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Study of porphyrins substituted wich glycosylated steroids
Zelenka, Karel ; Trnka, Tomáš (advisor) ; Jindřich, Jindřich (referee) ; Kefurt, Karel (referee) ; Pouzar, Vladimir (referee)
I I 4. Conclusions This work is focused on syntheses of new zeso-substituted porphyrins containing glycosylated-steroid moieties and study oftheir physico-chemical and supramolecular propertres. In the first part oť this work, procedure for the synthesis of B glycosides 4 or 5 is described. No ťormation of ortohoesters was observed. Next part of this work consists oť searching for suitable protecting group for a saccharide part oť molecule and preparation of steroidaldehydes.Protectedglycosides10, ll,tó, 17,|9a+l9band20wereprepared.Suitable method for preparation ofaldehydes 14, 15, 23,24,29,30 an.34 is described (chapter 3.1). Following part of work describes preparation of porphyrins with protected sugar moiety. Symmetrical Al type porphyrins 35-41 were prepared. Also preparatio n of trans-A2ts1 ýpe porphyrins 43, 44 and A]B type 45, 4ó is described. Preparation oť porphyrins 47.50 with deprotected hydroxyl groups is described (Chapter 3.2). Solvent driven aggregation behavior oť the porphyrins was studied in aqueous solvent mixtures' Formation of aggregates of porphyrin 45 was proved using uv-vis spectroscopy (Chapter 3.3). Considering use oť prepared porphyrins in electrochemistry as a possible electrochemical sensors, polarographic and voltametric studies oť porphyrins 47-19 were per|ormed and showed...
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Carbocyclic analogues of nucleosides and nonnucleoside inhibitors of thymidine phosphorylase
Nencka, Radim ; Hřebabecký, Hubert (advisor) ; Černý, Miloslav (referee) ; Ledvina, Miroslav (referee) ; Kefurt, Karel (referee)
!ntroduction Analogues ofnucleic acid components belong to the most successful classes oftherapeutics. Extensive modifications ofnucreobases, nucreosides and nucleotides led to the discovery ofa huge group of compounds with remarkable biological activity. The most important are perhaps the effects on various severe diseases such as cancer, leukemia or viral infectrons. The essential aim ofthis Thesis was the preparation ofbiologically active compounds related to the nucleic acid components. Since the carbocyclic anďogues ofnucleosides have been a long-time interest of our group, the first part of this work was devoted to the development of practical synthetic routes towards their new derivatives and to the synthesis of the novel analogues for further biological activity screening. However, the preliminary biological tests of the prepared compounds uncovered very promising lead to the compretely different field than it was expected. During the primer studies, I synthesized several 5,6-disubstituted uracils, initially prepared just as moder compounds for development of nover synthetic approaches towards carbocyclic nucleosides, that showed to posses outstanding inhibitory activity against thymidine phosphorylase. Therefore, the development of novel derivatives based on these findings was estabrished as a new...
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Study of porphyrins substituted wich glycosylated steroids
Zelenka, Karel ; Trnka, Tomáš (advisor) ; Jindřich, Jindřich (referee) ; Kefurt, Karel (referee) ; Pouzar, Vladimir (referee)
I I 4. Conclusions This work is focused on syntheses of new zeso-substituted porphyrins containing glycosylated-steroid moieties and study oftheir physico-chemical and supramolecular propertres. In the first part oť this work, procedure for the synthesis of B glycosides 4 or 5 is described. No ťormation of ortohoesters was observed. Next part of this work consists oť searching for suitable protecting group for a saccharide part oť molecule and preparation of steroidaldehydes.Protectedglycosides10, ll,tó, 17,|9a+l9band20wereprepared.Suitable method for preparation ofaldehydes 14, 15, 23,24,29,30 an.34 is described (chapter 3.1). Following part of work describes preparation of porphyrins with protected sugar moiety. Symmetrical Al type porphyrins 35-41 were prepared. Also preparatio n of trans-A2ts1 ýpe porphyrins 43, 44 and A]B type 45, 4ó is described. Preparation oť porphyrins 47.50 with deprotected hydroxyl groups is described (Chapter 3.2). Solvent driven aggregation behavior oť the porphyrins was studied in aqueous solvent mixtures' Formation of aggregates of porphyrin 45 was proved using uv-vis spectroscopy (Chapter 3.3). Considering use oť prepared porphyrins in electrochemistry as a possible electrochemical sensors, polarographic and voltametric studies oť porphyrins 47-19 were per|ormed and showed...
