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Synthesis of new derivatives of combretastatine
Brůža, Zbyněk ; Pour, Milan (advisor) ; Macháček, Miloš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Zbyněk Brůža Consultant: Prof.RNDr. Milan Pour, Ph.D. Title of Thesis: Synthesis of new derivatives of combretastatin The aim of this work was the synthesis of novel structural analogues of combretastatin, including further structural modifications. Synthetic modifications might improve biological activity as well as pharmacokinetics of the compounds. Two 3,4-diaryl-2,5-dihydrofuran-2- ones were synthesized. The sequence comprises well-known reactions starting from α-halogenated acetophenones, which are converted to esters of phenylacetic acids. The esters are then cyclized to the final 2,5-dihydrofuran-2-ones analogues under basic conditions. The title compounds were screened for their antibacterial, antifungal and cytotoxic activity. Because of the difficulties especially in the cyclization step, we have tried to develop an alternative synthetic procedure based on Pd-catalysed cross-coupling reactions of different aryl halides with heterocycles as bridging structural fragments.
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Department of Organic and Bioorganic Chemistry
Brůža, Zbyněk ; Pour, Milan (advisor) ; Tobrman, Tomáš (referee) ; Starý, Ivo (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Organic and Bioorganic Chemistry Candidate Mgr. Zbyněk Brůža Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis and application of polysubstituted pyranones This Thesis deals with the development of the isomerization of 5-alkyliden-5,6-dihydro-2H- pyran-2-ones to 6-alkyl-5-methylidene-5,6-dihydro-2H-pyran-2-ones. This process is an unusual version of the intramolecular Tsuji-Trost reaction, the products of which are seemingly thermodynamically unfavourable. The methodology developed through the optimization of the reaction conditions tolerated a broad range of functional groups. Quantum chemistry calculations identified the formation of the pyramidal η2-complex as the key step of the reaction, which made the formation of the final products possible.
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Department of Organic and Bioorganic Chemistry
Brůža, Zbyněk ; Pour, Milan (advisor) ; Tobrman, Tomáš (referee) ; Starý, Ivo (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Organic and Bioorganic Chemistry Candidate Mgr. Zbyněk Brůža Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis and application of polysubstituted pyranones This Thesis deals with the development of the isomerization of 5-alkyliden-5,6-dihydro-2H- pyran-2-ones to 6-alkyl-5-methylidene-5,6-dihydro-2H-pyran-2-ones. This process is an unusual version of the intramolecular Tsuji-Trost reaction, the products of which are seemingly thermodynamically unfavourable. The methodology developed through the optimization of the reaction conditions tolerated a broad range of functional groups. Quantum chemistry calculations identified the formation of the pyramidal η2-complex as the key step of the reaction, which made the formation of the final products possible.
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Department of Organic and Bioorganic Chemistry
Brůža, Zbyněk ; Pour, Milan (advisor) ; Tobrman, Tomáš (referee) ; Starý, Ivo (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Organic and Bioorganic Chemistry Candidate Mgr. Zbyněk Brůža Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis and application of polysubstituted pyranones This Thesis deals with the development of the isomerization of 5-alkyliden-5,6-dihydro-2H- pyran-2-ones to 6-alkyl-5-methylidene-5,6-dihydro-2H-pyran-2-ones. This process is an unusual version of the intramolecular Tsuji-Trost reaction, the products of which are seemingly thermodynamically unfavourable. The methodology developed through the optimization of the reaction conditions tolerated a broad range of functional groups. Quantum chemistry calculations identified the formation of the pyramidal η2-complex as the key step of the reaction, which made the formation of the final products possible.
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Synthesis of new derivatives of combretastatine
Brůža, Zbyněk ; Pour, Milan (advisor) ; Macháček, Miloš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Zbyněk Brůža Consultant: Prof.RNDr. Milan Pour, Ph.D. Title of Thesis: Synthesis of new derivatives of combretastatin The aim of this work was the synthesis of novel structural analogues of combretastatin, including further structural modifications. Synthetic modifications might improve biological activity as well as pharmacokinetics of the compounds. Two 3,4-diaryl-2,5-dihydrofuran-2- ones were synthesized. The sequence comprises well-known reactions starting from α-halogenated acetophenones, which are converted to esters of phenylacetic acids. The esters are then cyclized to the final 2,5-dihydrofuran-2-ones analogues under basic conditions. The title compounds were screened for their antibacterial, antifungal and cytotoxic activity. Because of the difficulties especially in the cyclization step, we have tried to develop an alternative synthetic procedure based on Pd-catalysed cross-coupling reactions of different aryl halides with heterocycles as bridging structural fragments.
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