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Reactions of Alkenes Iniciated by Transition Metals Alkyls and Hydrides
Nečas, David ; Kotora, Martin (advisor) ; Jindřich, Jindřich (referee) ; Starý, Ivo (referee) ; Mazal, Ctibor (referee)
l0 5. Conclusion 1) The first and practical catalýic method for smooth deallylation of 2-substituted-2-allylmalonates to 2-substituted malonates via selective cleavage of the C-C bond under mild reaction conditions has been developed' The reaction seems to be general with respect to the transition-metal complexes; however, the comparison of Ru and Ni catalysts indicates considerable differences in their specific activity and selectiviý. Last but not least, the smooth deallylation offers an opportuniý to use the allyl group as an effective protective group for acidic hydrogen of malonic esters. 2) It has been shown that it is possible to re-route the course of the reaction from c{ bond cleavage (deallylation) to c{ bond formation (cyclization) in Ni hydride cataryzed, reactions by a change in the amount of organoaluminium. It proceeded in high yields even in cases where deallylation could compete with cyclization (e.g. diallylmalonate, etc.) in high selectiviý. In addition, generation of Ni hydride species in sinr provides an effective means for fast and selective cyclization of variously substituted 1,6- heptadienes to cyclopentanes. Moreover, it is possible exert certain level of control for the preferential formation of methylidene(methyl)cyclopentanes or cyclopentenes by the appropriate choice of thb...
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β-Cyclodextrin conjugates with selectively methylated rims
Lebedinskiy, Konstantin ; Jindřich, Jindřich (advisor) ; Lhoták, Pavel (referee) ; Kraus, Tomáš (referee)
β-Cyclodextrin conjugates with selectively methylated rims The current doctoral thesis focuses on studying cyclodextrin conjugates with selectively methylated rims and testing their potential applicability for solubility enhancement and guest- specific complexation. This work's principal aim is to develop new synthetic methods for the preparation of monofunctionalized β-cyclodextrin derivatives with selectively methylated rims and their further transformations into operating conjugates. The thesis is divided into four sections - preparation of monoazido-β-cyclodextrin derivatives with selectively methylated rims and some conjugates from them; direct transformation of the prepared azides into corresponding monoamines and monohalides that enables the synthesis of other types of conjugates; testing the potential of the prepared conjugates for tetracene solubility increase in different media and selective binding of one component from a mixture of steroid substances; finally, the work explores the complexation of some noradamantane molecules with natural cyclodextrins and the phenomenon of guest's signals splitting in their 13 C-NMR spectra. Keywords: cyclodextrin conjugates, bisCDs, selective methylation, selective binding, solubility enhancement
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Quantification of the stabilizing effects of cyclodextrins on volatile biocides using spectral methods
Konovalova, Olga ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This bachelor's thesis deals with monitoring the stability of chlorine dioxide of native and methylated cyclodextrins in the presence of hydrogenating agents. It is believed that using cyclodextrins and carboxymethylcellulose can improve the stability of chlorine dioxide and slow its release from the solution. UV spectroscopy was used to monitor any changes in absorbance over time and to determine the concentration of chlorine dioxide in the solution. When the rate of chlorine dioxide loss from solution was monitored, it was found that the presence of native and permethylated cyclodextrins slowed the loss of chlorine dioxide from solution, with the slowest decomposition observed in the presence of permethylated cyclodextrin. The addition of carboxymethylcellulose to the chlorine dioxide solution slows the rate of chlorine dioxide loss from the open vial the most, by almost three times, compared to ClO2 itself. This study's results can help optimize chlorine dioxide product formulation for various applications and contribute to the development of more stable and effective chlorine dioxide- based products that can be used to control or eliminate harmful microorganisms in different environments. Key words: chlorine dioxide, CDS, cyclodextrins, carboxymethylcellulose, biocides, UV-Vis...
