National Repository of Grey Literature 14 records found  1 - 10next  jump to record: Search took 0.01 seconds. 
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
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
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...
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.
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
Synthesis of fluorinated nucleosides
Nguyen, Van Hai ; Hocek, Michal (advisor) ; Baszczyňski, Ondřej (referee)
The key intermediate 6-amino-7-iodo-7-deazapurine 3'-deoxy-3'-fluororibonucleoside was synthesized using multistep sequence of several reactions, which started from the commercially available D-xylose and 6-chloro-7-deazapurine. The synthetic strategy was based on fluorination of sugar and glycosylation with corresponding nucleobase afterwards. The fluorination of 5-protected-1,2-isopropylidine xylose with different protecting groups at position 5 always led to elimination. It was later discovered that isopropylidine forces the conformation, which is unfavorable for substitution. During the extensive optimization it was also found out that DAST appears to be an optimal fluorinating agent. Fluorination was performed on 2,3-unprotected xylose, which was subsequently used for glycosylation. After several unsuccessful attempts on "protection group free" glycosylation, Vorbrüggen glycosylation was successful and gave desired 3'-fluoro nucleoside in good yield. However, benzoyl group had to be introduced into position 2'. The protected nucleoside was then aminated and simultaneously deproctected with solution of aqueous NH3 and 1,4-dioxane. The obtained key intermediate was used for synthesis of a small series of desired 6-amino-7-hetaryl nucleoside using Pd-catalyzed Suzuki reaction under aqueous...
2-(Phosphonomethoxy)ethyl derivatives of 6-fluoro-3-hydroxypyrazine-2-carboxamide
Lamačová, Lucie Josefa ; Jindřich, Jindřich (advisor) ; Baszczyňski, Ondřej (referee)
This bachelor thesis deals with the preparation of derivatives of acyclic nucleoside phosphonates with nitrogenous base favipiravir. There are many examples of acyclic nucleoside phosphonates that are used as antiviral drugs due to their structure. Favipiravir shows antiviral activity against the influenza virus. The target compounds thus might have the potential to be biologically active, which will be tested in virological laboratories at KU Leuven in Belgium. First, the methods for preparation of 2-(phosphonomethoxy)ethyl derivative of favipiravir was designed, then for its diphosphate and a prodrug with pivaloyloxymethyl groups to increase the bioavailability of the compound. Thus, 2-(phosphonomethoxy)ethyl derivatives of favipiravir and its de-fluoro analogue were prepared. Key words: acyclic nucleoside phosphonates, T-705, favipiravir, T-1105, influenza, antiviral activity

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