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Using N-hydroxysuccinimidyl formate as a CO source in tandem reactions
Bahramian, Artur ; Matoušová, Eliška (advisor) ; Smrček, Stanislav (referee)
This bachelor thesis deals with the use of N-hydroxysuccinimidyl formate as a source of CO in tandem reactions. The prepared starting materials were used in a tandem reaction involving cyclic carbopalladation, carbonylation and cross-coupling. The first part of the thesis describes the synthesis of starting material with a six-membered ring and of the selected CO surrogate. These compounds were subjected to a tandem reaction to form a product with a carbonyl group. Furthermore, the reaction conditions were studied and then the efficiency of using the selected formate compared to the gaseous carbon monoxide was compared. Keywords: synthesis, tandem reaction, cross-coupling, N-hydroxysuccinimidyl formate, carbon monoxide
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Synthesis of Alkaloid-like Compounds with Quaternary Carbon Centers
Jansa, Petr ; Matoušová, Eliška (advisor) ; Baszczyňski, Ondřej (referee) ; Nováková, Veronika (referee)
Synthesis inspired by natural products has a long tradition in drug development. Because the structure of bioactive natural compounds is often very complex, preparation of their derivatives requires the development of specific synthetic procedures. This thesis focuses on derivatives of certain alkaloids from the Amaryllidaceae plant family as examples of such compounds. The thesis explores the possibilities of preparing polycyclic compounds that contain the structural motif present in tazettine, crinine, or mesembrine-type alkaloids. This motif includes a quaternary all-carbon center, for which a method involving a tandem cyclization/Suzuki coupling reaction and a halocarbocyclization was developed and optimized in this work. The scope of these reactions was studied, and variously substituted products containing oxygen and nitrogen cycles were prepared. Furthermore, methods for the synthesis of N-alkylated derivatives, dehydrohalogenation to form a double bond, or various mainly oxidative modifications of the cycle adjacent to the aromatic ring were developed. After developing a method for the preparation of enantiomerically enriched starting material, an asymmetric version of the entire synthesis was successfully performed. Finally, biological properties of selected compounds were studied. Some...
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Synthesis of selagibenzophenone C and derivatives for confirmation of the stucture of the natural product.
Kunák, Dominik ; Rýček, Lukáš (advisor) ; Matoušová, Eliška (referee)
5 Abstract This bachelor's thesis deals with the preparation of selagibenzophenone C. The natural product was prepared in a six-step synthesis, where subsequent analysis and comparison of the spectrum of the synthetic substance with the spectra described for the isolated product verified whether the structure of the isolated natural product was deciphered correctly. Furthermore, it was verified that intermediates in the synthesis of selagibenzophenone C can undergo cyclization reactions to form a fluorene core. Analogous cyclization is the main step in the biosynthesis of selaginpulvilins from the corresponding selaginellins. The obtained fluorene derivatives will therefore be used as standards in the following studies to determine whether these substances obtained by us are also natural compounds. Key words Total synthesis, natural product, polyphenols, natural fluorene derivates, selagibenzophenones
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Synthesis of Novel Fused N-Heterocyclic [2.2]Paracyclophanes Using C-H Activation/Annulation
Kepková, Klementýna ; Nečas, David (advisor) ; Matoušová, Eliška (referee)
This bachelor thesis is focused on the development of a new methodology leading to a novel type of N-heterocyclic [2,2]Paracyclophanes (we can also view these compounds as isoquinoline derivatives) based on directed C-H activation/annulation process. Within the thesis, necessary [2,2]Paracyclophane derivatives containing appropriate directing group and non-commercial alkynes have been prepared. Suitable catalytic conditions for the C-H activation/annulation reaction sequence have been found and subsequently optimized. Finally, to demonstrate the applicability of that method, several new N-heterocyclic [2,2]Paracyclophane derivatives have been prepared and characterized successfully. Key words: [2.2]Paracyclophane, C-H activation, annulation, Isoquinoline, directing group
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Using tandem cyclisation/Sonogashira cross-coupling in the synthesis of natural products and their derivatives
Liška, Benno ; Matoušová, Eliška (advisor) ; Míšek, Jiří (referee)
The subject of this bachelor's thesis is the preparation of polycyclic compounds using the tandem cyclisation/Sonogashira cross-coupling and a potential application of this reaction to the synthesis of natural products and their derivatives. The aim was to study this method using nonaromatic starting materials with a six-membered ring and to explore possibilities for functionalisation of the triple bond of the newly prepared compounds. The first part of this thesis deals with the synthesis of starting materials containing either an ether group or a malonate residue. The second part deals with the optimisation of conditions and the investigation of the scope of Heck reaction and Sonogashira cross-coupling. The third part describes the attempts to hydrate the triple bond and the last part contains reactions with allylic alcohols. Keywords: synthesis, tandem reaction, natural products, Sonogashira cross-coupling, Heck reaction
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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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Reaction intermediates in homogeneous gold catalysis
Shcherbachenko, Elena ; Roithová, Jana (advisor) ; Matoušová, Eliška (referee)
The presented master thesis is devoted to the investigation of reaction intermediates in homogeneous gold catalysis. Electrospray ionization mass spectrometry (ESI-MS) was used as the primary research technique in this study. Delayed reactant labeling was used as the main method. I have focused mainly on the hydration of 1-phenyl-1-propyne catalyzed by the gold complex [Au(IPr)(MeCN)]BF4 (IPr = 1,3-bis(2,6-di-iso-propylphenyl)imidazol-2- ylidene). I have detected two main intermediates containing one or two gold atoms, respectively (monoaurated and diaurated intermediate). I have obtained rate constants for the degradation of the reaction intermediates and their half-lives. I have derived kinetic isotope effects for the formation and the decomposition of the detected intermediates. I have shown that the kinetics of the degradation of both intermediates is identical, therefore I conclude that hydration of alkynes catalyzed by gold complex [Au(IPr)(MeCN)]BF4 proceeds most probably via neutral monoaurated intermediates. These neutral intermediates are detected by ESI-MS as protonated (monoaurated intermediate) or tagged by a second gold cation (diaurated intermediate). Key words: gold catalysis, reaction intermediates, electrospray ionization, mass spectrometry.
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The synthesis of the derivatives of 2-aryl-4-methylcyclopent-2-en-1-one with potential antifungal activity
Matoušová, Eliška ; Kuneš, Jiří (advisor) ; Hrabálek, Alexandr (referee)
THE SYNTHESIS OF THE DERIVATIVES OF 2-ARYL-4-METHYLCYKLOPENT-2-EN-1-ONE WITH POTENTIAL ANTIFUNGAL ACTIVITY Eliška Matoušová ABSTRACT Several series of compounds with potential antifungal activity related to a national product incrustoporine have been synthesized in last years. The aim of this thesis was to prepare the set of carbanalogues of incrustoporine (2-arylderivatives of 4-methylcyklopent-2-en-1-one) to find whether the substitution of oxygen atom in lactone group by methylen would have any influence on the activity. We found that the antifungal effect of these compounds was very low. It means that the lactone group is necessary for the activity. All the compounds was also tested for cytotoxic activity but they did not display any significant effect. Z O 2-subst.phenyl-4-methylcyklopent-2-en-1-one O O (-) incrustoporine
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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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