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Preparation of cyclic derivatives of amino acids using a combination of organocatalysis and metal catalysis
Měrka, Pavel ; Veselý, Jan (advisor) ; Rýček, Lukáš (referee)
This diploma thesis is focused on the combination of enantioselective organocatalysis and transition metal catalysis. In the experimental part of the work, the optimization of reaction conditions with respect to the reaction yields, enantioselectivity and diastereoselectivity was solved. The applicability of the reaction was verified on various substrates. The second part of the work is focused on the study of the mechanism of the reaction using the methods of quantum chemistry. The kinetics of the reaction were monitored by NMR spectroscopy and the mechanism of the reaction was investigated by quantum chemistry methods. Keywords: aminocatalysis, palladium, synergistic catalysis, reaction mechanism, DFT
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Enantioselective synthesis of bispirocyclic compounds
Nigríni, Martin ; Veselý, Jan (advisor) ; Rýček, Lukáš (referee)
This diploma thesis is focused on synthesis of enantiomeric and diastereomeric pure bispirocyclic compounds via sequential Mannich/hydroamination reaction. The first part is focused on the optimization of reaction conditions of enantioselective asymmetric organocatalytic Mannich reaction of pyrazolone derivatives with isatin-derived ketimines. The enantiomerically enriched Mannich adducts were used in hydroamination cyclization. The second part of the work is focused on finding the suitable reaction conditions for performing the Mannich reaction and hydroamination as a sequential reaction leading to bispirocyclic compounds. The application of sequential reaction and selected transformations of bispirocyclic compounds was also performed. Key words Asymmetric synthesis, organocatalysis, Mannich reaction, hydroamination, sequential reaction, bispirocyclic coumpounds.
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Synthesis of azaindenofluorenes
Zelina, Ondřej ; Kotora, Martin (advisor) ; Rýček, Lukáš (referee)
Azafluorene derivates are naturally occurring compounds that possess multiple types of biological activity with the potential of being used as pharmaceuticals. Azaindenofluorenes are studied as potential candidates to be used as organic light-emitting diodes because of their photophysical properties. In this work, compounds belonging to these groups were synthesized using cyclotrimerization. Keywords: cyclotrimerization, catalysis, azafluorene, azafluorenone, azaindenofluorene, azaindenofluorenone, natural compound, OLED
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Design and Synthesis of Prodrugs of 6-Diazo-5-oxo-L-norleucine; Potential Treatment for Glioblastoma
Novotná, Kateřina ; Majer, Pavel (advisor) ; Rýček, Lukáš (referee)
6-Diazo-5-oxo-L-norleucine (DON, 1) is a non-standard amino acid with proven antitumor activity found in soil bacteria of the genus Streptomyces. However, due to the considerable systemic toxicity manifested mainly in the gastrointestinal tract, DON alone is not a suitable clinical candidate for the treatment of cancer. One of the ways to solve the problem of its toxicity is the reversible structural modification of this molecule by protecting both its amino group and carboxyl functional group, by preparing the so-called prodrug of DON. The prepared prodrug may suitably alter the distribution of DON in the body and at the same time increase its permeability to brain tissue. Due to this structural modification, its side effects can be eliminated and a substance for the treatment of brain tumors, such as glioblastoma multiforme (GBM), can potentially be formed. In my dissertation, five strategies for the specific delivery of DON to the brain using different types of its prodrugs are discussed. The new prodrugs are designed to be either capable of spontaneous penetration across the blood-brain barrier or of being a substrate for one of its influx transporters. At the same time, these prodrugs should be stable in other metabolically active organs and blood plasma in order to sufficiently reduce the...
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