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Synthesis of beta-cyclodextrin derivatives for medicinal applications
Popr, Martin ; Jindřich, Jindřich (advisor) ; Veselý, Jan (referee)
Synthesis of monosubstituted β-cyclodextrin derivatives for medicinal applications Abstract This thesis is focused on preparation of a set of β-cyclodextrin derivatives with potential use as scaffolds for a construction of novel MRI contrast agents. Firstly, the skeleton of native β-CD was selectively persubstituted at possitions 6 and equipped with azide functions. Per-6-azido-β-CD was then monosubstituted on secondary face of the macrocycle. (E)-cinnamylbromide and propargylbromide were chosen as suitable reagents. The monosubstitution reaction afforded two types of regioisomers, substituted at position 2I -O- or 3I -O-. These regioisomers were sucessfully separated via preparative column chromatography after peracetylation of all free hydroxyl groups. 2I -O-, 3I -O-formylmethyl- and 3I -O- karboxymethyl- analogues were prepared by oxidative transformation of cinnamyl group. Finally the usability of the formylmethyl- derivative for covalent binding with suitable substrate via reductive amination was confirmed. Keywords: cyclodextrins, monosubstitution, cinnamyl, propargyl, formylmethyl, carboxymethyl, reductive amination, MRI, contrast agents
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Synthesis of oligonucleotide conjugates with molecules enhacing binding power to nucleic acids chains
Bernardová, Simona ; Miletín, Miroslav (advisor) ; Opletalová, Veronika (referee)
Distamycin A, netropsin, Hoechst 33258 and other are substances that bind in minor groove in the double helix of A·T base pairs DNA sequences. This diploma thesis describes the synthesis of compounds structurally derived from the model molecule distamycin A and their conjugation with oligonucleotides. Synthesis of compounds derived from distamycin A was performed by methods of peptide synthesis in solution and on solid phase. For preparation of desired compounds have been carried out a number of sectional reactions which were only partially successful. The most promising seems to be molecule tert-butyl-5- (5-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethylcarbamoyl)-1-methyl-1H-pyrrole-3- ylcarbamoyl)-1-methyl-1H-pyrrole-3-yl-carbamate.
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Preparation of organocatalysts derived from thiourea containing saccharide units
Řehůřková, Tereza ; Veselý, Jan (advisor) ; Smrček, Stanislav (referee)
4 ABSTRACT This diploma thesis is focused on the synthesis of new bifunctional thiourea organic catalysts containing a carbohydrate moiety, in particular D-glucose with modification on the primary hydroxyl group. The first part of this diploma thesis describes a modification of synthesis of the known bifunctional thiourea catalyst with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose and (1R,2R)-diaminocyclohexane. The second part is dedicated to the synthesis of new bifunctional thiourea catalysts with modification of the carbohydrate moiety. We focused on per-O-acetyl-β-D-glucopyranose derivatives with pefluoroalkyl moiety on the primary hydroxyl group. We examined different ways of the preparation of 6-O-perfluoroalkylated glucose derivatives. These perfluoroalkylated carbohydrate compounds were transformed into corresponding glycosyl isothiocyanates. Those derivatives upon treatment of (1R,2R)-diaminocyklohexane or 3,5- bis(trifluormethyl)aniline afforded new bifunctional thiourea organocatalysts.
