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Preparation of myo-inositol derivatives
Kurčina, Adam ; Kamlar, Martin (advisor) ; Baszczyňski, Ondřej (referee)
Phosphoinositides are naturally occurring molecules with vast range of biological activity important for cell life and survival. The exact role and mechanism of phosphatidylinositol 4,5-bisphosphate's actions are not yet elucidated. This bachelor's thesis is dedicated to the synthesis of selectively protected myo-inositol derivative suitable as precursor for synthesis of phosphatidylinositol 4,5-bisphosphate derivatives. Key words: Inositol, protective groups, regioisomers
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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 spirocyclic compounds containing quaternary carbon centres
Výbošťoková, Júlia ; Matoušová, Eliška (advisor) ; Baszczyňski, Ondřej (referee)
The main focus of this bachelor thesis is the preparation of spirocyclic compounds containing quaternary carbon centres. The key steps of the synthesis were palladium catalysed tandem cyclisation/Suzuki cross-coupling and subsequent halocarbocyclisation. The next step was oxidative opening of the tetrahydrofuran ring and following derivatisation of the resulting spirocyclic products. The prepared spirocyclic compounds will be tested for their possible cytotoxic effects. The first part of this work describes the preparation of starting materials which were subsequently subjected to the tandem cyclisation/Suzuki cross-coupling and halocarbocyclisation to form a quaternary carbon centre. In the second part, various oxidative conditions for tetrahydrofuran ring opening to form spirocyclic compounds are discussed. The last part of this work deals with the derivatisation of the synthesised spirocycles. Keywords: synthesis, spirocyclic compounds, quaternary carbon centres, cytotoxicity
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Synthesis of model, self-immolative, phosphate-based linkers for delivery of oximes
Kárníková, Tereza ; Baszczyňski, Ondřej (advisor) ; Matoušová, Eliška (referee)
This bachelor thesis explores a possibility of preparation and usage of oxime prodrugs. Thesis aim is to deliver oximes by using self-immolative phosphorous-based linkers that undergo cyclization reaction, leading to the release of oxime from the phosphorous. For this purpose, model systems containing: (1) a photolabile DMNB group, or they could contain enzymatically activable ester group, (2) self-immolative arm with the phosphate core, and (3) oxime as the leaving group, were prepared. Acetophenone oxime, cyclohexanone oxime, and griseofulvin oxime were used as the model oximes. In particular, the synthesis of target molecules and their self-immolation (i.e., controlled breakdown) have been studied. These reactions were monitored by 31 P NMR spectroscopy. The stability study of the prepared substances in buffer solutions has also been performed. Key words: oxime, prodrug, self-immolation, self-immolative linkers, photoactivation
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Synthesis of analogues of natural alkaloids containing quaternary carbon centres
Sádková, Michaela ; Matoušová, Eliška (advisor) ; Baszczyňski, Ondřej (referee)
This bachelor thesis is concerned with organic synthesis of polycyclic compounds containing quarternary carbon centres, which are structurally similar to Amaryllidaceae and Sceletium alkaloids. The aim of this work was to prepare compounds suitable for biological activity screening. To obtain the quarternary carbon centre, two key steps were used - tandem cyclisation/Suzuki cross-coupling and halocarbocyclisation. The first part of this work is focused on the synthesis of starting materials with two types of silyl groups. The second part deals with the preparation of quarternary carbon centre using tandem cyclisation/Suzuki cross-coupling and halocarbocyclisation. In the last part, experiments to form a double bond are described, together with its derivatisation to synthesise compounds with a potential biological activity. Key words: synthesis, alkaloids, Amaryllidaceae, Sceletium, polycyclic compounds, quarternary carbon centres
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Modified ribonucleotides as building blocks for enzymatic construction of functionalized RNA or as antiviral compounds
Milisavljević, Nemanja ; Hocek, Michal (advisor) ; Baszczyňski, Ondřej (referee) ; Krečmerová, Marcela (referee)
The aim of this thesis was to study the steric influence of the base-modified nucleoside triphosphates (NTPs) on the enzymatic incorporation into RNA, as well as to study their inhibitory effect on different viral RNA polymerases in vitro. Their parent nucleosides and prodrug derivatives were also prepared and their antiviral activity evaluated. In the first part of the thesis, NTPs bearing groups varying in size from small methyl and ethynyl substituents via medium-size phenyl and benzofuryl groups, up to large dibenzofuran ring were prepared. Aromatic substituents were installed via Suzuki coupling on iodinated triphosphates or, in the case of modified guanosines, by the phosphorylation of modified nucleosides. Methyl and ethynyl NTPs were prepared via Pd-catalyzed coupling with AlMe3 and Sonogashira coupling, respectively, followed by the phosphorylation of modified nucleoside. To examine their incorporation into RNA by T7 RNA polymerase, templates coding for 35mer RNA containing one, three or seven modifications were designed. Modified pyrimidine triphosphates worked well for all the sequences, while the biggest dibenzofuryl group was not accepted in the difficult sequence with seven modifications. In the case of AR TPs dibenzofuryl modification did not incorporate at all, while other...
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Catalytic Enantioselective Desymmetrization of meso-Epoxides
Malatinec, Štefan ; Kotora, Martin (advisor) ; Baszczyňski, Ondřej (referee)
Catalytic enantioselective desymmetrization of meso-epoxides is widely used in many areas of chemistry. Such process is usually catalyzed by a transition metal complex with a chiral ligand. Recently, a synthesis of an analogue of Bolm's 2,2'-bipyridine ligand was developed and its combination with metal salts were tested in various reactions. In this master's thesis, a catalytic system composed of Sc(OTf)3/Bolm's ligand analogue was studied in alcoholysis and aminolysis of the meso- epoxides. The reaction has been extended to a broad range of alcohols providing 1,2-diol monoethers in excellent enantioselectivity up to 99% ee. The aminolysis of meso-epoxides has been optimized, as well. The catalyst loading could be lowered to 1 mol% with only marginal effects on the enantioselectivity. Key words: epoxides, enantioselective catalysis, chiral ligands.
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Using levoglucosenone in the synthesis of naphthoquinone containing compounds
Neumannová, Johana ; Matoušová, Eliška (advisor) ; Baszczyňski, Ondřej (referee)
This bachelor thesis is focused on using levoglucosenone in the synthesis of the naphthoquinone containing compounds. Levoglucosenone is a versatile and easily available substance which can be prepared by pyrolysis of renewable cellulose-containing materials. The synthesis of the target compound begins with the preparation of the substrate for the tandem reaction (propargyl ether) in three steps. The following key steps of the synthesis include palladium-catalyzed tandem cyclization/Suzuki cross coupling and subsequent Heck reaction. Oxidation of the prepared methoxy-substituted naphthalene yields the o-naphthoquinone, which has a similar structure as some naturally occurring substances with naphthoquinone skeleton, e.g. mansonone D and populene C. Key words: Synthesis, naphthalenes, naphthoquinones, levoglucosenone, catalysis, polycyclic compounds
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