This diploma thesis deals with the synthesis of chiral five-membered carbacyclic molecules via iminium-enamine activation using chiral secondary amines. The first part of thi diploma thesis describes the synthesis of starting materials for domino Michael addition/α-alkylation reaction, i.e. the synthesis of α,β-unsaturated aldehydes and 1-bromo-3-nitropropane. The second part of this diploma thesis is focused on the optimization of reaction conditions and the application of the domino Michael addition/α-alkylation reaction, that leads to the formation of cyclopentancarbaldehydes with contiguous stereogenic centres. Key words Asymmetric synthesis, organocatalysis, domino reaction, Michael addition, cyclopentanes.

This study focus on synthesis of novel compounds as potential agents for the therapy of mycoses. The following four novel compounds were synthesized: 1-(4-(octylsulfanyl)-3-(trifluoromethyl)phenyl)guanidine, 1,1-dimethyl-3-(4-(octylsulfanyl)-3-(trifluoromethyl)phenyl)guanidine, 1-(4-(decylsulfanyl)-3-(trifluoromethyl)phenylguanidine, 3-(4-(decylsulfanyl)-3-(trifluoromethyl)phenyl-1,1-dimethylguanidine. All intermediary and final crystalline products formed were thoroughly purified and characterized by Thin Layer Chromatography (TLC) and Melting points. Structures were elucidated on the basis of Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. 1- (4-(octylsulfanyl)-3-(trifluoromethyl)phenyl)guanidine was evaluated for in vitro antimicrobial activity on different fungal and bacterial strains.

Pathological fungi carry the ability to cause serious medical problems and moreover cause various diseases. Drug therapy and new active compounds against these medical problems are still being researched. The long-term objective is to uncover the active compounds at the Faculty of Pharmacy, Charles University. In our study, we synthesized 3-(4-bromophenyl)-1,1-diethylguanidine, and 2 novel compounds: 3-(4- dodecylsulfanylphenyl)-1,1-diethylguanidine and 3-(3-bromophenyl)-1,1- diethylguanidine. We also studied the oxidation of 1-(4- tetradecylsulfanylphenyl)guanidinium nitrate, thus, making it the third novel compound 1-(4-tetradecylsulfonylphenyl)guanidinium nitrate we synthesized.

The PhD thesis concerns the synthesis of novel zeolite materials, investigation of their properties and their possible use in catalytic application. The work was focused on the two- dimensional zeolites. The thesis was worked out at the Department of Synthesis and Catalysis at J. Heyrovský Institute of Physical Chemistry, AS CR. Germanosilicate UTL (Si/Ge molar ratio 4.0-6.5) was found to undergo unique structural changes in the neutral or acid environment leading to transformation of its three-dimensional framework into two-dimensional layered material denoted IPC-1P. The UTL degradation, so called top-down synthesis, was enabled due to a presence of double-four-units (D4Rs), which can be seen as supporting units/pillars between the rigid layers. The preferential location of Ge in D4Rs makes the units an ideal target for their selective degradation. The interlayer space in lamellar IPC-1P was modified by swelling with long-organic chain surfactant (material IPC-1SW). To keep the interlayer space permanently expanded (up to 3.3 nm) the silica amorphous pillars were subsequently introduced (material IPC-1PI). The integrity of the layers and their preserved UTL character was confirmed in all members of IPC-1 family by HRTEM and electron diffraction measuring. The layers of IPC-1P were condensed back...

Charles university in Prague Faculty of Pharmacy in Hradec Králové Department of Anorganic and Organic Chemistry Candidate: Ondřej Vidrna Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs IX. The increasing incidence of diseases caused by fungal and mycotic pathogens, many of which acquire resistance to available antifungal substances, causes the need for a search for new molecules inhibiting their growth. The worldwide research is focused on substances derived from guanidine which were found to be potentially active against many strains of fungi and bacteria. Faculty of Pharmacy in Hradec Králové has been researching these substances for many years. The aim is to get the most active compounds from the group of substituted arylguanidines and find a structure-activity relationships effect of these substances. In this study the seven previously undescribed molecules were synthesized: 1-(4- methyl-2-octylsulfanyl)phenylguanidinium nitrate, 1-(4-methyl-2-dodecylsulfanyl) phenylguanidinium nitrate, 1-(4-methyl-2-dodecylsulfanyl)phenyl-3,3-dimethylguanidine, octyl-(4-methyl-2-nitrophenyl)sulfide, 5-methyl-2-(octylsulfanyl)aniline, dodecyl-(4-methyl-2- nitrophenyl)sulfide and 5-methyl-2-(dodecylsulfanyl)aniline. Three of them were...

