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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 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 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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Use of alkenylboronic acids in the tandem cyclisation/Suzuki cross-coupling
Klanicová, Kristýna ; Matoušová, Eliška (advisor) ; Míšek, Jiří (referee)
This thesis deals with the synthesis of polycyclic compounds using tandem cyclisation/Suzuki cross-coupling, by modification of the method developed by our research group. This thesis mainly investigates the scope of the tandem reaction with aliphatic boronic acids or their esters. The products of the palladium catalyzed reaction then underwent electrocyclization to form an aromatic ring. The polycyclic skeleton, containing the aromatic core, is found in a considerable amount of natural substances with biological activity. The structure of the compounds prepared herein is similar to miltiorin D or commiphorane A.
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Synthesis of all-carbon quaternary centres
Orlovská, Ľubica ; Matoušová, Eliška (advisor) ; Hájíček, Josef (referee)
In this diploma Thesis I dealt with the synthesis of nitrogen compounds that contain quaternary carbon centres and their structure resembles natural substances, specifically alkaloids from the Amaryllidaceae family. Halocarbocyclization or Heck reaction was planned as a key step of the synthesis, which should lead to the formation of quaternary carbon centres. First, starting nitriles and esters with five- and six-membered rings were prepared. Subsequently, the method for the preparation of a stable bicyclic ketone with a five-membered ring from an ester was optimized. The next part of the Thesis is devoted to the synthesis of a substrate for the Heck reaction from the prepared ketone, which was then used for the preparation of the alkaloid skeleton with a quaternary carbon centre, unfortunately without success so far. In the last part of the work, a bicyclic ketone with a six-membered ring, from which it is possible to prepare a substrate for the Heck reaction in several steps already used for five-membered substances, was prepared from the nitrile by carbopalladation. Key words: synthesis, quaternary carbon centres, Heck reaction, halocarbocyclisation, Amaryllidaceae alkaloids
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