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Herein described is the discovery of three novel types of dimeric naphthylisoquinoline alkaloids, named mbandakamines, cyclombandakamines, and spirombandakamines. They were found in the leaves of a botanically as yet unidentified, potentially new Ancistrocladus species, collected in the rainforest of the Democratic Republic of the Congo (DRC). Mbandakamines showed an exceptional 6′,1′′-coupling, in the peri-position neighboring one of the outer axes, leading to an extremely high steric hindrance at the central axis, and to U-turn-like molecular shape, which – different from all other dimeric NIQs, whose basic structures are all quite linear – brings three of the four bicyclic ring systems in close proximity to each other. This created an unprecedented follow-up chemistry, involving ring closure reactions, leading to two further, structurally even more intriguing subclasses, the cyclo- and the spirombandakamines, displaying eight stereogenic elements (the highest total number ever found in naphthylisoquinoline alkaloids). The metabolites exhibited pronounced antiplasmodial and antitrypanosomal activities. Likewise reported in this doctoral thesis are the isolation and structural elucidation of naphthylisoquinoline alkaloids from two further potentially new Ancistrocladus species from DRC. Some of these metabolites have shown pronounced antiausterity activities against human pancreatic cancer PANC-1 cells.
The indepth metabolic profiling of the crude extracts of two African Ancistrocladus species viz. A. likoko from Central Africa and A. abbreviatus from West Africa, resulted in a total of 87 alkaloids among them 54 new ones. All of the compounds were intensely elucidated by 1D and 2D NMR, HRESIMS, as well as chemical and chiroptical techniques.
Among the newly discovered compounds are quinoid naphthylisoquinolines with an ortho-diketone in the naphthalene portion, nor-naphthylisoquinoline alkaloid lacking the always present methyl group at C-1, seco-(ring cleaved) naphthylisoquinolines, and a newly discovered class of natural products called the naphthylisoindolinones.
Some of the compounds displayed strong antitumoral activities against human pancreatic cancer cells and leukemia cells in-vitro.
Nowadays, the management of infectious diseases is especially threatened by the rapid emergence of drug resistance. It has been suggested that the medicine quality assurance combined with good medication adherence may help to reduce this impendence. Moreover, the search for new antimicrobial agents from medicinal plants is strongly encouraged for the exploration of alternatives to existing therapies. In this context, the present work focused on both the quality evaluation of commercialized antimalarial medicines from the Democratic Republic of the Congo and on the phytochemical investigations of a Congolese Ancistrocladus species.
Die Produktion von Abwehr-, Signal- und Botenstoffen sichert vielen Pflanzen und Mikroorganismen das Überleben in einer sich ständig wandelnden Umwelt mit zahlreichen Konkurrenten und Feinden. Diese Sekundärmetabolite können oft medikamentös gegen Pathogene eingesetzt werden, die den Menschen befallen und Krankheiten verursachen. Die Herausforderung besteht dabei in der selektiven und sensitiven Detektion, der schonenden Isolierung und der richtigen und kompletten Strukturaufklärung dieser Moleküle, sowie der eventuellen synthetischen Modifikation, um eine bessere Verträglichkeit oder Wirkung für den menschlichen Körper zu erreichen. Leistungsfähige chromatographische Instrumente zur Trennung wie HPLC und CZE, emfindliche Detektoren wie UV- und Massenspektrometer, sowie aussagekräftige Messverfahren zur Charakterisierung struktureller Merkmale wie NMR- und CD-Spektroskopie und quantenchemische Rechnungen sind dabei von essentieller Bedeutung.
Mit diesen – und weiteren – Methoden gelang in der vorliegenden Arbeit die Detektion, Isolierung und Strukturaufklärung neuer Naphthylisochinolin-Alkaloide aus zwei tropischen Ancistrocladus-Lianen, die Charakterisierung von bekannten und neuen Polyketiden aus einem Pilz der Gattung Streptomyces, sowie die Analyse von Glucosinolaten im Phloemsaft der Modellpflanze Arabidopsis thaliana.
Herein described are the isolation, structural elucidation, and biological evaluation of highly thrilling monomeric and dimeric new naphthylisoquinoline alkaloids from A. ealaensis. The separation, chiral resolution, and characterization of a series of stereoisomeric 2,3-dihydrobenzofuran neolignans are also reported. The analytical and phytochemical analysis on two Congolese antimalarial herbal drugs is part of the last chapter of the results. In this last case, major concerns on widely used Congolese herbal drugs are discussed.