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Synthesis of new guaiazulene derivatives
Počtová, Žofie ; Kotora, Martin (advisor) ; Smrček, Stanislav (referee)
Synthesis of new guaiazulene derivates (abstract) This bachelor thesis concerns preparation of new guaiazulene derivates. The purpose of this work was to try some already known reactions and some new ones. Acylation of guaiazulene was carried out and was followed by oxidation, decarboxylation, allylation, and Diels-Alder reaction of the prepared guaiazulene derivates. The desired products were obtained in acylation, oxidation, and allylation reactions. Characterization of the prepared substances was performed by using NMR, IR or MS techniques.
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Synthesis and Use of Transition Metal Complexes with Helical Ligands
Žádný, Jaroslav ; Vojtíšek, Pavel (advisor) ; Kotora, Martin (referee) ; Růžička, Aleš (referee)
The Thesis describes our successful endeavour to develop asymmetric synthesis of functionalized 2H-pyran or 2,7-dihydrooxepine helicene-like compounds in an optically pure form. These helicene surrogates were fully characterized and their use in enantioselective catalysis as chiral ligands, organocatalysts or chiral modifiers was explored. A general method for the preparation of optically pure [5]- and [6]heterohelicenes by asymmetric synthesis is based on highly diastereoselective [2+2+2] cycloisomerization of centrally chiral triynes mediated/catalyzed by transition metal complexes. Stereochemical outcome of the cyclization process is controlled by 1,3-allylic-type strain. This new methodology is highly versatile providing an easy access to chiral ligands, organocatalysts or modifiers in a nonracemic form. Optically pure 2,7-dihydrooxepine [5]helicene-like phosphite ligands were explored in enantioselective allylic amination under catalysis by iridium(I) complexes to reach up to 82% ee. An organocatalysts represented by the optically pure 2H-pyran [5]helicene-like DMAP analogue was synthesized and applied to kinetic resolution of racemic sulfoximines. Finally, various functionalized derivatives of helicenes and helicene-like compounds (azahelicenes, DMAP analogues, (thio)urea derivatives) were...
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Enantioselective synthesis of spiro compounds
Urban, Michal ; Veselý, Jan (advisor) ; Kotora, Martin (referee)
This thesis deals with the preparation of enantiomerically and diastereomerically pure spirocompounds using asymmetric organocatalysis. The first part is focused on the enantioselective synthesis of spirocompounds by organocatalytic reaction of α,β-unsaturated aldehydes with sulfur heterocyclic compounds catalysed with secondary amines. It is a domino Michael/Michael/aldol reaction using iminium and enamine activation. The second part is focused on the subsequent transformation of the prepared spirocompounds.
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Total Synthesis of (-) - Methoxyestrone
Betík, Robert ; Kotora, Martin (advisor) ; Dvořák, Dalimil (referee) ; Jahn, Ullrich (referee)
English Abstract The new diastereoselective synthesis of estrone precursor and enantioselective synthesis of (-)-methoxyestrone are described in this work. The diastereoselective synthesis was based on 2 Bu2ZrCp2 mediated reactions followed by Pauson-Khand cyclocarbonylation. The sequence of reactions yielded 16-keto-17-methylestratetraene, compound with tetracyclic steroid framework, with excellent diastereoselectivity. Synthesis was finished with chemoselective reduction of the keto group in 16-keto-17-methylestratetraene to furnish 17- methylestratetraene, which is known precursor of estrone. The enantioselective synthesis was based on a conjugate addition of vinylmagnesium bromide to aldimine formed from 1-formyl- 3,4-dihydro-6-methoxynaphthalene and (L)-t-leucine t-butyl ester, which afforded crucial chiral intermediate 1-formyl-3,4-dihydro-6-methoxy-2-vinyl-naphthalene with very high ee > 98 %. Further transformations led to the construction of alkyl side chain containing triple bond and finally, the Pauson-Khand cyclocarbonylation followed by chemoselective reduction of carbonyl group gave estrone precursor, which was converted to (-)- methoxyestrone according known procedure.
