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Novel NMR Method for Organic Aerosol Analysis
Horník, Štěpán
The suitability of ChenomX was performed both on real atmospheric aerosols and model samples of coal combustion. Up to 30 compounds were found in analyzed samples. Most abundant substances were mono- and dicarboxylic acids (formic, acetic, succinic acid) and their derivatives (lactic acid), followed by carbohydrates, anhydro saccharides and sugar alcohols (levoglucosan, fructose, D-threitol), and amines (methylamine, dimethylamine). The real aerosol sample was also analyzed on four different NMR spectrometers (500, 600, 700, 800 MHz) in order to enhance the resolution and find less abundant substances. The frequencies of the spectrometers were chosen according to the ChenomX database. In the 800 MHz spectrum ca. 50 compounds were identified.
Fulltext: content.csg -  PDF
Plný tet: SKMBT_C22015061709380 - PDF
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Synthesis of cyanobenzamide derivatives with anthelmintic activity
Flídrová, Lucie ; Špulák, Marcel (advisor) ; Macháček, Miloš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Lucie Flídrová Consultant: PharmDr. Marcel Špulák, PhD. Title of Thesis: Synthesis of cyanobenzamide derivatives with anthelmintic activity The goal of this work was to prepare four of the most active known cyanobenzamides from the new promising anthelmintic group (aminoacetonitriles - AADs). Synthesis of first three compounds was carried out by alkylation of the corresponding phenol with chloroacetone followed by the Strecker reaction of ketone and acylation of the amine with substituted benzoylchloride. For the fourth derivative, alternative synthesis was established. THP-protected hydroxyacetone was used as a substrate for the Strecker reaction, which was followed by the acylation with substituted benzoylchloride. Finally aromatic nucleophilic substitution of activated fluorobenzene yielded the targeted compound. All prepared derivatives were synthesized in good yields. Compounds are currently being tested at the Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové to explore the relationship between drug metabolizing enzymes (DME) and drug resistance.
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Synthesis of NK1 antagonists.
Puchnerová, Lucie ; Doležal, Martin (advisor) ; Zitko, Jan (referee)
Synthesis of NK-1 antagonists Lucie Puchnerová Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy University of Seville NK-1 receptor antagonists are represented so far by only one drug, Aprepitant, which is available on the market for prevention of chemotherapy-induced nausea and vomiting. Nevertheless, it is assumed that NK-1 antagonists will be able to participate in treatment of migraine, rheumatoid arthritis, asthma, pain, inflammatory bowel disease, Parkinson's disease, anxiety and depression in future. This thesis is concerned with asymmetric synthesis of derivatives of 2-amino-4H-pyran, which thanks their substitutions are in accordance with structure of pharmacophore of NK-1 antagonists. As a starting material for their preparation has been used commercial methyl p-tolyl sulfone and (R)-methyl p-tolyl sulfoxide, which was synthesized from menthyl-(S)-p- toluenesulfinate by nucleophilic substitution. These compounds were subjected to reaction with ethyl 2-picolinate. From prepared β- ketosulfoxide and β-ketosulfone were obtained 2-amino-4H-pyrans by Michael addition. The derivatives proceeding from β-ketosulfoxide were subjected to reduction of the sulfoxide and trifluoroacetylation of the amine group on the carbon 2 of the pyran ring. Prepared derivatives had agonistic activity...
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Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II
Břečková, Anna ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Břečková Supervisor: Přemysl Mladěnka, Ph.D. Title of Thesis: Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II Iron deficiency and iron overload play important roles in the pathophysiology of certain human diseases. Administration of iron chelators is a suitable therapy in iron overload conditions, especially in cases of hematological diseases treated with blood transfusions. Iron- chelating therapy appears as well as a promising tool for other diseases (acute myocardial infarction, tumor, etc.). Several factors should be considered according to expected indications: 1) oral efficiency, 2) activity in acidic environment, 3) ability to reduce ferric ions to ferrous ions (risk of pro-oxidation). The aim of this thesis was to verify the iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group by use of UV-VIS spectrophotometric methods. From this group, p-terc.butyl- and p-nitroderivatives of the basic structure and the derivatives marked as H2Q3Q and H2QPy, which are double molecules of the basic structure, were chosen. All of the tested substances had some potential to chelate ferrous ions and were also devoid of...
