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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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Synthesis of deuterium labelled neuroactive steroids.
Slavíčková, Alena ; Chodounská, Hana (advisor) ; Pouzar, Vladimir (referee)
The work si focused on the synthesis of deuterium-labelled neuroactive steroids useful as inner standards for determination of their farmaco-kinetics and bioavailibility. The starting material for the syntheses was comercial 11α-hydroxyprogesterone 16. The target compound, 20-Oxo-[9,12,12-2 H3]5β-pregnan-3α-yl L-glutamyl 1-ester (47), contains 3 deuterium atoms in positions 9α, 12α, 12β. Alternative target with a 18-functionalized group (34) was also studied. It will be used for an analogue with deuterium atoms on carbon C-18.
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Preparation of Lupane and 18alfa-Oleanane Triterpenoids for Biological Testing
Kvasnica, Miroslav ; Šarek, Jan (advisor) ; Klinotová, Eva (referee) ; Drašar, Pavel (referee) ; Pouzar, Vladimir (referee)
T =t a a !r a a a t I a a a - - 5. CONCLUSION 5. CONCLUSION This work was focused on the synthesis of new triterpenoids - named highly oxidized derivatives of 18o-oleanane, their reductive products or products with heteroatoms, for example fluorine, nitrogen, suflur or phosphorus. Part of this thesis was focused on reactions of lupane and I 8cr-oleanane triterpenoids with Lawesson's reagent. l. Highly oxidized l8cr-oleanane derivatives were synthesised, in particular on A-ring. Commercially available reagents were used for these oxidations: MCPBA, SeOr or pero- xyacetic acid (as a persteril). A group of seco derivatives was prepared by reactions with in situ prepared RuOo. A great deal of this section has been already published in scienti- fic journal.2a 2. Agroup of 18ct-oleanane alcohols (e.g. L5,16a,16b, 19, 20,22) was prepared from some oxidized derivatives (e.g.2,3, 13, L8) by reactions with LiAlHo or NaBI{.. 3. Reactions of some ketones were carried out (e.g. 3) with fluorinating agent DAST for preparation of new fluorous derivatives (e.g. 24,25). The same ketones reacted with ethanedithiol to afford new dithiolanes (e.g. 26). Diketone 3 was'also used for synhesis of several nitrogen containing derivatives. Preparation of pyrazine 27 and quinoxaline 28 has been already published in scientific...
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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 Lupane and 18alfa-Oleanane Triterpenoids for Biological Testing
Kvasnica, Miroslav ; Šarek, Jan (advisor) ; Klinotová, Eva (referee) ; Drašar, Pavel (referee) ; Pouzar, Vladimir (referee)
T =t a a !r a a a t I a a a - - 5. CONCLUSION 5. CONCLUSION This work was focused on the synthesis of new triterpenoids - named highly oxidized derivatives of 18o-oleanane, their reductive products or products with heteroatoms, for example fluorine, nitrogen, suflur or phosphorus. Part of this thesis was focused on reactions of lupane and I 8cr-oleanane triterpenoids with Lawesson's reagent. l. Highly oxidized l8cr-oleanane derivatives were synthesised, in particular on A-ring. Commercially available reagents were used for these oxidations: MCPBA, SeOr or pero- xyacetic acid (as a persteril). A group of seco derivatives was prepared by reactions with in situ prepared RuOo. A great deal of this section has been already published in scienti- fic journal.2a 2. Agroup of 18ct-oleanane alcohols (e.g. L5,16a,16b, 19, 20,22) was prepared from some oxidized derivatives (e.g.2,3, 13, L8) by reactions with LiAlHo or NaBI{.. 3. Reactions of some ketones were carried out (e.g. 3) with fluorinating agent DAST for preparation of new fluorous derivatives (e.g. 24,25). The same ketones reacted with ethanedithiol to afford new dithiolanes (e.g. 26). Diketone 3 was'also used for synhesis of several nitrogen containing derivatives. Preparation of pyrazine 27 and quinoxaline 28 has been already published in scientific...
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Preparation of neuroactive steroids for study of NMDA receptors
Vidrna, Lukáš ; Hodek, Petr (advisor) ; Pouzar, Vladimir (referee)
Neurosteroids are an important group of substances that affect communication between neurons. They act as allosteric modulators of membrane receptors for neurotransmitters. One of the most important systems influenced by neurosteroids are NMDA receptors; however, a binding site(s) for their inhibition by steroids have not been found yet. This work is focused on the synthesis of fluorescently labeled photoaffinity probe, which may help explain the structure and location of binding site(s) and simplify the development of new neuroprotectives. A structural analogue of the endogenous neurosteroid, (20S)-20-Azido-5β-pregnan- 3α-yl N-(7-nitrobenz-2-oxa-1,3-diazole-4-yl)-L-glutamyl 1-ester (8), was prepared. The structure of compound 8 includes photolabile azido group, as well as covalently bounded fluorescent NBD group. In addition, a photoaffinity probe with a modified steroid skeleton - pyridinium 17aα-azido-17α-methyl-17a-homo-5β-androstan-3α-yl 3-sulfate (29) - was synthesized. The ability of compound 8 and 29 to inhibit activated NMDA receptor has been verified for recombinant NR1-1a/NR2B receptors expressed in HEK293 cells using a patch-clamp technique. Additionally, the IC50 values of compounds 8 and 29 have been calculated. (In Czech) Key words: neuroactive steroid, NMDA receptor, photoffinity...
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Synthesis of deuterium labelled neuroactive steroids.
Slavíčková, Alena ; Pouzar, Vladimir (referee) ; Chodounská, Hana (advisor)
The work si focused on the synthesis of deuterium-labelled neuroactive steroids useful as inner standards for determination of their farmaco-kinetics and bioavailibility. The starting material for the syntheses was comercial 11α-hydroxyprogesterone 16. The target compound, 20-Oxo-[9,12,12-2 H3]5β-pregnan-3α-yl L-glutamyl 1-ester (47), contains 3 deuterium atoms in positions 9α, 12α, 12β. Alternative target with a 18-functionalized group (34) was also studied. It will be used for an analogue with deuterium atoms on carbon C-18.
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