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Synthesis of tetrazole derivatives as potential antituberculotics
Němeček, Jan ; Roh, Jaroslav (advisor) ; Vávrová, Kateřina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Jan Němeček Supervisor: PharmDr. Jaroslav Roh, PhD. Title of diploma thesis: Synthesis of tetrazole derivatives as potential antituberculotics Tuberculosis is a widespread infectious disease; however, no substances were introduced to the clinical practise during the last decade. In this diploma thesis, a series of potential antitubercular substances based on 1-substitued-5-alkyl/arylsulphanyl-1H-tetrazole were prepared. First, we prepared two compounds, 5-[(1-phenyl-1H-tetrazole-5-yl)sulphanylmethyl]-1H- tetrazole and 5-[(1-phenyl-1H-tetrazole-5-yl)sulphanyl]-1H-tetrazole, as the main building blocks, which were further functionalized. 5-[(1-phenyl-1H-tetrazole-5-yl)sulphanyl]-1H-tetrazole was substituted by methyl, propyl and benzyl groups on the terminal tetrazole ring. The same substitutions were performed with 5-[(1- phenyl-1H-tetrazole-5-yl)oxymethyl]-1H-tetrazole, which had already been prepared in our laboratory. Furthermore, we prepared 5-[(2-methyl-1,3,4-oxadiazole-5-yl)methylsulphanyl]-1-phenyl-1H- tetrazole, 5-[(2-methyl-1,3,4-oxadiazole-5-yl)sulphanyl]-1-phenyl-1H-tetrazole and 5-[(2-methyl- 1,3,4-oxadiazole-5-yl)methoxy]-1-phenyl-1H-tetrazole from the...
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Enantioselective synthesis of homoallylic alcohols using chiral N-oxide organocatalysts
Mikušek, Jiří ; Pour, Milan (advisor) ; Roh, Jaroslav (referee)
In order to extend the earlier work in the group,1 we endeavored to explore the ability of the terpene-derived pyridine N-oxide organocatalyst (+)-METHOX to catalyze allylations of non-aromatic, α,β-conjugated aldehydes with allyltrichlorosilane in CH3CN. This thesis describes the synthesis of 5 novel homoallylic alcohols of high enantioselectivities (≤ 96% ee). O HR + SiCl3 METHOX 10 mol% CH3CN -30 řC R OH * (S) 96% ee N+ O- OMe OMe OMe (+)-METHOX 1 Malkov, A. V.; Bell, M.; Castelluzzo, F.; Kočovský, P. Org. Lett. 2005, 7, 3219
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Terpyridine derivatives: preparation and complexation properties
Vitvarová, Tereza ; Svoboda, Jan (advisor) ; Sedláček, Jan (referee)
In this thesis we report synthesis of chosen terpyridine derivatives and their availability to make a complex with Zinc (II) ions and Iron (II) ions. These complexes were characterised and we studied their suitability to build supramolecular materials. Iron (II) complexes are more stable, but the Zinc (II) complexes are more suitable due to their good stability combined with great photophysical properties. We also report the polymerization of 4'-ethynyl-2, 2': 6', 2''-terpyridine as substance, which combines in the structure the possibility to make common covalent and non-covalent polymers. Last part of this thesis considers the synthesis of phosphole-based substances, which make as well as the terpyridine derivatives full conjugated system. Keywords: terpyridine, complexation, stability constant
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Synthesis of Zinc (II) Aryloxy Tetraquinoxalinoporphyrazines
Vůjtěch, Petr ; Zimčík, Petr (advisor) ; Kopecký, Kamil (referee)
A B S T R A C T Charles University in Prague Faculty of Pharmacy in Hradec Kralové Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Petr Vůjtěch Consultant: PharmDr. Petr Zimčík Ph.D. Title of Thesis: Synthesis of Zinc (II) Aryloxy Tetraquinoxalinoporphyrazines The aim of my master thesis was synthesis of tetra[6,7]quinoxalinoporhyrazine derivative (TQP). Advantage of TQP is bathochromic shift when compared to azaphthalocyanines (AzaPc), which is more appropriate for PDT. AzaPc and TQP derivatives are large planar and conjugated systems, which tend to form aggregates. The aggregation is unfavorable property of TQP derivatives that reduces the singlet oxygen quantum yield. The most effective strategy to increase the ratio monomer/aggregates involves the use of bulky substituents attached to the TQP periphery. That is the reason why I focused on synthesis of 2,3,11,12,20,21,29,30-octa(2,6-diisopropyphenoxy)-tetra [6,7]qinoxalinoporphyrazinato zinc(II). Alkoxides cannot be used for cycloteramerization of aryloxy derivatives due to the well-described transetherification problems. As was shown in my diploma thesis the best way to synthesis of aryloxy derivatives of AzaPc is reaction with Zn(quinoline)2Cl2 in a melt. That is why this method was applied also for TQP derivatives. Kinetic of...
