|
|
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
|
|
|
Synthesis and reactivity of selected [3]dendralene derivatives
Štemberová, Marie ; Pour, Milan (advisor) ; Matouš, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Marie Štemberová Supervisor: prof. RNDr. Milan Pour, Ph.D. Supervisor - specialist: PharmDr. Zbyněk Brůža, Ph.D. Title of Diploma Thesis: Synthesis and reactivity of chosen derivates of [3]dendralenes This diploma thesis is focused on the preparation of derivates of [3]dendralenes containing electron-withdrawing ester groups. The synthesis is based on a palladium- catalyzed Migita-Stille coupling between stannylated esters and iodinated acrylate which are prepared from methyl-propiolates. Subsequently these dendralenes undergo Dien-transmissive Diels-Alder reaction with electron-deficient dienophile N-phenylmaleimide, resulting in formation of polycyclic structures.
|
|
|
Utilisation of the double bond in the synthesis of new types of molecular photoswitches applicable in biological systems
Bartošová, Aneta ; Ivanová, Lucia (referee) ; Cigánek, Martin (advisor)
This bachelor thesis deals with the synthesis and characterization of new advanced organic molecules with the utilization of the structure motive of the double bond for purposes of application as molecular photoswitches. The theoretical part of the thesis introduces the types of molecules, their characterization and the comparison of fundamental isomers. In the next, section, the mechanisms of isomerization are presented, synthesis via cross-coupling reaction, comparison of advantages and disadvantages of methods and possible application of these molecules in medicine, biological systems and in material chemistry. In the experimental part of the thesis, the multistep synthesis of two final derivatives with an imine bond is described, which can possibly secure the application of these original materials like molecular photoswitches.
|
|
| |
|
|
Novel modified nucleosides with antiviral or cytostatic activity
Tokarenko, Anna ; Hocek, Michal (advisor) ; Rádl, Stanislav (referee) ; Dvořák, Dalimil (referee)
A general and modular synthetic approach to 4-substituted phenyl, 2-substituted pyridin- 5-yl and 5-substituted pyridin-2-yl 2′-C-methyl-C-ribonucleosides as potential anti-HCV agents was developed. Addition of halo(het)aryllithium reagents to benzylated 2-C-methyl-D- ribonolactone gave the corresponding hemiketals, which were subsequently converted to the β-anomeric benzyl-protected bromo(het)aryl-C-nucleosides via either direct reduction (in the case of phenyl derivative) or acetylation followed by reduction of the resulting hemiketal acetates (in the case of pyridyl derivatives). The key halogenated (het)aryl-C-nucleoside intermediates were further transformed by Pd-catalyzed cross-coupling, hydroxylation and amination reactions affording series of protected C-nucleosides with small hydrophilic and hydrophobic substituents. The final protecting group removal was rather problematic, and different debenzylation methods, such as hydrogenation on Pd/C or treatment with BCl3, had to be optimized for each derivative to minimize the formation of side-products. The final C- nucleosides were also converted into their 5′-O-triphosphates, and biological activity screenings revealed that none of the free C-nucleosides possesses any antiviral activity in the HCV replicon assay, and none of their NTPs...
|
|
|
Multiple Output Power Supply Module
For Space Applications
Hrubý, Lukáš
The purpose of this article is to describe design and implementation of multiple output power supply unit. Main goal is to create forward converter with cross-coupling of output lines, which would significantly increase the accuracy of output voltages under different load conditions. As almost every isolated DC-DC converter needs a transformer, there will be a short introduction on how to design and create one utilizing planar technology. For further puproses, this power supply will be designed with respect to requierements which are derived from ESA standards. Whole power unit will be fitted into box designed for mounting on spacecraft.
|
|
| |
|
|
New cross-coupling reactions and C-H activations for synthesis of modified nucleobase analogues
Krömer, Matouš ; Hocek, Michal (advisor) ; Kotora, Martin (referee)
6 Abstract A novel methodology of construction of 6,7-disubstituted 7-deazapurines by serial of orthogonal cross-coupling reactions was developed. The Liebeskind-Srogl reaction was optimized and the reactivity of a few boronic acids was explored. Library of 3×3 disubstuted analogues of deazapurines was synthesized utilizing this method. In the second part of this work, the scope of direct alkylation of purine derivatives was verified. Keywords purine, 7-deazapurine, orthogonal cross-coupling reactions, C-H activations
|
|
|
Synthesis of novel cytostatic deazapurine nucleosides and pronucleotides
Perlíková, Pavla ; Hocek, Michal (advisor) ; Jindřich, Jindřich (referee) ; Hlaváč, Jan (referee)
The synthetic routes to three types of phosphate prodrugs of 6-hetaryl-7-deazapurine ribonucleosides based on palladium-catalyzed cross-coupling reactions have been developed. CycloSal- and phosphoramidate pronucleotides and octadecyl phosphates derived from 6- hetaryl-7-deazapurine ribonucleosides were screened for their in vitro cytostatic activity. It was shown that cytostatic activity of cycloSal phosphates was similar or slightly lower compared to the parent nucleosides. Significant drop of cytostatic activity was observed in phosphoramidate pronucleotides. Octadecyl phosphates were devoid of any cytostatic activity. 6-Hetaryl-7-deazapurine ribonucleosides with bulky groups in position 6 showed very strong and selective inhibition of adenosine kinase from Mycobacterium tuberculosis. 2'-Modified 6-hetaryl-7-deazapurine nucleosides: 2'-O-methylribonucleosides, arabinonucleosides and 2'- deoxy-2'-fluororibonucleosides, were prepared by multistep functional group transformations from a ribonucleoside. The synthesis of 2'-deoxy-2',2'-difluoro-erythro-pentofuranosyl nucleosides was based on a glycosylation of 6-chloro-7-deazapurine with a sugar synthon followed by palladium-catalyzed cross-coupling reaction and deprotection. Despite the low yields and laborious separation of the anomers,...
|
|
|
Development of a general and modular approach to C-nucleosides
Kubelka, Tomáš ; Štefko, Martin ; Bárta, Jan ; Joubert, Nicolas ; Urban, Milan ; Chapuis, Hubert Jean ; Hocek, Michal
Highly efficient and modular approach was developed for the synthesis of various types of new (het)aryl C-nucleosides. This protocol consists of the synthesis of haloaryl-C-nucleoside intermediates, followed by a functional group transformation to introduce various substituents. Using this approach protected 2′-deoxy-C-nucleosides bearing halogenated benzene, pyridine, thiophene, furane and pyrimidine were prepared. These intermediates were then submitted to a wide range of palladium-catalyzed reactions. The same approach was also used for preparation of C-nucleosides bearing ribofuranose moiety. Functional ribofuranosides bearing diverse substituted pyridine and benzene nucleobases were prepared in this way.
|
guest ::
