the 75% acetone extracts of Euphorbia neriifolia, the 24 compounds were isolated and identified, and eight were new compounds. Euphornerine (1) was found at first from this genus as a new compound containing three N-atoms. New compounds, euphorneroids A-C (2-4), were new eleven-membered macrocyclic ingol-type diterpenoids. However, euphorneroids D-G (5-8) were ent-atisine type diterpenoids, of which euphorneroid D (5) belongs to seco-type compound, and the strcture of euphorneroid G (8) containing a dioxolane structure. Anti-HIV experimental results showed that the dioxolane partial structure might be an active unit. The triterpenoid-contained fraction had a higher anti-HIV activity than the diterpenoid-contained fraction, which indicating that triterpenoids may play a role on anti-HIV effect of E. neriifolia.