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Fluorescently labeled ligands for the Mu-opioid receptors
Hadzima, Martin ; Machara, Aleš (advisor) ; Kohout, Michal (referee)
This Bachelor's thesis deals with preparation of fluorescently labeled opiates, which allow detection of µ-opioid receptors and study of their interaction with ligands, using fluorescent techniques. As substrates designated for chemical modifications were chosen semi-synthetic opiates, naloxone and naltrexone. Their conversion to corresponding C-6 hydrazones allowed further modifications of these substances and tracking, if any changes to their ability to interact with µ-opioid receptors ocurr. Firstly, known adducts of these hydrazones with fluorescein isothiocyanate were prepared. Then, we inserted linkers of different lengths between the opiate fragment and the fluorescent tag, systematically. Mentioned linkers were prepared from tetraethyleneglycole derivatives with aim to study binding constants of modified µ-opioid receptor ligands. In the end, we decided to prepare opiate conjugate with particular linkers of length corresponding, approximately, to decaethyleneglycole. Two different procedures were proposed for the preparation of this linker. One of them used click chemistry concept and the other was based on classic amide coupling. Both conjugates were converted to adducts with fluorescein to verify their specific binding to µ-opioid receptors. They were also provided to co-operating group,...
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Preparation of bifunctional organocatalysts
Rohaľová, Dominika ; Veselý, Jan (advisor) ; Trnka, Tomáš (referee)
This bachelor thesis deals with the synthesis of bifunctional thiourea catalysts and corresponding building blocks derived from levoglukosane. The first part was of this thesis is focused on the preparation 1,6:2,3-dianhydro-4-azido-4-deoxy-β-D-mannose. The second part of the thesis is deals with the preparation od bifunctional catalyst. Keywords Asymmetric synthesis, organocatalysis, saccharides, bifunctional calatysts, thiourea, morpholine.
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Study of molecular organization of cytochrome P450 system using photoactivatable proteins
Dědič, Jan ; Hodek, Petr (advisor) ; Novák, Petr (referee)
The cytochrome P450 system plays an important role in metabolism of endogenous compounds and xenobiotics. This system consists of cytochrome P450, NADPH:cytochrome P450 oxidoreductase (CPR), cytochrome b5 and NADH:cytochrome b5 reductase (CYB5R3). Explanation of protein-protein interactions among these reaction partners is essential for understanding the function of the entire system. Covalent cross-linking is a favorable method for studying these interactions. In this work a photo-activatable analogue of amino acid L-methionine (L-photo-methionine) was used as a cross-linking agent. This work is focused on the organic synthesis of L-photo-methionine, expression and isolation of CPR and CYB5R3 as photoactivable proteins containing incorporated L-photo-methionine. Auxotrophic strain of E.coli B834 (DE3) and minimal media were used for the expression. CYB5R3 with incorporated L-photo-methionine was successfully expressed and isolated. The extent of L-photo-methionine incorporation was verified by mass spectrometry. Furthermore, the photo-initiated cross-linking of CYB5R3 with cytochrome b5 was tested. Key words: photolabile amino acid, protein expression, synthesis
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Stereoselective synthesis of spiro compounds containing cyclohexenecarboxylic acid
Dočekal, Vojtěch ; Veselý, Jan (advisor) ; Matoušová, Eliška (referee)
This bachelor thesis is focused on stereoselective preparation of spiro compounds using organocatalytic approach and their transformation to substrates with potential biological activity. First part of this work deals with stereoselective synthesis of spiro compounds using heterocyclic enals and sulphur-containing nucleophile. These organocatalytic reactions were catalysed by chiral secondary amine utilizing tandem Michael/Michael/aldol reaction. Second part of this work is focused on transformation of prepared unsaturated heterocyclic spiro aldehydes to corresponding carboxylic acids, which will be studied for their possible biological activity. Key words Enantiomer, diastreomer, stereoselective synthesis, organocatalysis, Michael addition, aldol condensation, Wittig reaction, Pinnick oxidation.
