National Repository of Grey Literature 13 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
Nucleophile-Assisted Gold(I)-Catalyzed Cyclizations of Enynes
Kadaník, Michal ; Pour, Milan (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Michal Kadaník Supervisor: Prof. RNDr. Milan Pour, Ph.D. Title of thesis: Nucleophile-Assisted Gold(I)-Catalyzed Cyclizations of Enynes This work is focused on gold(I)-catalyzed cyclizations of substituted enyne in the presence of a nucleophile. The screening of various gold catalysts, silver co-catalysts, solvents and nucleophiles was performed. We achieved the formation of substituted tetrahydropyridine with excellent diastereoselectivity by optimization of the reaction conditions. To extend our methology, the second part deals with the gold(I)-catalyzed cyclization of the enyne with chiral center. The cyclization was found to be enantioselective. Keywords: gold catalysis, tetrahydropyridines, hemiaminals, hemiaminalethers
Synthesis of new types of succinimides as a potential adjuvant
Božiková, Slavomíra ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Student: Slavomíra Božiková Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Consultant: RNDr. Dávid Maliňák, PhD Title of Diploma Thesis: Synthesis of new types of succinimides as a potential adjuvant Adjuvants represent a big group of the compounds used for the increased immune response to vaccines. This whole concept of these helper substances is more than 80 years old. The first finding that started the research of more substances was the alternative system of the aluminium salt. Important group of adjuvants are substances, which activate the immunity system to increased reaction after stimulation of toll-like receptors (TLRs) that are present in the human body. These receptors are considered as one of the most important immunity molecules. The best examined receptors of this group is the TLR4 receptor that binds various ligands. The most important ligands are the lipopolysaccharide of Gram-negative bacteria. Mechanisms of the interaction of these ligands with TLR4 are being examined recently. In my thesis I focused on the TLR4 receptors and on the synthesis of new molecules of the succinimide type, which eventually can stimulate these receptors and be potential adjuvants.
Use of lactones in acylceramide synthesis
Moravčík, Štefan ; Opálka, Lukáš (advisor) ; Roh, Jaroslav (referee)
6 Abstract Acylceramides, subgroup of ceramides with ultralong chains, are essential component of extracellular lipid matrix in the uppermost skin layer, stratum corneum. They have crucial role in mammalian survival on dry land. Deeper understanding of their function in physiology of pathophysiology of the skin and their therapeutic potential are hampered by their limited availability. Analysis of the skin surface lipids of the ass (E. asinus) has shown, that these lipids contain up to 56% of unbranched ω-lactones (equolides), from which 51.2% is mono- unsaturated dotriacontanolide and 41.3% is mono-unsaturated triacontanolide. Carbon chain length of these lactones match the most common length of carbon chain in acylceramides (30 and 32 carbon atoms) therefore they could be used in their total synthesis. Aim of this thesis was to isolate mono-unsaturated ω-lactone with 32 carbon chain (dotriacontanolide) from the mixture of donkey skin surface lipids, followed by hydrogenation and transformation to the suitable precursor (succinmidyl ester) in order to find the easiest synthetic path in its conversion to acylceramides. We have tried many synthetic pathways. From direct aminolysis of lactone, through reaction with N-hydroxysuccinimide in various reaction conditions to opening of the lactone to the potassium...
Synthesis of phosphoramidate prodrugs "ProTides" as novel potential therapeutic agents for the treatment of congenital disorders of glycosylation and mitochondrial DNA depletion syndrome
Sedláková, Jana ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic And Bioorganic Chemistry Candidate: Jana Sedláková Supervisors: Dr. Fabrizio Pertusati doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: Synthesis of phosphoramidate prodrugs "ProTides" as novel potential therapeutic agents for the treatment of congenital disorders of glycosylation and mitochondrial DNA depletion syndrome At the present time, no effective treatment is available neither for the most of the congenital disorders of glycosylation (CDGs) nor the mitochondrial DNA depletion syndrome (MDS). Regarding the CDG therapy, D-mannose-1-phosphate (Man-1-P) offers considerable pharmacological potential to improve the pathological patterns in patients affected by phosphomannomutase 2 deficiency (PMM2-CDG), similarly as N-acetyl-D-mannosamine-6-phosphate (ManNAc-6-P) in case of GNE myopathy (GNEM). Administration of selected deoxyribonucleotides was proposed as a potential pharmacological strategy for the treatment of MDS. Unfortunately, the problematic membrane penetration of such polar molecules reduces their effect and limits their clinical application. Hydrophobic, membrane permeable derivatives of the sugar monophosphates and nucleotides, might represent more efficient potential therapeutics for CDGs and...