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Acyclic nucleoside phosphonates with expanded purine bases
Čapková, Kateřina ; Holý, Antonín (advisor) ; Černý, Miloslav (referee) ; Kefurt, Karel (referee) ; Hocek, Michal (referee)
Univerzita Karlova Příro dovědecká fakulta Katedra organické a jaderné chemie Akademie věd Ceské Republiky Ústav organické chemie a biochemie S tirrltrffi[n Acyklické nukleo sidfo sfon áty rozšířenoupurinovou bazí Kateřina Čapková Shrnutí disertačnípráce Praha 2006 -tt ai-''- ffi-'.--.-/ /{ía' s Acyklické nukleosid fosfonáty předstalují velice zajimavou skupinu nukleotidových analogů s protivirovými, cýostatickj.rni a antiprotozoá|ními účinky.Jsou aktivní nejen proti širokému spektru DNA viru (herpesviry, poxviry, adenoviry, papillomaviry), ale i proti retrovirům (virus hepatitidy B, HIV). Nejvýznamnějšími představiteli celé skupiny jsou PMEA (adefovir, v klinické praxi ve formě adefovir dipivoxil), schválený pro léčbuhepatitidy B (HepseraTM), dále (fi).PMPA (teno-Qvir. v klinické praxi jako tenofovir disoproxil fumarát), schválený pro léčbuAIDS (Viread.'u') a (S)-HPMPC (cidofovir),-schválený pro léčbucýomegalovirové retinitidy u imunosuprimovaných pacientů (VistideTM). 1 V rámci hledání nových potenciálních virostatik a cýostatik bylo mým úkolem připravit série několika nových typůmodifikovaných acyklických nukleosid fosfonátů, konkrétně s tricyklickou bazi odvozenou od původnípurinové baze. Tricyk|ické baze23 ;so., zajímavé předevšímkvůli své fluorescencí,která umoŽňuje snadnou detekci a sledování osudu...
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Synthesis of oligosaccharides of Dhexosamine type-potential ligands of activating receptors of NK cells
Kovalová, Anna ; Ledvina, Miroslav (advisor) ; Černý, Miloslav (referee) ; Kefurt, Karel (referee) ; Holý, Antonín (referee)
stu(trd oÍgaŮáůr' ďthercce#*' lsťÍees€pd-e fuandffig sibs.. CoNcLusroN In the course of this work, we prepared oligosaccharides containing 2-acetamido-2- deoxyglucopyranose and 2-acetamido-2-deoxygalactopyranose units and tested them for binding to NK cell receptors NKR-p1 and CD69. Branched oligosaccharides are first effective mimetics of natural ligands of CD69. We successfully completed the synthesis despite some challenging problems (multiple glycosylations, H-bonds), and we also obtained results, which contribute to the understanding of a relevant biological question. APLICABILITY AND PERSPECTIVES Although the synthesized o|igosaccharides were speciÍica||y designed as |igands for lectin receptors of NK cells, they may have other uses too. We intend to introduce linkers to the reducing position of the oligosaccharides to enable their presentation on dendrimeric structures. These multiple glycodendrimers can substitute natural multiantenar ligands. Moreover, oligosaccharides of this type might be used as a part of vector systems of new generation targeted combined chemo- and immunotheraoeutics. This Work was suppofted by grants No. 241/2013/B-CH/PřF and 416/2004/B-CH/PřF of GAUK' No. QF31 1 5/2003 of Ministry of Agricutture of cR, 203/00/0071 of Grant Agency of cR, by research project No 24 055 05O6.and...
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Carbocyclic analogues of nucleosides and nonnucleoside inhibitors of thymidine phosphorylase
Nencka, Radim ; Hřebabecký, Hubert (advisor) ; Černý, Miloslav (referee) ; Ledvina, Miroslav (referee) ; Kefurt, Karel (referee)
!ntroduction Analogues ofnucleic acid components belong to the most successful classes oftherapeutics. Extensive modifications ofnucreobases, nucreosides and nucleotides led to the discovery ofa huge group of compounds with remarkable biological activity. The most important are perhaps the effects on various severe diseases such as cancer, leukemia or viral infectrons. The essential aim ofthis Thesis was the preparation ofbiologically active compounds related to the nucleic acid components. Since the carbocyclic anďogues ofnucleosides have been a long-time interest of our group, the first part of this work was devoted to the development of practical synthetic routes towards their new derivatives and to the synthesis of the novel analogues for further biological activity screening. However, the preliminary biological tests of the prepared compounds uncovered very promising lead to the compretely different field than it was expected. During the primer studies, I synthesized several 5,6-disubstituted uracils, initially prepared just as moder compounds for development of nover synthetic approaches towards carbocyclic nucleosides, that showed to posses outstanding inhibitory activity against thymidine phosphorylase. Therefore, the development of novel derivatives based on these findings was estabrished as a new...
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