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Cycloaddition of 3-(deoxyribos-1-yl)propynoate with alkynes
Get PDFThe 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 benzen
Fluorescently labeled ligands for the Mu-opioid receptors
No full textThis 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,..
Amination of pyrazolones
Get PDFDepartment of Organic ChemistryKatedra organické chemiePřírodovědecká fakultaFaculty of Scienc
pi-Konjugované oligomery obsahující helikálně chirální jednotky
No full textV rámci diplomové práce byl výzkum zaměřen na syntézu velkých rigidních makrocyklů obsahujících helikální jednotky. Dřívější syntetické přístupy studované v naší skupině (využívající zejména metathesi alkenů a alkynů) selhaly a bylo proto zapotřebí hledat robustnější syntetickou cestu. Postupná konstrukce acyklického trimeru za použití cross- couplingových reakcí se zdála být vhodným postupem eliminujícím nechtěnou oligomerizaci, jež byla pozorována u syntéz využívajících metathesi. Pro uzavření makrocyklu se jevilo použití intramolekulární McMurryho reakce nebo metathese alkenů jako vhodné řešení. V rámci této práce byla vyvinuta optimalizovaná syntéza solubilizovaného dibenzo[5]helicenu a jeho derivátů, které měly sloužit jako stavební bloky zamýšleného acyklického trimeru. Jak Heckova, tak Suzukiho-Miyaurova reakce vedly ke směsím obsahujím žádaný trimer, ovšem pouze Suzukiho-Miyaurova reakce poskytla uspokojivé výsledky. Rozpustnost připravených směsí však byla velice nízká, což znemožňovalo izolaci čistých produktů a další syntetický postup. V případě divinyltrimeru se podařilo provést finální metathesi. Vzniklá směs byla analyzována pomocí hmotnostní spektrometrie, která prokázala preferovaný vznik žádaného makrocyklu. Navzdory uvedeným problémům ponechávají dosažené výsledky prostor pro...The synthesis of large, shape-persistent, trimeric macrocycles comprising helical units was investigated. Since the previous synthetic approaches studied in our group failed (mainly alkene and alkyne ring closing metathesis), a more robust route toward the desired macrocycle was sought. A sequential construction of an acyclic trimer employing cross- coupling reactions was expected to overcome the unwanted oligomerization encountered in the case of the earlier metathesis approaches. The closure of the trimer would be accomplished via the intramolecular McMurry reaction or alkene metathesis. An optimized synthesis of the solubilized dibenzo[5]helicene and its derivatives was developed. These compounds served as proposed building blocks of the acyclic trimer. Both Heck and Suzuki- Miyaura couplings used for the preparation of the acyclic trimers provided mixtures containing the desired trimers but the Suzuki-Miyaura reaction proved to be much more efficient. However, the solubility of the trimers turned out to be very low, making the separation of the pure products from the mixture impossible and seriously limiting the further synthetic progress. Only alkene metathesis of the corresponding divinyltrimer was accomplished and despite a low solubility of the starting material, the MS analysis of the...Department of Organic ChemistryKatedra organické chemiePřírodovědecká fakultaFaculty of Scienc
Development of new methods for the synthesis of compounds containing the pyridine ring
Get PDFTato 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, inserc
Enantioselective amination pyrazolon derivatives
No full textDepartment of Organic ChemistryKatedra organické chemieFaculty of SciencePřírodovědecká fakult
Synthesis of amides of 3,4-benzotropolone-carboxylic acid
No full textTropolone and benzotropolone are both naturally occurring motifes with broad spectrum of bioactivities and interesting properities that are connected to these structures. This bachelor thesis explores preparation of 3,4,6-trihydroxy-5H-benzo[7]annulen-5-one, so called purpurogallin and it's possible preparation by enzyme catalyzed reactions and further synthetic use of these products. The study is mainly focused on synthesis of 3,4-benzotropolon- carboxylic acid, specially it's amides. First part deals with choosing the optimal reaction conditions for formation of these amides. In the next part palladium catalyzed carboxylations were performed on prepared bromoderivate of dehydroxypurpurogallin. Key words tropolones, benzotropolones, dehydroxypurpurogallin-4-carboxylic acid, amides, optimization, enzymatic catalysis, carboxylatio
Preparation of modified ligands of mu-opioid receptors
Get PDFThis diploma thesis deals with preparation of modified ligands of mu, delta and kappa opioid receptors, following up on the author's bachelor's thesis.1 The main goal of the submitted thesis is ligand tethering at an appropriate position using oligoethylene glycol linkers, to enable their use in the innovative iBodies concept.2 Ligands chosen for modifications were: naltrexone (μ-opioid receptor), naltrindole (δ-opioid receptor) and nalfurafine (κ-opioid receptor). Naltrexone was modified, according to the bachelor's thesis results, at the C-6 position with linker attachment via ether and amide. At the same time, the influence of the configuration at the newly formed C-6 stereogenic center on biological activity was studied. In case of naltrindole, access through indole nitrogen was chosen based on the information in literature.3-5 Nalfurafine was modified on the furane fragment. Series of fluorescently labeled ligands were prepared. Attachment of the fluorescent tag allowed us to study the affinity and selectivity of these modified ligands. Based on the results, ligands for development of DIANA method and for preparation of synthetic iBodies were synthesised.6 Key words: naltrexone, receptor, conjugate, opioid receptor 1 M. Hadzima. Fluorescenčně značené ligandy μ-opioidních receptorů, 2016. 2 P...
Synthesis of peptidic inhibitors targeting PA-PB1 interface of influenza RNA polymerase
Get PDFThe 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, polymeras
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