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Enantioselective allylation of thiophene-2-carbaldehyde
Motloch, Petr ; Kotora, Martin (advisor) ; Veselý, Jan (referee)
The first part of the bachelor thesis deals with enantioselective allylation of thiophene-2- carbaldehyde to the corresponding chiral homoallylic alcohol by using chiral Lewis bases as catalysts. The highest asymmetric induction achieved was 97 % ee. The second part concerns application of the prepared chiral homoallylic alcohol as the crucial intermediate for synthesis of antidepressant (S)-duloxetine. Key words enantioselective, allylation, Lewis base, thiophene-2-carbaldehyde, duloxetine
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Synthesis of the C15-C20 tiacumicin fragment
Havlíček, Vojtěch
In the diploma thesis, a method for preparation of the unsaturated C15-C20 tiacumicin fragment was developed. Tiacumicin is classified as a macrolidone antibiotic. Although three syntheses of tiacumicin have been recently published, this study has aimed to develop a novel pathway for its preparation utilizing catalytic reactions instead of stoichiometric ones. In the second part, an enantioselective allylation of (E)-3-jod-2-methylpropenal has been developed applying catalysis by a series of N,N'-dioxide catalysts. The asymmetric induction achieved in the allylation was up to 99% ee. This procedure allows relatively simple, straightforward and efficient preparation of wide range of natural products. Keywords tiacumicin, asymmetric synthesis, allylation, catalysis, chiral Lewis bases, organocatalysis
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Synthesis of the C15-C20 tiacumicin fragment
Havlíček, Vojtěch
In the diploma thesis, a method for preparation of the unsaturated C15-C20 tiacumicin fragment was developed. Tiacumicin is classified as a macrolidone antibiotic. Although three syntheses of tiacumicin have been recently published, this study has aimed to develop a novel pathway for its preparation utilizing catalytic reactions instead of stoichiometric ones. In the second part, an enantioselective allylation of (E)-3-jod-2-methylpropenal has been developed applying catalysis by a series of N,N'-dioxide catalysts. The asymmetric induction achieved in the allylation was up to 99% ee. This procedure allows relatively simple, straightforward and efficient preparation of wide range of natural products. Keywords tiacumicin, asymmetric synthesis, allylation, catalysis, chiral Lewis bases, organocatalysis
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Application of enantioselective allylation for synthesis of compounds isolated from Streptomyces gramineus
Morávková, Terézia ; Kotora, Martin (advisor) ; Matoušová, Eliška (referee)
E-492, actinofuranone A, and JBIR-108 are natural compounds isolated from actinobacteria Streptomyces genus and can lead to the development of new pharmaceuticals as they have some biological interesting activities. Although the synthesis of these actinofuranones has been already published, this work brings new methods for the preparation of their fragments. The key step of the synthesis is enantioselective crotylboration of an aldehyde catalyzed by a chiral Brønsted acid and by which two centres of chirality are introduced in one step. The other crucial steps of the synthesis are composed of Ru-catalyzed alkene-alkene cross-metathesis and Pd- catalyzed Suzuki cross-coupling. Keywords: natural compound, enantioselective syntheses, crotylation, catalysis, actinofuranone fragment
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Enantioselective synthesis of an actinofuranone fragment
Morávková, Terézia ; Kotora, Martin (advisor) ; Machara, Aleš (referee)
This bachelor thesis is focused on the new preparation procedure of the unsaturated actinofuranone fragment JBIR-108 which was isolated from actinobacteria Streptomyces gramineu. This exotoxin appears to be cytotoxic to some types of cancer cells. Although the synthesis of this actinofuranone has already been published by the group of T. Doi,1 this work brings a new method for the preparation of fragment C7-C18. The key steps for this synthesis are crotylation reaction, cross metathesis and Suzuki cross-coupling. Key words: crotylation, natural compound, actinofuranone fragment, Suzuki cross-coupling, asymmetric synthesis
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Synthesis of the C15-C20 tiacumicin fragment
Havlíček, Vojtěch ; Kotora, Martin (advisor) ; Veselý, Jan (referee)
In the diploma thesis, a method for preparation of the unsaturated C15-C20 tiacumicin fragment was developed. Tiacumicin is classified as a macrolidone antibiotic. Although three syntheses of tiacumicin have been recently published, this study has aimed to develop a novel pathway for its preparation utilizing catalytic reactions instead of stoichiometric ones. In the second part, an enantioselective allylation of (E)-3-jod-2-methylpropenal has been developed applying catalysis by a series of N,N'-dioxide catalysts. The asymmetric induction achieved in the allylation was up to 99% ee. This procedure allows relatively simple, straightforward and efficient preparation of wide range of natural products. Keywords tiacumicin, asymmetric synthesis, allylation, catalysis, chiral Lewis bases, organocatalysis
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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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Enantioselective allylation of thiophene-2-carbaldehyde
Motloch, Petr ; Kotora, Martin (advisor) ; Veselý, Jan (referee)
The first part of the bachelor thesis deals with enantioselective allylation of thiophene-2- carbaldehyde to the corresponding chiral homoallylic alcohol by using chiral Lewis bases as catalysts. The highest asymmetric induction achieved was 97 % ee. The second part concerns application of the prepared chiral homoallylic alcohol as the crucial intermediate for synthesis of antidepressant (S)-duloxetine. Key words enantioselective, allylation, Lewis base, thiophene-2-carbaldehyde, duloxetine
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