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Asymmetric allylic amination of MBH carbamates
Dočekal, Vojtěch ; Veselý, Jan (advisor) ; Kotora, Martin (referee)
Enatiomerically enriched allylic amines are important synthons for the synthesis of biologically active compounds. This diploma thesis is focused on the preparation of these amines via organocatalytic allylic substitution reaction of Morita-Baylis-Hillman (MBH) alcohol derivates. We found an asymmetric decarboxylative reaction of MBH carbamates catalyzed by commercially available dimeric cinchona catalysts. This reaction provides corresponding products in yields up to 98% with enatiomeric excess up to 97%. Our attention was also given to the transformation of allylic amines to the corresponding β-lactams. We found an one-pot reaction consisting of hydrolysis and following lactamization leading to β-lactams. This reaction provides corresponding lactams in isolated yield up to 86% with retained enantioselectivity. Enantiomerically enriched intermediate that is pivotal for the synthesis of Ezetimibe was prepared via this organocatalytic reaction. Possible reaction mechanism of this transformation was proposed based on carried out cross experiment and calculations.
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Development of new pathways for syntheses of sesquiterpenoids
Topolovčan, Nikola ; Kotora, Martin (advisor) ; Dvořák, Dalimil (referee) ; Pour, Milan (referee)
This work consists of four consecutive parts, each dealing with syntheses of structurally diverse compounds. The syntheses were based on the methods within the domain of transition-metal catalyzed and/or mediated reactions with particular emaphasis on the application of organozirconium chemistry. 1. A method for synthesis of tricyclic condensed hydrocarbons possessing 5(6)-7-6(aryl) framework was developed. It is based on reaction of bicyclic zirconacyclopentenes, prepared by oxidative dimerization of enynes on a low-valent zirconocene species (Negishi's reagent), with ortho-halobenzaldehydes in the presence of various additives. The presence of two different centers of reactivity - the sp2 C-Zr and sp3 C-Zr bond - allowed sequential functionalization of each bond. Thanks to its higher nucleophilicity, the sp3 C-Zr bond reacted preferentially with the carbonyl carbon of the aldehyde yielding an oxazirconacycloheptene. The subsequent transmetallation of the remaining sp2 C-Zr bond with CuCl in the presence of other additives (catalysts) enabled an intramolecular cross-coupling reaction with the aryl halide moiety furnishing the desired tricyclic products in reasonable yields. The scope of the reaction with respect to differently functionalized reactants was assessed, as well as its mechanistic...
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Chiral metallocomplex synthons of α-amino acids. Synthesis, physical-chemical properties and applications
Popkov, Alexandr ; Lyčka, Antonín (advisor) ; Kotora, Martin (referee) ; Růžička, Aleš (referee) ; Pour, Milan (referee)
CONCLUSIONS Study of chiral amino acids synthons resulted in: I a deeper understanding of the intramolecular interactions affecting the stereochemistry of alkylation of the metallocomplex o_amino acids synthons. The interactions are a valuable tool for evaluation of the stereochemistry of the complexes; the disclosure of new phenomena in NMR spectroscopy (unexpected long-range couphngs.); 3 synthesis ofthe stereospecific synthon ofglycine; 4 the continuing development of diagnostic tools for the clinical diagnostic of some tumours. 5 the development of an envrronmentally_friendly procedure for multikilogram-scale preparatlon of starting metallocomplex chiral synthons ofo_amino acids.
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Synthesis of Purine - Amino Acid Conjugates
Čapek, Petr ; Hocek, Michal (advisor) ; Kotora, Martin (referee) ; Dvořák, Dalimil (referee) ; Mazal, Ctibor (referee)
4. Conclusions A simple and efficient approach to the synthesis of (purin-6-yl)alanines based on Negishi cross-coupling reactions of 6-iodopurines and iodozinc- alanines applicable to the synthesis of both racemic and optically pure compounds was developed. Though analogous reactions were used before for the synthesis of some simple aryl- or hetarylaranines, this was the first successful use in the functionalization ofprotected nucleobases and nucleosides. A practical method for synthesis of enantiomerically pure (purin-6_ yl)phenylalanines by palladium catalyzeď, copper mediated Stille cross-coupling reactions ofprotected 4-(trimethylstanyl)phenylalanines and 6-iodopurines was developed. This method was used in the synthesis of series of (purin_6_ yl)phenylalanines (bases and nucleosides) varying in substitution in position 9 of purine scaffold and in absolute configuration on o-carbon ofphenylalanine. The shaughnessy method for the Suzuki cross-coupling reactions in aqueous media was further optimized and applied to the single-step synthesis of novel optically pure (adenin-8-yl)phenylalanines and (purine_6_yl)phenyl_ alanines. wide tolerance of this methodology towards variety of functionalities and its applicability to 1abile systems was demonstrated particularly by the very first examples of couplings...
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Synthesis of axially chiral pyridin N-oxides and their application in organocatalysis
Hrdina, Radim ; Kotora, Martin (advisor) ; Černý, Miloslav (referee) ; Dvořák, Dalimil (referee) ; Starý, Ivo (referee)
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Stereoslective addition reaction to ketimines
Franc, Michael ; Veselý, Jan (advisor) ; Kotora, Martin (referee)
This diploma thesis deals with the stereoselective addition reaction of benzothiophenone derivatives to ketimines derived from isatin using bifunctional organocatalysis. The stereoselective addition reaction was optimized to provide the appropriate reaction conditions which were subsequently used to study the scope of the reaction. Keywords Organocatalysis, stereoselective synthesis, bifunctional organocatalysts, ketimines, sulphur heterocykles.
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