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001037852 005__ 20250131215339.0
001037852 020__ $$a978-3-95806-801-8
001037852 037__ $$aFZJ-2025-00995
001037852 1001_ $$0P:(DE-Juel1)180402$$aKlischan, Moritz$$b0$$eCorresponding author
001037852 245__ $$aBiaryl-based natural products as structural motif for pharmaceutically relevant compounds$$f - 2024-09-27
001037852 260__ $$aJülich$$bForschungszentrum Jülich GmbH Zentralbibliothek, Verlag$$c2025
001037852 300__ $$aV, 657
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001037852 3367_ $$0PUB:(DE-HGF)11$$2PUB:(DE-HGF)$$aDissertation / PhD Thesis$$bphd$$mphd$$s1738342615_1097
001037852 3367_ $$2DRIVER$$adoctoralThesis
001037852 4900_ $$aBioorganische Chemie an der Heinrich-Heine-Universität im Forschungszentrum Jülich$$v49
001037852 502__ $$aDissertation, Düsseldorf, 2024$$bDissertation$$cDüsseldorf$$d2024
001037852 520__ $$aBiaryls are important structural motifs for both pharmaceutically relevant compounds as well as ligands, and catalysts in chemical transformations. With the aim of contributing to the everexpanding methodology towards biaryls, different synthesis strategies were devised and implemented to obtain synthetically relevant biaryls. Moreover, stereoselective palladium catalyzed transformations were investigated for the synthesis of bicyclic compounds. 8,8′′-Biflavones, a class of biaryl-based natural products, were investigated for their bioactivity against various human pathogens. A synthesis route for the construction of highly functionalized racemic biaryl building blocks in three steps was established in a scalable fashion. Enabled by this method, the first extensive library of 8,8′′-biflavone analogues was synthesized. This dedicated library was then evaluated regarding its pharmaceutical potential in cooperation with M.Sc. Lena Berning and M.Sc. Flaminia Mazzone (Heinrich Heine University Düsseldorf). In addition to promising results for these biflavones, bichalcones obtained as key intermediates were identified as novel drug scaffolds. Based on these first hits, further amino-8,8′′-biflavones including the first non-C2-symmetrical 8,8′′-biflavone were synthesized. In cooperation with M.Sc. Céline David (Heinrich Heine University Düsseldorf) the structure activity relationship was probed, and bioactivities obtained. Next a strategy involving cyclic diaryliodonium salts towards an enantiopure building block was implemented. Extensive investigations were undertaken, and ultimately a scalable protocol successfully established. These prochiral building blocks were then applied to construct enantiopure dimeric flavonoids and thus the usefulness of the established methodology shown. In addition to these investigations, palladium-catalyzed methods were investigated to overcome advanced synthetic challenges. For one, the Catellani reaction was used to obtain biaryls inaccessible by state-of-the-art methods. Factors critical for this transformation were identified, and a protocol for the synthesis of tri-ortho-substituted biaryls established. Moreover, first investigations into stereodynamic biaryl-based palladacycles were conducted. The proposed stereodynamics of these palladium complexes were supported by preliminary computational calculations (DFT). Finally, in collaboration with the working group of Prof. Mark Lautens (University of Toronto), the use of chiral oxabicycles as acetylene analogues was thoroughly investigated. A mechanism to explain the observed stereoselectivity of the reaction was proposed and supported by experimental findings. Finally, DFT calculations were conducted to rationalize the observed selectivities.
001037852 536__ $$0G:(DE-HGF)POF4-2171$$a2171 - Biological and environmental resources for sustainable use (POF4-217)$$cPOF4-217$$fPOF IV$$x0
001037852 536__ $$0G:(DE-Juel1)GRK-2158-20170406$$aGRK 2158 - Graduiertenkolleg 2158 – Naturstoffe und Analoga gegen Therapie-resistente Tumoren und Mikroorganismen: Neue Leitstrukturen und Wirkmechanismen (GRK-2158-20170406)$$cGRK-2158-20170406$$x1
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001037852 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)180402$$a Heinrich-Heine-Universität Düsseldorf$$b0
001037852 9131_ $$0G:(DE-HGF)POF4-217$$1G:(DE-HGF)POF4-210$$2G:(DE-HGF)POF4-200$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-2171$$aDE-HGF$$bForschungsbereich Erde und Umwelt$$lErde im Wandel – Unsere Zukunft nachhaltig gestalten$$vFür eine nachhaltige Bio-Ökonomie – von Ressourcen zu Produkten$$x0
001037852 9141_ $$y2025
001037852 920__ $$lyes
001037852 9201_ $$0I:(DE-Juel1)IBOC-20090406$$kIBOC$$lInstitut für Bioorganische Chemie (HHUD)$$x0
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