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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
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Synthesis of C-organyldeoxyriboside and C-organylriboside derivatives mediated by catalysis of transition metal complexes
Bobula, Tomáš ; Kotora, Martin (advisor) ; Dvořák, Dalimil (referee) ; Veselý, Jan (referee)
The aim of my project was to examine reactivity of the triple bonds present in both C- alkynylriboside and C-alkynyldeoxyriboside structures by means of an organocatalysis with the transition metal complexes (Pd, Rh, Ru, Ir, Fe, Ni). I hereby paid attention to the development of an alternative synthetic approach leading to substituted derivatives of alkynylferrocene. The applied synthetic methodologies were based on [2+2+2] cyclotrimerization, Sonogashira cross-coupling reaction and alkyne cross-metathesis. The main targets were C-arylribosides, C-aryl-/C-hetarylalkynyldeoxyribosides and aryl- /alkylethynylferrocenes. My project can be divided into three following sections: The first part was focused on the synthesis of C-arylribosides by [2+2+2] cyclotrimerization. It is powerful reaction where benzene ring is formed in one reaction step from ethynylribofuranose and -diyne. The obtained products represent more stable C-ribosides in comparison to naturally occuring types of pyrimidine nucleosides. The second part of my project was similarly pointed to the C-nucleoside preparation. In this case deoxyribofuranose derivatives were prepared by a modified Sonogashira cross- coupling reaction. The optimization of the reaction conditions enabled to assemble aryl-, hetaryl- and...
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Enantioselective reactions catalyzed by chiral heterocyclic compounds
Vlašaná, Klára ; Kotora, Martin (advisor) ; Starý, Ivo (referee) ; Sedlák, Miloš (referee)
Novel bis(tetrahydroisoquinoline) N,N'-dioxides 1,2 belong to the group of compounds with axial chirality that act as a Lewis base. These properties make them useful chiral catalysts in reactions such as allylation, opening of epoxides, etc. that exhibit high enantioselectivity. The prepared chiral bis(tetrahydroisoquinoline) N,N'-dioxides (R,Rax,R)-1, (R,Sax,R)-1, (Rax,R)-2 a (Sax,R)-2 were tested as catalysts in enantioselective allylation of variously substituted α,β−unsaturated aldehydes and dienals with allyltrichlorosilane (Scheme 1). All the catalysts exhibited high catalytic activity as well as high asymmetric induction (up to 96% for α,β- unsaturated aldehydes;1 up to 98 % for dienals). Appropriate choice of solvent as a reaction medium3,4 and substitution in α-position in aldehydes were the crucial factors for the successful course of the reaction. The catalytic activity of (R,Rax,R)-1 and (R,Sax,R)-1 was also tested in asymmetric opening of meso-epoxides with tetrachlorosilane (ee up to 69 %) (Scheme 2). N N O O O O 1 N N O O O 2 Scheme 1 Scheme 2 1) Vlašaná, K.; Hrdina, R.; Valterová, I.; Kotora, M. Eur. J. Org. Chem. 2010, 7040. 2) Kadlčíková, A.; Hrdina, R.; Valterová, I.; Kotora, M. Adv. Synth. Catal. 2009, 351,1279. 3) Hrdina, R.; Opekar, F.; Roithová, J.; Kotora, M. Chem. Commun....
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Use of Coupling Reactions in the Synthesis of Potentially Biologically Active Compounds.
Hessler, Filip ; Kotora, Martin (advisor) ; Moravcová, Jitka (referee) ; Pour, Milan (referee)
This work consists of three parts, each dealing with the synthesis of different biologically active compound, using reactions mediated by transition metals. 1. Ferrocene conjugates with various types of natural or biologically active compounds have been studied intensively for their new interesting properties compared to the model compounds. It was decided to synthesize a new steroid containing ferrocene - ferrocenestrone, planned with regard to its possible activity against breast cancer cells. Although several conjugates of steroids with ferrocene have been prepared, the cyclopentadienyl ring has not been the integral part of the steroid skeleton in any of them. Ferrocenestrone, an analog of estrone, however contains ferrocene in place of the aromatic A-ring. The approach to the ferrocene-steroid framework construction was based on transition metal mediated reactions starting from a suitably substituted chiral ferrocene. The methods used were: zirconocene-mediated oxidative additions with successive alkylation sequences, palladium- catalyzed cross-coupling reactions, ruthenium-catalyzed skeletal rearrangements (enyne metathesis), palladium and iridium catalyzed hydrogenations etc. Also selective oxidation and subsequent borane reduction was used for the final change of skeletal configuration....
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