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Modification of the aglycone Josamycin using a regioselective nucleophilic substitution type SN1' and Huisgen dipolar cycloaddition
Joanna Domagalska
Abstract
The aim of the dissertation was modifications of the aglycone’s structure of 16-membered macrolide antibiotic – josamycin. 31 new type derivatives of josamycin containing introduced new triazole arm were obtained by a combination of a substitution reaction in the allyl system and the 1,3-dipolar Huisgen cycloaddition. Structures and stereochemistry of new leucomycin analogs containing new triazole functionalized arm at C(13) were determined by FT-IR, 1D and 2D NMR and molecular optimization B88 LYP (GGA) DFT method. Unexpected mechanism of substitution SN1’ within diene system was established by reaction rate analysis at different conditions. Biological tests in combination with the molecular modeling MOG PM6 indicated that the structure of new triazole arm at C(13) of the aglycone contributes leucomycins’ activity, both antimicrobial and anticancer. The most active compounds containing triazole arm substituted by saccharides also have high selectivity in cancer cells, which is important in the context of potential future applications. Additionally, demonstrated that the lack of the aldehyde in the structure of the macrolide lactone type leucomycin is not necessary to achieve a high cytotoxic and antibacterial properties by this class of novel antibiotics.- Record ID
- UAMbe4cb700b08944ba85b8fb54e335bd4d
- Diploma type
- Doctor of Philosophy
- Author
- Title in Polish
- Modyfikacja aglikonu josamycyny z wykorzystaniem regioselektywnej substancji nukleofilowej typu SN1' i dipolarnej cykloaddycji Huisgena
- Title in English
- Modification of the aglycone Josamycin using a regioselective nucleophilic substitution type SN1' and Huisgen dipolar cycloaddition
- Language
- pol (pl) Polish
- Certifying Unit
- Wydział Chemii [nowa struktura organizacyjna] (SNŚ/WC)
- Scientific discipline (2.0)
- Status
- Finished
- Year of creation
- 2016
- Defense Date
- 16-06-2016
- Title date
- 16-06-2016
- Supervisor
- URL
- http://hdl.handle.net/10593/14719 Opening in a new tab
- Keywords in English
- antibiotics, antibacterial activity, josamycin, spectroscopy
- Abstract in English
- The aim of the dissertation was modifications of the aglycone’s structure of 16-membered macrolide antibiotic – josamycin. 31 new type derivatives of josamycin containing introduced new triazole arm were obtained by a combination of a substitution reaction in the allyl system and the 1,3-dipolar Huisgen cycloaddition. Structures and stereochemistry of new leucomycin analogs containing new triazole functionalized arm at C(13) were determined by FT-IR, 1D and 2D NMR and molecular optimization B88 LYP (GGA) DFT method. Unexpected mechanism of substitution SN1’ within diene system was established by reaction rate analysis at different conditions. Biological tests in combination with the molecular modeling MOG PM6 indicated that the structure of new triazole arm at C(13) of the aglycone contributes leucomycins’ activity, both antimicrobial and anticancer. The most active compounds containing triazole arm substituted by saccharides also have high selectivity in cancer cells, which is important in the context of potential future applications. Additionally, demonstrated that the lack of the aldehyde in the structure of the macrolide lactone type leucomycin is not necessary to achieve a high cytotoxic and antibacterial properties by this class of novel antibiotics.
- Thesis file
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- File: 1
- PRACA DOKTORSKA.pdf
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- Uniform Resource Identifier
- https://researchportal.amu.edu.pl/info/phd/UAMbe4cb700b08944ba85b8fb54e335bd4d/
- URN
urn:amu-prod:UAMbe4cb700b08944ba85b8fb54e335bd4d