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Use of Microwave Heating in the Synthesis of Novel Polysaccharide Derivatives.
Taubner, T. ; Synytsia, A. ; Sobek, Jiří ; Kortanková, V. ; Čopíková, J.
Microwave-assisted modification of polysaccharides is a relatively new method. Microwave heating is used for improving of extraction, hydrolytic and synthetic procedures. Modification of polysaccharides with the microwave irradiation is effective, fast and economic. The aim of this study was to apply the microwave irradiation in synthesis of carboxymethylcellulose (CMC) derivatives. This polysaccharide and its methyl ester reacted with n-butylamine yielding N-butylamide. The reactions were subsequently monitored by FUR and organic elemental analysis of the products. Degree of substitution (DS) and reaction yields were calculated based on nitrogen and carbon contents. The optimal reaction conditions were found to prepare product with the highest DS. Amino-de-alkoxylation of CMC methyl ester was significantly more effective than direct microwave assisted amidation of CMC, and microwave assisted significantly improved amino-de-alkoxylation.
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Anion receptors based on symmetrically tetrasubstituted calix[4]arenes
Klimentová, Jana ; Lukeš, Ivan (advisor) ; Budka, Jan (referee) ; Trávníček, Zdeněk (referee)
The submitted Ph.D. thesis concerns anion receptors based on symmetrically tetrasubstituted cone calixf4]arenes. These receptors are easily synthesized and display sufficient water solubility to function as receptors for tetrahedral oxoanions. The thesis starts with a brief survey of literature on calix[4larene anion receptors and sensors. The theoretical part of the thesis deals with a stereochemical investigation of calixf4]arenes from the Cambridge Structural Database (CSD) with emphasis on the influence of inter- and/or intramolecular interactions on the geometry and rigidity of the calix[4]arene scaffold. In order to describe the geometry of the calixf4]arene moiety, it was necessary to introduce new stereochemical parameters cr, B and 5. The utility of these parameters in evaluating the geometry of the calixf4]arene base frame was confirmed. The stereochemical investigation formed the basis for design of new potential anion receptors based on symmetric al ly tetrasub stituted c o n e calixl4 ] arene s. The experimental part of this work started with synthesis of symmetrically tetrasubstituted calixf4]arene derivatives containing 1-propoxy groups at the lower rim and synthesis of calixf4]arene derivatives with carboxymethoxy groups at the lower rim and enhanced water solubility. Identity and...
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Synthesis of 1,4-phosphonic and phosphinic acid derivatives of cyclen
Bárta, Jiří ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
Title: Synthesis of 1,4-phosphonic and phosphinic acid derivatives of cyclen Author: Bc. Jiří Bárta Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: Doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail adress: modrej@natur.cuni.cz Abstract This thesis is focused on synthesis of diphosphonic and diphosphinic derivatives of cyclen at 1,4 positions as potential MRI contrast agents. Preparation of 1,4-dibenzylcyclen was optimized in a gramme scale for synthesis of derivatives mentioned above. 1,4-dibenzyl-7,10-bis(diethylphosphonomethyl)cyclen was prepared in a gramme scale. It's fully hydrolyzed and monoester forms were prepared. 1,4-bis(diethylphosphonomethyl)cyclen was synthesized. It's fully hydrolyzed and monoester forms were synthesized. 1,4-dibenzyl-7,10- bis(phosphinomethyl)cyclen was synthesized. The carboxylic function in ester form was attached on diesterphosphonic derivative of cyclen. Altogether 8 derivatives in positions 1,4 and 7,10 of cyclen was prepared, mostly in a gramme scale and with a high yield. All compounds were characterized by NMR and MS. Key words: cyclen, phosphonate, phosphinate, sythesis, MRI
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