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Selectively substituted cyclodextrins for analytical and pharmaceutical applications
Benkovics, Gábor ; Jindřich, Jindřich (advisor) ; Lhoták, Pavel (referee) ; Šindelář, Vladimír (referee)
3 Selectively substituted cyclodextrins for analytical and pharmaceutical applications Abstract This thesis is focused on the selective modification of cyclodextrins, and its primary aim is the preparation and characterization of mono- and persubstituted derivatives of cyclodextrins in a regioselective and straightforward manner. The work is divided into two main parts describing synthetic strategies and applications of modified cyclodextrins with one or several substituents, respectively. The first section deals with the introduction of a single chromophoric moiety on the cyclodextrin scaffold such as cinnamyl, rhodaminyl, fluoresceinyl and eosinyl groups. The complete set of monocinnamyl-α-cyclodextrin regioisomers has been prepared by direct alkylation, and the self-assembling properties of the corresponding regioisomers were thoroughly investigated by dynamic light scattering and NMR experiments. These investigations revealed that the different isomers (mono-6-O-, mono-2-O- and mono-3-O- cinnamyl-α-cyclodextrin) form distinct supramolecular species through intermolecular association. A fast method for the unambiguous identification of the pure regioisomers has also been developed based on a series of 2D NMR measurements. Xanthene-modified β-cyclodextrins, other representatives of monosubstituted...
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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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Preparation of alfa(1-4)-linked disaccharides containing D-glukosamine units
Škríba, Anton ; Veselý, Jan (advisor) ; Jindřich, Jindřich (referee)
Abstract The aim of this diploma thesis is a preparation of disaccharide composed from two glucosamine units with 1,2-cis-(1→4)-O-glycosidic bond with the attached linker on reducing end, containing an azide functional group. The first part is focused on synthesis of glycosyl acceptor and glycosyl donor, derived from D-glucosamine, suitable for the construction of 1,2-cis-(1→4)-O-glycosidic linkage. The second part of this work describes the optimization of the glycosylation reaction conditions and also subsequent transformation of disaccharide GlcNAc-α-(1→4)-GlcNAc skeleton.
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Preparation of γ-cyclodextrin derivatives usable for construction of self-assembled structures
Bláhová, Markéta ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This thesis is focused on the preparation of monosubstituted derivatives of -cyclodextrin ( -CD) which can form supramolecular polymers. These polymers can be utilized in capillary electrophoresis. Set of monosubstituted 2I -O-, 3I -O- a 6I -O-(3-(naphthalen-2-yl)prop-2-en-1-yl) derivatives of -CD was prepared (naphthylallyl derivatives). Reaction was performed by cross metathesis of O-allyl derivatives of -CD with a 2-vinylnaphthalene in yields 16 - 25 %. Hoveyda-Grubbs 2nd generation catalyst was used. Alkylation of -CD with 2-(3-bromoprop-1-enyl)naphthalene followed by peracetylation of remaining hydroxyl groups and separation of isomers resulted in the per-O-acetyl-3I -O- a per-O- acetyl-6I -O-(3-(naphthalen-2-yl)prop-2-en-1-yl)- -CD in yields 5 and 1 %. A set of dimers of -CD 1,4-bis( -CD-2I -O-yl)-but-2-ene, 1,4-bis( -CD-3I -O-yl)-but-2-ene and 1,4-bis( - CD-6I -O-yl)-but-2-ene was prepared, too. Reaction was performed by cross metathesis of O-allyl derivatives of -CD in yields 1 - 8 % using again Hoveyda-Grubbs 2nd generation catalyst. The dimers of naphthalene guests (1,2-bis(naphthalen-2-yl)ethene and 1,2-bis(naphthalen-2-yl)ethane) for preparation of complexes with CD dimers were also prepared. Further optimization of synthesis of naphthylallyl derivatives of -CD was carried out. These...
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Synthesis of beta-cyclodextrin derivatives for medicinal applications
Popr, Martin ; Jindřich, Jindřich (advisor) ; Veselý, Jan (referee)
Synthesis of monosubstituted β-cyclodextrin derivatives for medicinal applications Abstract This thesis is focused on preparation of a set of β-cyclodextrin derivatives with potential use as scaffolds for a construction of novel MRI contrast agents. Firstly, the skeleton of native β-CD was selectively persubstituted at possitions 6 and equipped with azide functions. Per-6-azido-β-CD was then monosubstituted on secondary face of the macrocycle. (E)-cinnamylbromide and propargylbromide were chosen as suitable reagents. The monosubstitution reaction afforded two types of regioisomers, substituted at position 2I -O- or 3I -O-. These regioisomers were sucessfully separated via preparative column chromatography after peracetylation of all free hydroxyl groups. 2I -O-, 3I -O-formylmethyl- and 3I -O- karboxymethyl- analogues were prepared by oxidative transformation of cinnamyl group. Finally the usability of the formylmethyl- derivative for covalent binding with suitable substrate via reductive amination was confirmed. Keywords: cyclodextrins, monosubstitution, cinnamyl, propargyl, formylmethyl, carboxymethyl, reductive amination, MRI, contrast agents
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