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Analysis of amino acids and polyamines by HPLC and CZE
Kubíčková, Anna
(EN) This work is focused on two specific classes of amines. First group comprises of cyclic polyaminocarboxylates from the DOTA (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) family, which are important reaction intermediates in magnetic resonance imaging (MRI) contrast agent synthesis. In the development of new contrast agents, carboxyl groups are very often protected with tert-butyl ester groups. Among these derivatives, tBu3DO3A is of the highest importance. Therefore, reverse-phase high performance liquid chromatographic (RP-HPLC) and non- aqueous capillary zone electrophoretic (CZE) methods were evaluated for qualitative and quantitative analysis of tBu3DO3A (1,4,7,10-tetraazacyclododecan-1,4,7- tris(tert-butylacetate) and two typical reaction by-products, i.e. tBu4DOTA (1,4,7,10- tetraazacyclododecan-1,4,7,10-tetrakis(tert-butylacetate) and tBu2DO2A (1,4,7,10- tetraazacyclododecan-1,4-bis(tert-butylacetate). These optimized methods were successfully applied to monitoring of real reaction mixtures during synthesis of a new MRI contrast agent. No further sample pretreatment was necessary. In the second part of the thesis, proteinogenic amino acids and polyamines were used as model analytes for development of a new post-column solid-phase reactor suitable for on-line derivatization...
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Properties of bipyridine N,N'-dioxides in the gas phase
Ducháčková, Lucie ; Kotora, Martin (referee) ; Roithová, Jana (advisor)
Lucie Ducháčková Bipyridine N,N'-dioxides are organocatalysts, which are used as a chiral Lewis bases in enantioselective catalysis. The aim of this diploma thesis was systematic investigation of the proton affinities of bipyridine N,N'-dioxide derivatives. Further, the complexation properties and chiral recognition in the gas phase of bipyridine N,N'-dioxide derivatives were examined. Mass spectrometry complemented with infrared multiphoton dissociation spectroscopy and quantum-chemistry calculations using the density functional theory (DFT) were used as the main experimental methods. Bipyridine N,N'-dioxides are a new class of oxygen superbases with proton affinities larger than 1030 kJ/mol. Complexation properties and reactivities of their metal complexes are comparable to 2,2'-bipyridine.
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Derivatives of pyrazine as potential antituberculotics
Osička, Zdeněk ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
Mgr. Zdeněk Osička: Pyrazine Derivatives as potential antituberculous drugs I have focused on the synthesis of compounds from the class amides of substituted pyrazinoic acid in my Pharmacy Doctor Thesis. Series of compounds were prepared by the reaction of pyrazinoic acid chloride with corresponding amines. Synthesis underwent in two steps. Final compounds were characterized by the melting point, TLC, elementary analysis, 1H a 13C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis testing the activity grew up from the least to the most lipophility compound.
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Modulární metodiky pro přípravu různých aryl C-2'-deoxyribonukleosidů
Joubert, Nicolas ; Bárta, Jan ; Urban, Milan ; Hocek, Michal
A modular methodology for the syntheses of various substituted aryl C-2´-deoxyribonucleosides has been developed. In each series, a larger scale synthesis of a versatile halogenated C-nucleoside intermediate has been accomplished, followed by its use for a generation of diverse derivatives by displacement of the halogen for alkyl, aryl or amino substituents by cross-coupling or amination reactions. Subsequent deprotection gave the final desired C-2´-deoxyribonucleosides. This methodology has been applied for the development of modular syntheses of 4- or 3-substituted benzene C-nucleosides, 6-substituted pyridin-2-yl C-nucleosides, 6-substituted pyridin-3-yl C-nucleosides and 5-substituted thiophen-2-yl C-nucleosides.
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Picolinamide Derivatives of N-Methyl Valine as New Possible Chiral Organocatalysts in the Enantioselective Reduction of Aromatic Ketimines with Trichlorosilane
Bešťák, Petr ; Pour, Milan (advisor) ; Vinšová, Jarmila (referee)
N O 5, Cl3SiH (60%, 28%ee) HN PMP H MePh HN PMP MePh H R; 36% + S; 64% 1a 1aa 1ab NH O O O Ph NH PMP O O H Ph NH PMP O O H + (90%, 22%ee) R; 39% S; 61% 5, Cl3SiH 1b 1bb 1ba A N H O O N H N ON Ph Ph OH B O 5, Cl3SiH (49%; ee's unknown) OH OH + 2a 2aa 2ab O 5 (32%; ee's unknown ) OH OH + SiCl3, 3a 3aa 3ab N O O HN 5 N N O O HN 5a N O A Diploma Thesis Abstract : Picolinamide Derivatives of N-methyl Valine Used as New Possible Chiral Organocatalysts in the Enantioselective Reduction of Aromatic Ketimines with Trichlorosilane. Petr Bešťák, 5th grade Supervisor: Prof. RNDr. Milan Pour, Ph.D. Katedra anorganické a organické chemie, Farmaceutická fakulta UK v Hradci Králové Chiral substances have become popular for pharmaceutical industry recently, due to the differences between enantiomers' and racemate's efficiency and/or safety. Asymmetric organocatalysis is a perspective approach in the synthesis of chiral substances, used as new drugs or their synthons. No doubt that this way is cheaper and easier than methods using splitting a racemic mixture. This method was developed as an attractive alternative of transition metals-using procedures (with Pd, Ir, Ti), while completely excluding their toxicity, limited usage and high costs. Chiral reduction of N-aryl ketimines like 1a, 1b with trichlorosilane can be...
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