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Synthesis and catalytic properties of phosphinoferrocene guanidine
Bárta, Ondřej ; Štěpnička, Petr (advisor) ; Vojtíšek, Pavel (referee)
Title: Synthesis and catalytic properties of phosphinoferrocene guanidine Author: Ondřej Bárta Institution: Faculty of Science, Charles University in Prague, Department of Inorganic Chemistry Supervisor: prof. RNDr. Petr Štěpnička, Ph.D. Polar phosphine ligands proved to be useful in homogeneous and biphasic catalysis. Most of these phosphines bears anionic functional groups. On the other hand, functionalization of phosphines by cationic substituents is still quite uncommon, although these functional groups possess properties that could improve catalytic performance of the catalyst. In this regard, nitrogenous bases are particularly attractive due to their inherent basicity and the ability to enter into hydrogen bonding interactions. This thesis describes the synthesis of a novel ferrocene-based phosphine functionalized with guanidine moiety, viz. N-[1′-(diphenylphosphino)ferrocenylmethyl]guanidine (3). This compound was obtained by direct guanylation of 1′-(diphenylphosphino)- 1-(aminomethyl)ferrocene (2) (see scheme). Compound 3 was further used to prepare palladium complexes including the unusual zwitterionic complex [PdCl3(3H)]. The molecular structures of the prepared complexes were determined by X-ray diffraction analysis. Catalytic properties of phosphine 3 and complex [PdCl3(3H)] were...
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Comparison Philosophies of Jan Amos Komenský and René Descartes
Dobrovodská, Helena ; Hogenová, Anna (advisor) ; Rybák, David (referee)
Comparison of Philosophies of Jan Ámos Komenský and René Descartes The aim of this work is comparison of philosophies of Jan Ámos Komenský and René Descartes based on their essential works, i.e."Labyrint světa a ráj srdce" (The Labyrinth of the World and the Paradise of the Heart) and "Úvahy o první filozofii" (Meditations on First Philosophy), in which God's existence and the difference between the human soul and body are proved. The philosophy of both contemporaries originated in the 17th century on the background of the Thirty Years' War and the Counter-Reformation. The rationalism of René Descartes, which starts Cartesian thinking, seems to be substantially different from the philosophy of Komenský based on Neoplatonism and Christianity. In the thought of Descartes analysis, mathematical operationalism, is principal, whereas Komenský synthesizes and puts the whole together. The first chapter of the thesis deals with the lives, period and works of Komenský and Descartes. It is possible to find significant similarities in their life stories. The second chapter deals with the interpretation of "The Labyrint of the World and the Paradise of the Heart" and the interpretation of "Meditations of First Philosophy", in which God's existence and the difference between the human soul and body are proved....
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Deposited palladium catalysts
Semler, Miloslav ; Štěpnička, Petr (advisor) ; Balcar, Hynek (referee) ; Bulánek, Roman (referee)
Palladium catalysts are frequently used in C-C coupling reactions. The aim of this work is to prepare several heterogeneous palladium catalysts from comercially available silica gel, each with different bifunctional ligand deposited on the surface of silica gel by N-propylamide linking group, and their testing on several C-C coupling reactions (Heck reaction, reaction of acyl chlorides with boronic acids and reaction of acyl chlorides with terminal acetylenes). Some other aspects of heterogeneous catalysis (such as palladium leaching into the reaction mixture and possibility of catalyst reuse) are discussed, too. Powered by TCPDF (www.tcpdf.org)
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Synthesis of antimicrobial compounds based on derivatives of salicylic acid
Tvrdý, Václav ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Schiff bases are widely used both in technical practice and in the field of medicine. For their antimicrobial activities are studied as potential antimacterial and abtifungal drugs. With increasing level of resistence to currently drugs is the development of new substances very intense. Salicylanilides are a group of substances with antimicrobial activity and are also intensively studied. Based on that we were synthesized novel Schiff bases resulting from salicylic acid, respectively salicylanilides. It was concretely prepared five compounds: 5- chloro-N-{4-[phenyl(phenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-bromo-N-{4-[ phenyl(phenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-chloro-N-{4-[phenyl(3- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-chloro-N-{4-[phenyl(4- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-bromo-N-{4-[phenyl(4- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide. The reaction proceeded at the boiling point of the solvent, with catalytic amount of p-toluensulfonic acid. Most of the compounds were characterized by IR, H1 NMR, C13 NMR and melting point. The prepared compounds showed E/Z isomers on double bond, it is demonstrated on NMR specters.
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