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@PHDTHESIS{Klischan:1037852,
author = {Klischan, Moritz},
title = {{B}iaryl-based natural products as structural motif for
pharmaceutically relevant compounds},
volume = {49},
school = {Düsseldorf},
type = {Dissertation},
address = {Jülich},
publisher = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
reportid = {FZJ-2025-00995},
isbn = {978-3-95806-801-8},
series = {Bioorganische Chemie an der Heinrich-Heine-Universität im
Forschungszentrum Jülich},
pages = {V, 657},
year = {2025},
note = {Dissertation, Düsseldorf, 2024},
abstract = {Biaryls 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.},
cin = {IBOC},
cid = {I:(DE-Juel1)IBOC-20090406},
pnm = {2171 - Biological and environmental resources for
sustainable use (POF4-217) / GRK 2158 - Graduiertenkolleg
2158 – Naturstoffe und Analoga gegen Therapie-resistente
Tumoren und Mikroorganismen: Neue Leitstrukturen und
Wirkmechanismen (GRK-2158-20170406)},
pid = {G:(DE-HGF)POF4-2171 / G:(DE-Juel1)GRK-2158-20170406},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
url = {https://juser.fz-juelich.de/record/1037852},
}