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Synthesis of self-immolative linkers suitable for bioconjugation
Taraj, Lukáš ; Baszczyňski, Ondřej (advisor) ; Jindřich, Jindřich (referee)
Self-immolative (SI) linkers are chemical constructs that undergo controlled self- fragmentation based on an appropriate stimulus, e.g., activation by light or a chemical agent. SI linkers are used in the targeted delivery of drugs, in the construction of probes for biochemistry, or in various polymers. The aim of the thesis will be the synthesis of new phosphorus-based SI linkers, which will contain a reactive chemical function for conjugation with thiols. Such a function will be, for example, a vinyl phosphonate or alkynyl phosphonate group. The aim of the work will be to examine the synthesis, self-immolation, stability, and the possibility of conjugability of such linkers with thiols, e.g., cysteine, glutathione, etc. The content of the student's work will be the synthesis of SI linkers, analysis of the obtained data, planning and monitoring of chemical experiments, and writing the diploma thesis. Keywords: self-immolative, bioconjugation, phosphorus, drug delivery
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Synthesis of cyclodextrin derivatives suitable for binding to solid supports
Kasal, Petr ; Jindřich, Jindřich (advisor) ; Kraus, Tomáš (referee) ; Lhoták, Pavel (referee)
Synthesis of cyclodextrin derivatives suitable for binding to solid supports This presented doctoral thesis studies the preparation of new cyclodextrin (CD) derivatives suitable for binding to solid supports. This work aims to develop synthetic protocols for monosubstituted and selectively persubstituted CD derivatives possessing permanent positive charges. These compounds have the potential to be electrostatically bound to negatively charged supports, including silica gel, alumina, Nafion® , cation exchange resins, etc. Compared to the covalent bond, the advantages of this electrostatic binding are mainly the easiness of modification and maintenance. Dipping solid support for a defined time into a solution of charged CD derivatives should ensure the bond between positively and negatively charged partners. Thus, this thesis is divided into several parts. The first part covers the preparation of neopentyl skeleton compounds (anchors) bearing positive charges suitable for ionic bonding with negatively charged solid supports, and a reactive functional group suitable for a reaction with CD derivatives. The first partially successful synthetic tries are described, together with various leaving groups kinetic studies performed by NMR spectroscopy. The final synthesis of anchors developed with potential...
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Development of a heterogeneous catalytic system using multiply charged cyclodextrins and proline-based organocatalysts
Zelený, Jan ; Jindřich, Jindřich (advisor) ; Baszczyňski, Ondřej (referee)
Cyclodextrins are a class of organic molecules consisting of a cyclic system of α(1→4) linked glucose units. These compounds possess a range of interesting properties and can be derivatised to suit various industrial and scientific purposes. Among their derivatives are so- called multiply charged cyclodextrins, the development and application of which is an essential part of our group's research interest. These cyclodextrin derivatives are capable of binding electrostatically to different solid sorbents, such as silicagel or alumina. This electrostatic interaction is mediated by an array of permanently positively charged moieties which are covalently attached to the primary rim of a cyclodextrin unit. The free secondary rim then offers the possibility of further derivatisation and functionalisation of this system. The resultant cyclodextrin derivative represents a modular scaffold which can be used to immobilise different functional components. This project focuses on the application of this system to the immobilisation of a Hayashi- Jørgensen-type catalyst for the purposes of heterogeneous catalysis. The work includes the assembly of the of the chosen catalytic system from its precursors and also the synthesis thereof. Furthermore, the resulting supramolecular system is tested for its catalytic...
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Synthesis of multiply negatively charged anchors with sulfonate groups
Tomanová, Adéla ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The scope of the bachelor thesis is the synthesis of derivatives derived from the neopentyl skeleton, containing one detection or reactive group and one, two or three sulfonate groups. These compounds have applications for the preparation of molecules capable of electrostatic self-assembly, useful, for example, for modifying positively charged surfaces of stationary phases (e.g. aminopropyl silicagel) in chromatography. Keywords: modification of charged surfaces, sulfonate groups, neopentyl derivatives
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I.Synthesis of acyclic nucleoside phosphonates with a thiadiazole base mimicking 5-azacytosine as compounds with potential biological activitiesII.Development of small molecules targeting c-MYC oncogene.
Pomeislová, Alice ; Krečmerová, Marcela (advisor) ; Jindřich, Jindřich (referee) ; Voltrová, Svatava (referee)
The first part of the thesis regards synthesis of N-[2-(phosphonomethoxy)ethyl] (PME) and (S)-3-hydroxy-2-(phosphonomethoxy)propyl ((S)-HPMP) derived acyclic nucleoside phosphonate (ANP) analogues carrying 5-amino-1,2,4-thiadiazol-3(2H)-one as a nucleobase that is supposed to mimic cytosine or 5-azacytosine. A series of 1,2,4-thiadiazole derivatives bearing at the N2 position PME- or (S)-HPMP-moiety and NH2-protecting group (benzoyl, ethoxycarbonyl, or Fmoc) were obtained as chemically stable ANP congeners. Their synthesis was performed via stepwise construction of the thiadiazole ring and required the use of two newly prepared synthons, PME-amine and (S)-HPMP-amine. However, all attempts to prepare the intended PME- and (S)-HPMP-thiadiazole phosphonic acids with free amino moiety failed due to instability of the N2 -substituted thiadiazole ring. Biological evaluation of twenty-one selected thiadiazole compounds towards two human cysteine- dependent enzymes, cathepsin K and glycogen synthase kinase 3ß, revealed that several compounds inhibited both enzymes in the low micromolar range. Some of these efficient inhibitors had also favourable toxicity profile at 100 µM, which makes them appropriate for further development of potential drug candidates. In the second part of the dissertation, design and...
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