Insulin receptor (IR) exists in two isoforms (IR-A and IR-B), which differ in the tissue distribution and probably also in their function, i.e. in their response to insulin binding. It is supposed that IR-A activates mainly mitogenic processes and that IR-B triggers mainly metabolic effects resulting in the uptake of glucose by muscle and fat cells. Insulin can also weakly bind to the receptor for IGF-1 (IGF-1R), a growth factor involved in the regulation of growth and development. Insulin derivatives selectively binding only to one of the receptors would be interesting for the study of the receptors but also potentially for the treatment of diseases such as diabetes or cancer. Here we used our experience in the structure-activity studies of insulin for the design, synthesis and biological characterization of 4 new insulin derivatives in order to modify their selectivity towards the individual receptors. We systematically modified insulin by amidation of the C-terminus of its B-chain or by prolongation of the B-chain by 1-3 carboxyamidated glycine residues. Binding affinities of all new analogues for IR-A and IR-B were determined and for some of the analogues binding affinities for IGF-1R as well. Finally, abilities of analogues to activate autophosphorylation of intracellular subunits of IR-A and...

The aim of this thesis is introduce readers to the basics of digital frequency synthesis and design of direct digital synthesizer with circuit AD9951 by Analog Devices. The device will be controlled from a PC via RS232. The device will work with internal oscillator, with the ability to connect an external frequency standard.

2,2'-Bipyridines and their appropriate N,N'-dioxides form a significant class of heteroaromatic compounds, which has found application in various fields of chemistry and predominantly in asymmetric catalysis. One of the most powerful methods for their synthesis is cocyclotrimerization of alkynes with nitriles. A new variant of cyclotrimerization reaction - cocyclotrimerization of halodiynes with nitriles, which results in the formation of 2- and 3-halopyridines, has been developed. The reaction was studied on a wide range of substrates providing the pyridine products in good isolated yields. Formation of an unexpected product of halogen exchange reaction was observed during the course of the study and its origin was elucidated by experimental studies. The prepared 2-halopyridines were used as starting materials for syntheses of new chiral 2,2'-bipyridine ligands. The crucial step of their synthesis turned out to be the reductive dimerization of 2-halopyridines to the corresponding 2,2'-bipyridines. Application of the formed bipyridine ligands was then tested in various metal-catalyzed asymmetric reactions, namely Mukaiyama aldol reaction, hydroxymethylation, conjugate addition, C-H activation of indole and desymmetrization of meso-epoxides, in which one of the bipyridine ligands showed...

With regard to a fast development in the field of fluoroorganic chemisty, the intention of this diploma thesis is focused to utilize of organocatalysis by secondary amines as catalysts for preparation enantiomerically pure compounds containing fluorine atom in its structure. The preparation of these subsances is realized by way of nucleofilic addition to α,β- unsaturated aldehydes using suitable fluorine containing nuclephilic agent 1-(fluoronitromethylsulphonyl)benzene, to get appropriate 1,4-adduct.

The importance of the searching for novel antimycobacterial active agents is continually increasing with growing mycobacterial resistance to currently used drugs. However, the resistance-related problems are also associated with other bacteria and fungi. The systematic modification of compounds with a known antimicrobial activity represents one of the possible approaches to overcome this problem. Sulphonamide derivatives may be considered to be such a kind of compounds. That is why we synthesized various sulphathiazole derivatives. Amides were obtained by the reaction of sulphathiazole with appropriate acyl chlorides, substituted ureas from corresponding isocyanates. These ureas were cyclized via oxalyl chloride to form substituted 2,4,5-trioxoimidazolidines. Among derivatives evaluated for their antimycobacterial action, 4-(3- phenethylureido)-N-(thiazol-2-yl)benzenesulphonamide showed the highest activity. Its minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis My 331/88 (4 µmol/l) were superior to those obtained for sulphathiazole. In the case of nontuberculous mycobacteria (M. avium My 330/88, M. kansasii My 235/88 and M. kansasii My 6509/96), their activities were comparable (≥ 2 µmol/l). Amides showed also a significant antimycobacterial activity, especially against M....