Discovery of Secondary Metabolites from Rwandese Medicinal Plants : Isolation, Characterization and Biological Activity

Plants have served as the principal source of medicines in different parts of the world through the ages. Herb-derived medicines have been used as decoctions, infusions, tinctures or single substance drugs. Due to their impressive possibility of diversification, plants have also provided an immense universe of creativity for synthetic chemists, who constantly make useful new molecules inspired by the natural molecular architecture. The goal of this thesis work was to investigate secondary metabolites isolated from selected Rwandese medicinal plants. It focused specifically on the isolation, the characterization and the determination of the biological activity of natural products. The investigated plants belong to the families of Myrtaceae (Eucalyptus melliodora and Eucalyptus anceps), Fabaceae (Eriosema montanum), Lamiaceae (Clerodendrum myricoides) and Asteraceae (Senecio mannii). These were selected from the Rwandese flora based on information collected from traditional healers, and from the literature. The study made use of chromatographic, spectroscopic and spectrometric methods for separation, purification and structure elucidation of the plant constituents. In paper I, the chemical composition and antifungal activity of essential oils of E. melliodora and E. anceps were discussed. The essential oils were composed of mono- and diterpenes, and their alcohol derivatives. The essential oil mixtures exhibited antifungal activity against food spoilage fungi. In paper II, E. montanum was investigated and a total of 20 compounds were isolated including two new prenylated dihydrochalcones and eighteen known secondary metabolites. Their antibacterial activities and cytotoxicity were determined. In paper III, the isolation of three new and two known iridoid glycosides from C. myricoides was reported along with the antiviral activities of the crude extract and of the isolates. In paper IV, the phytochemical investigation of S. mannii was reported. It afforded one new silphiperfolanol angelate ester, two new macrocyclic pyrrolizidine alkaloids, and five known secondary metabolites. Two new synthetic derivatives were obtained by structural modification of 2-angeloyloxy-5,8-dihydroxypresilphiperfolane. The relative stereochemistry of senaetnine was investigated by NAMFIS and confirmed to be 7R, 12R, and 13R. The new compounds isolated in this study have shown biological activities, and may provide lead compounds for drug discovery and technological applications