Synthesis of phosphoramidate prodrugs "ProTides" as novel potential therapeutic agents for the treatment of congenital disorders of glycosylation and mitochondrial DNA depletion syndrome
Sedláková, Jana ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic And Bioorganic Chemistry Candidate: Jana Sedláková Supervisors: Dr. Fabrizio Pertusati doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: Synthesis of phosphoramidate prodrugs "ProTides" as novel potential therapeutic agents for the treatment of congenital disorders of glycosylation and mitochondrial DNA depletion syndrome At the present time, no effective treatment is available neither for the most of the congenital disorders of glycosylation (CDGs) nor the mitochondrial DNA depletion syndrome (MDS). Regarding the CDG therapy, D-mannose-1-phosphate (Man-1-P) offers considerable pharmacological potential to improve the pathological patterns in patients affected by phosphomannomutase 2 deficiency (PMM2-CDG), similarly as N-acetyl-D-mannosamine-6-phosphate (ManNAc-6-P) in case of GNE myopathy (GNEM). Administration of selected deoxyribonucleotides was proposed as a potential pharmacological strategy for the treatment of MDS. Unfortunately, the problematic membrane penetration of such polar molecules reduces their effect and limits their clinical application. Hydrophobic, membrane permeable derivatives of the sugar monophosphates and nucleotides, might represent more efficient potential therapeutics for CDGs and...
Optimization of the synthesis of 32-hydroxydotriacontanoic acid
Sommerová, Veronika ; Opálka, Lukáš (advisor) ; Roh, Jaroslav (referee)
1 Abstract Acylceramides belong to the subgroup of ultralong chain ceramides. They are essential components of the extracellular lipid matrix of stratum corneum, where they play a crucial role in proper function of skin barrier (they help preventing the excessive water loss and penetration of exogenous substances and pathogens to the organism). The 32-hydroxydotriacontanoic acid is one of the fatty acids forming the backbone of all the acylceramides. In the molecule of acylceramide, the carboxyl group of this acid is bound to a primary amino group of the sphingoid base and the ω-hydroxy group is esterified with linoleic acid. In the stratum corneum, 32-hydroxydotriacontanoic acid may remain as a part of free acylceramides or it can be covalently linked to the surface of corneocytes and form the "first lamela", which then serves as a basis for the orientation of other lipids in the matrix. The recent literature describes the synthesis of 32-hydroxydotriacontanoic acid but only with relatively small overall yields. The most problematic part of the synthesis seems to be the connection of two shorter fragments leading to the ultralong chain. The main aim of this research project was to optimalise the reaction conditions to increase the yield of formation of the utralong acid, focusing on the most complicated...
Synthesis and study of 1-O-acylceramides
Jon, Vojtěch ; Vávrová, Kateřina (advisor) ; Opálka, Lukáš (referee)
The extracellular matrix of the uppermost layer of the skin, the stratum corneum (SC), consists of ceramides (Cer), cholesterol (Chol), free fatty acids (FFA) and cholesteryl sulfate (CholS). Cer play an important role in the correct barrier function of mammalian epidermis. A new type of sphingolipids, i.e., 1-O-acyl-Cer, have been found in human SC very recently; however, their role in the SC is unknown. These Cer species contain sphingosine (S) that is N- acylated with non-hydroxylated or α- hydroxylated fatty acid, and moreover, hydroxyl group at C1 in sphingosine is esterified by an additional fatty acid (lignoceric acid, C24 or palmitic acid, C16). Because 1-O-acyl-Cer are not commercially available, we aimed to synthesize physiological 1-O-acyl Cer, i.e., Cer-24NS16, Cer-16NS16 and Cer-24AS16. Moreover, we aimed to study their behaviour on permeability and microstructure of model skin lipid membranes. The 1-O-acyl-Cer were synthesized by an acylation of Cer-NS16 or Cer-AS16 with palmitic or lignoceric acid using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and 4- dimethylaminopyridine. Cer-AS16 was prepared by α-bromination of palmitic acid, substitution of bromine by hydroxyl and N-acylation of sphingosine by the prepared acid in the presence N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide...
