@phdthesis{Faber2007,
  author    = {Faber, Johan Henrik},
  title     = {Naphthylisoquinoline Alkaloids : Structural Elucidation, Metabolism and Functional Analysis of their Bioactivities},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22789},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {This thesis deals with the isolation and structural elucidation of bioactive naphthylisoquinoline alkaloids and related analogs. The mode of action of the antiplasmodial activity exhibited by the naphthylisoquinoline alkaloids was explored and compared to that of the antimalarial drug chloroquine. Furthermore, the phase 1 and 2 metabolism of dioncophyllines A and C and dioncopeltine A were investigated. In detail the following results have been obtained: • From the leaves of the recently discovered East African liana A. tanzaniensis six naphthylisoquinoline alkaloids were isolated. • The leaves of a botanical yet undescribed Ancistrocladus species, collected by Prof. Dr. V. Mudogo in the Democratic Republic of Congo in the habitat Yeteto near the town Ikela, were analyzed for naphthylisoquinoline alkaloids for the first time. The isolation work led to the first identification of an N,C-coupled naphthyldihydroisoquinoline alkaloid; ancistrocladinium B. Phytochemical investigation of the roots of the Congolese Ancistrocladus species (habitat Yeteto), , afforded five new derivatives of known naphthylisoquinoline alkaloids, namely 5'-O-demethylhamatine, 5'-O-demethylhamatinine, 6-O-demethylancistroealaine A, 6,5'-O,O-didemethylancistroealaine A, and 5-epi-6-O-methylancistrobertsonine A, along with six known naphthylisoquinoline alkaloids. • The antiplasmodial activity guided purification of 60Co irradiated samples containing commercially available naphthylisoquinoline related substances, afforded the isolation of the irradiation products 3,4-dihydro-1-isoquinolinone, 3,4-dihydro-1-isoquinolineamine, and 1,2,3,4-tetrahydro-1,2-diazirino-isoquinoline. The compounds were found to be more active than the starting material, although only exhibiting weak antiplasmodial activity against P. falciparum. • The effect on the absorption spectrum of FPIX due to complex formation with the naphthylisoquinoline alkaloids dioncophyllines A and C, dioncopeltine A korupensamine A, and ancistrocladine was examined by a titration study. Job's plot analyses by UV-spectroscopy determined the stoichiometry for the complex formation of FPIX and naphthylisoquinoline alkaloids to be 2:1. Furthermore, the dissociation constants for the complexation with FPIX were determined for each of the naphthylisoquinoline alkaloids investigated. Dioncophylline C and dioncopeltine A were found to possess dissociation constants, which are comparable to the one reported for the antimalarial drug chloroquine. The ability of ESI to transfer noncovalent solution-phase assemblies intact into the gas phase, was conducted on solution mixtures of naphthylisoquinoline alkaloid and FPIX, as well as on mixtures of chloroquine and FPIX. The mass spectrometry analyses revealed several peaks, which corresponded to the complex formation of FPIX to the respective ligands investigated. The most interesting results obtained were the detection of peaks corresponding to the complex formation between a chelated dimer of FPIX and dioncophylline Cand of peaks corresponding to a double protonated tetramer of FPIX - consisting of two chelated \&\#61549;-oxo dimers of FPIX - in complex formation with two molecules of chloroquine. • Two phase 1 metabolism products of dioncophylline A were identified. Coelution in combination with HPLC-MS/MS, NMR, and CD investigations assigned the major metabolic product as 5'-O-demethyldioncophylline A. The minor metabolic product was only present in small amounts, which disabled an unambiguous structural characterization of the compound. However, as deduced from the mass spectrometry analyses and exclusion of a possible metabolic oxidation product by coelution with authentic reference material, the metabolite should possess a 4-hydroxylated isoquinoline portion and is assumed to be represented by structure. Dioncophylline C and dioncopeltine A were found to be stable to phase 1 metabolism reactions caused by rat liver microsomes.},
