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Preparation of 3-phenylpentanoic and 3-phenylpent-2-enoic acid derivatives
Fatka, David ; Machara, Aleš (advisor) ; Veselý, Jan (referee)
This Bachelor's thesis deals with preparation of the intermediates of the analgesic tapentadol. The chosen synthetic strategy requires a preparation of appropriate derivatives of 3-phenylpentanoic and 3-phenylpent-2-enoic acid. Synthesis of those derivatives represents the cornerstone of the thesis. In the first part, the thesis describes an effort associated with a preparation of 1-[(3-benzyloxy)phenyl]propan-1-one, a necessary intermediate for the preparation of the titled compounds. Then addition reactions were studied on the aforementioned ketone. The second part of the thesis focuses on one particular addition, a Reformatsky reaction, and deals with further optimization. In addition, the submitted thesis also describes variety of attempts to carry out dehydration of the Reformatsky adducts, namely, benzylic tertiary alcohols. Powered by TCPDF (www.tcpdf.org)
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Synthesis and properties of complex π-electron systems with helical chirality
Houska, Václav ; Stará, Irena (advisor) ; Machara, Aleš (referee)
Planar shape-persistent macrocycles have been known for a long time and are routinely synthesized today. Non-planar 3D structures, however, still remain challenging synthetic targets in many cases. The objective of this Thesis was to develop a synthetic route to shape-persistent macrocycles containing dibenzo[5]helicene or its derivatives as structural units employing alkene and alkyne metathesis. The Introduction focuses on various methods of the macrocycle synthesis, on alkyne metathesis, and synthesis of helicenes is shortly reviewed as well. Then, the first part of Results and discussion describes the synthesis of 3,16-dichlorodibenzo[5]helicene and its derivatives. In the second part, the macrocycle synthesis from these dibenzohelicenes is discussed. The Experimental part provides a detailed description of performed experiments along with characterization of all new compounds prepared.
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Cycloaddition of 3-(deoxyribos-1-yl)propynoate with alkynes
Kulhavá, Lucie ; Kotora, Martin (advisor) ; Machara, Aleš (referee)
The object of this work is development of method for a syntesis of Dewar benzenes bearing the deoxyriboside group. The synthesis was based on ethynylation of halogenose resulting in the formation of a mixture of anomeric ethynyldeoxiriboses, which was followed by silylation and separation of individiual anomers. After removal of the silyl group the isomerically pure ethynyldeoxyriboses were transformed into corresponding propynoates that were the key substance for the formation od Dewar benzenes. The reaction of the propynoates with the tetramethylcyclobutadiene-aluminium trichloride complex provided the desired Dewar benzenes bearing the deoxyribose group. Finally, rearrangement of the formed Dewar benzenes to 1-aryldeoxyriboses was studied under thermal and photochemical conditions. Keywords: cycloaddition, arenes, Dewar benzene
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Development of new methods for the synthesis of compounds containing the pyridine ring
Frejka, David ; Kotora, Martin (advisor) ; Machara, Aleš (referee)
Tato diplomová práce se zabývá novými reakcemi v oblasti katalytických aktivací C-C vazeb v substrátech obsahující pnuté kruhy a jejich následné funkcionalizace při reakcích s trojnou vazbou alkynů vedoucí k rychlé a jednoduché přípravě regioselektivně substituovaných polyaromatických derivátů. V rámci této práce byly vyvinuty vůbec první postupy umožňující selektivní aktivace C-C vazeb v nesymetricky substituovaných systémech (1-azabifenylenech) vůči pnutému kruhu a jejich reakce se substituovanými alkyny na principu cyklotrimerizace. Místo inserce alkynu může být ovlivněno použitím některých katalytických systémů obsahující iridiové a rhodiové komplexy (schéma 1). Tento postup umožňuje jednoduchou, přímočarou a efektivní přípravu derivátů benzochinolinových skeletů, které jsou hojně využívány v mnoha oblastech chemie. Schéma 1 Regioselektivní aktivace C-C vazeb v 1-azabifenylenech Klíčová slova: aktivace C-C vazeb, 1-azabifenylen, cyklotrimerizace, inserce
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Synthesis of peptidic inhibitors targeting PA-PB1 interface of influenza RNA polymerase
Palacková, Miroslava ; Machara, Aleš (advisor) ; Veselý, Jan (referee)
The submitted Thesis deals with preparation of a hexapeptides inhibiting protein-protein interaction of PA-PB1 subunits of influenza RNA polymerase. Crucial part of the Thesis represent modifications of particular small hexapeptide at its two "hot spots". It means at positions that significantly contribute to the binding of both subunits. These modifications resulted in preparation of two series of distinct hexapeptides. With regards to the fact that one designed hexapeptide contains unnatural and commercially unavailable amino acids this amino acid had to be prepared from simple building blocks. Apart from aforementioned work the Thesis also covers effort to prepared bicyclic peptide that contains sequences of peptidic inhibitor of protein-protein interactions and also cell-penetration peptide. Key words: synthesis, peptides, inhibitors, influenza, polymerase
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Synthesis of Neuraminidase binders suitable for theranostics
Berenguer Albiñana, Carlos ; Machara, Aleš (advisor) ; Cibulka, Radek (referee) ; Soural, Miroslav (referee)
Influenza viruses cause respiratory illnesses which can vary in severity depending on the strain of the virus, as well as the age and health condition of the host. Influenza remains a major threat to public health due to its nature prone to suffer mutations. As a result, vaccines have to be reformulated annually and new strains may cause sporadic global pandemics. Furthermore, the recent emergence of resistant strains of the virus against the current standard of care (oseltamivir and zanamivir) underlines the need of novel anti-influenza therapeutics. The aim of this dissertation work is to contribute to the discovery of new anti-influenza inhibitors either by rational drug-design and optimization of oseltamivir structure, or by developing screening assays suitable for the discovery of novel inhibitors of the enzymes neuraminidase or RNA-polymerase. Scheme 1. Overview of the strategy used for the development of new anti-influenza therapeutics. The dashed arrows indicate the inhibitors that were converted into probes and their corresponding target enzymes Two main modification points were explored for the improvement of oseltamivir properties (Scheme 1); modifications at carbon C-3 aimed to overcome oseltamivir resistance caused by common mutations like H274Y, meanwhile modifications at carbon C-5...
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