Synthesis of novel acetylcholinesterase reactivators of isoquinolinic type
Hozová, Miroslava ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Student: Miroslava Hozová Supervisor: PharmDr. Jaroslav Roh, Ph.D. Consultant: RNDr. Dávid Maliňák, Ph.D. Title of Diploma Thesis: Synthesis of novel acetylcholinesterase reactivators of isoquinolinic type Organophosphates are worldwide the most common cause of poisoning, whether in the field of agriculture, attempted suicide, accidental contact or abuse as organophosphorus nerve agents. They can be absorbed by all paths - inhaled, ingest or by transdermal penetration. For over 50 years the only causal antidotes on the market have been acetylcholinesterase reactivators. However, bioavailability is inadequate, therapy is ineffective, and there is no broad-spectrum reactivator able to efficiently restore AChE activity after intoxication by different types of organophosphates. All available reactivators are charged oximes with one or two pyridinium rings. These are pralidoxime, methoxime, trimedoxime, obidoxime, HI-6 and Hlö-7. Effective structure require functional oxime group (R-CH = NOH) which is able to bind the organophosphate agent from enzyme and restore its function. In this thesis, we focused on preparation, identifying structure and specifying physical and chemical properties of new...
Use of lactones in acylceramide synthesis
Moravčík, Štefan ; Opálka, Lukáš (advisor) ; Roh, Jaroslav (referee)
6 Abstract Acylceramides, subgroup of ceramides with ultralong chains, are essential component of extracellular lipid matrix in the uppermost skin layer, stratum corneum. They have crucial role in mammalian survival on dry land. Deeper understanding of their function in physiology of pathophysiology of the skin and their therapeutic potential are hampered by their limited availability. Analysis of the skin surface lipids of the ass (E. asinus) has shown, that these lipids contain up to 56% of unbranched ω-lactones (equolides), from which 51.2% is mono- unsaturated dotriacontanolide and 41.3% is mono-unsaturated triacontanolide. Carbon chain length of these lactones match the most common length of carbon chain in acylceramides (30 and 32 carbon atoms) therefore they could be used in their total synthesis. Aim of this thesis was to isolate mono-unsaturated ω-lactone with 32 carbon chain (dotriacontanolide) from the mixture of donkey skin surface lipids, followed by hydrogenation and transformation to the suitable precursor (succinmidyl ester) in order to find the easiest synthetic path in its conversion to acylceramides. We have tried many synthetic pathways. From direct aminolysis of lactone, through reaction with N-hydroxysuccinimide in various reaction conditions to opening of the lactone to the potassium...
Synthesis and study of 1-O-acylceramides
Jon, Vojtěch ; Vávrová, Kateřina (advisor) ; Opálka, Lukáš (referee)
The extracellular matrix of the uppermost layer of the skin, the stratum corneum (SC), consists of ceramides (Cer), cholesterol (Chol), free fatty acids (FFA) and cholesteryl sulfate (CholS). Cer play an important role in the correct barrier function of mammalian epidermis. A new type of sphingolipids, i.e., 1-O-acyl-Cer, have been found in human SC very recently; however, their role in the SC is unknown. These Cer species contain sphingosine (S) that is N- acylated with non-hydroxylated or α- hydroxylated fatty acid, and moreover, hydroxyl group at C1 in sphingosine is esterified by an additional fatty acid (lignoceric acid, C24 or palmitic acid, C16). Because 1-O-acyl-Cer are not commercially available, we aimed to synthesize physiological 1-O-acyl Cer, i.e., Cer-24NS16, Cer-16NS16 and Cer-24AS16. Moreover, we aimed to study their behaviour on permeability and microstructure of model skin lipid membranes. The 1-O-acyl-Cer were synthesized by an acylation of Cer-NS16 or Cer-AS16 with palmitic or lignoceric acid using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and 4- dimethylaminopyridine. Cer-AS16 was prepared by α-bromination of palmitic acid, substitution of bromine by hydroxyl and N-acylation of sphingosine by the prepared acid in the presence N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide...

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