  subject      = {Naphthylisochinolinalkaloide},
  language  = {en}
}
@phdthesis{Ruedenauer2008,
  author    = {R{\"u}denauer, Stefan},
  title     = {Naphthylisochinolin-Alkaloide : Totalsynthese und Biosyntheseuntersuchungen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27997},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {No abstract available},
  subject      = {Naphthylisochinolinalkaloide},
  language  = {de}
}
@article{MasotaOhlsenSchollmayeretal.2022,
  author    = {Masota, Nelson E. and Ohlsen, Knut and Schollmayer, Curd and Meinel, Lorenz and Holzgrabe, Ulrike},
  title     = {Isolation and characterization of galloylglucoses effective against multidrug-resistant strains of Escherichia coli and Klebsiella pneumoniae},
  series = {Molecules},
  volume    = {27},
  journal   = {Molecules},
  number    = {15},
  issn      = {1420-3049},
  doi       = {10.3390/molecules27155045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286179},
  year      = {2022},
  abstract  = {The search for new antibiotics against multidrug-resistant (MDR), Gram-negative bacteria is crucial with respect to filling the antibiotics development pipeline, which is subject to a critical shortage of novel molecules. Screening of natural products is a promising approach for identifying antimicrobial compounds hosting a higher degree of novelty. Here, we report the isolation and characterization of four galloylglucoses active against different MDR strains of Escherichia coli and Klebsiella pneumoniae. A crude acetone extract was prepared from Paeonia officinalis Linnaeus leaves, and bioautography-guided isolation of active compounds from the extract was performed by liquid-liquid extraction, as well as open column, flash, and preparative chromatographic methods. Isolated active compounds were characterized and elucidated by a combination of spectroscopic and spectrometric techniques. In vitro antimicrobial susceptibility testing was carried out on E. coli and K. pneumoniae using 2 reference strains and 13 strains hosting a wide range of MDR phenotypes. Furthermore, in vivo antibacterial activities were assessed using Galleria mellonella larvae, and compounds 1,2,3,4,6-penta-O-galloyl-β-d-glucose, 3-O-digalloyl-1,2,4,6-tetra-O-galloyl-β-d-glucose, 6-O-digalloyl-1,2,3,4-tetra-O-galloyl-β-d-glucose, and 3,6-bis-O-digalloyl-1,2,4-tri-O-galloyl-β-d-glucose were isolated and characterized. They showed minimum inhibitory concentration (MIC) values in the range of 2-256 µg/mL across tested bacterial strains. These findings have added to the number of known galloylglucoses from P. officinalis and highlight their potential against MDR Gram-negative bacteria.},
  language  = {en}
}
@phdthesis{Knauer2011,
  author    = {Knauer, Michael},
  title     = {Aufkl{\"a}rung der Konstitution und Konfiguration von Sekund{\"a}rmetaboliten und Syntheseprodukten mittels NMR, MS, HPLC, CD und ORD sowie Beitr{\"a}ge zur Totalsynthese bioaktiver axial chiraler Naturstoffe},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70990},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Im Laufe der Evolution entwickelten Pflanzen, Bakterien, Pilze und Tiere eine Vielzahl von Signal-, Boten- und Abwehrstoffen. Diese f{\"u}r die Organismen oft lebensnotwendigen Sekund{\"a}rmetabolite werden von den jeweiligen Produzenten oft sehr effizient und teilweise auch hoch stereoselektiv produziert. Die Effizienz und Selektivit{\"a}t, mit denen diese Stoffe mit den in der Natur zur Verf{\"u}gung stehenden biosynthetischen Mitteln hergestellt werden, ist f{\"u}r Chemiker im Labor, trotz eines breiten Methodenrepertoires, eine große Herausforderung und oft gelingt die Laborsynthese nur {\"u}ber viele Stufen sowie in geringen Ausbeuten und/oder mit schlechten Enantio- oder Diastereoselektivit{\"a}ten. Daher wird in der chemischen Synthese immer wieder die Neuentwicklung und Erweiterung von Methoden vorangetrieben. Neben der Synthese im Labor ist auch die Untersuchung von Biosynthesewegen sowie die Charakterisierung der daf{\"u}r verantwortlichen Enzyme ein interessantes Forschungsgebiet, um von der Natur zu lernen und diese Erkenntnisse f{\"u}r die Entwicklung neuer Synthesestrategien und Methoden zu nutzen. Viele der bislang isolierten Verbindungen zeigen neben den f{\"u}r die produzierenden Organismen wichtigen Wirkungen auch Aktivit{\"a}ten gegen f{\"u}r Menschen gef{\"a}hrliche Krankheitserreger. Daher ist die Isolierung und Strukturaufkl{\"a}rung neuer bioaktiver Naturstoffe als Leitstrukturen f{\"u}r neue Medikamente ein lohnendes Ziel f{\"u}r Wissenschaftler. In den letzten Jahren wurden aber immer h{\"a}ufiger bereits bekannte Verbindungen isoliert. Zur Vermeidung solcher Mehrfachisolierung werden auch die analytischen Methoden zur Identifikation und Strukturaufkl{\"a}rung stetig verbessert Einen wichtigen Stellenwert hat hierbei die Kopplung von Messger{\"a}ten wie z.B. MS oder NMR mit chromatographischen Anlagen wie GC, HPLC oder UPLC eingenommen. Die Kombination von Fl{\"u}ssigchromatographie-Anlagen mit chiroptischen Detektoren wie CD-Spektrometern erlaubt hierbei manchmal sogar die Zuordnung von Absolutkonfigurationen direkt aus dem Rohextrakt. Ziel der vorliegenden Arbeit war einerseits die Anwendung neuer Methoden bei der Entwicklung von Syntheserouten zu axialchiralen Naturstoffen und andererseits die Aufkl{\"a}rung der Konstitution und Konfiguration von Naturstoffen und synthetischen Verbindungen sowie die Untersuchung von Biosyntheseintermediaten.},
  subject      = {Totalsynthese},
  language  = {de}
}
@phdthesis{Noll2006,
  author    = {Noll, Torsten Frank},
  title     = {Aufkl{\"a}rung der Biosynthese und Faltungsmodi aromatischer Polyketide in pflanzlichen Gewebekulturen, Mikroorganismen und Insekten sowie Strukturaufkl{\"a}rung von entsprechenden Biosynthese-Intermediaten mittels HPLC-MS, NMR und CD},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-20187},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Polyketide stellen aufgrund ihrer großen strukturellen Vielfalt nach wie vor Leit- und Wirkstoffe f{\"u}r die Pharma- und Pflanzenschutzforschung in den Industriel{\"a}ndern dar und bilden außerdem eine der wichtigsten Klassen von Naturstoffen (Sekund{\"a}rmetaboliten) {\"u}berhaupt. Besonders die Biosynthese aromatischer Polyketide und die hierbei involvierten Enzyme, die Polyketidsynthasen (PKS), wurden von Biosyntheseforschern als hervorragendes Modellsystem zur Untersuchung von Struktur-Funktions-Beziehungen von Multienzymkomplexen erkannt. F{\"u}r annelierte aromatische Polyketide existiert seit dem Jahr 2001 eine biosynthetische Klassifizierung auf Metabolitebene, das sogenannte Modus-F/S-System, mit dessen Hilfe man zwischen pro- und eukaryotischen Produzenten unterscheiden kann. Die Erforschung der detaillierten Biosynthese von aromatischen Polyketiden ist somit in mehrfacher Hinsicht ein lohnendes Ziel. In der vorliegenden Dissertation sollten die Biosynthese und die Faltungsmodi ausgew{\"a}hlter aromatischer Polyketide einschließlich der Charakterisierung potentieller Vorstufen in verschiedensten biologischen Systemen untersucht werden. Die dabei gewonnenen Resultate sind das Ergebnis interdisziplin{\"a}rer Zusammenarbeit.},
  subject      = {Polyketide},
  language  = {de}
}