| Abstract [eng] |
Master thesis of Gintarė Sapežinskaitė “Synthesis of 5-Substituted-7H-imidazo[2,1-b][1,3]thiazines for Inhibition of Amyloid Aggregation” Supervisor doc. dr. Ieva Žutautė. Vilnius University Faculty of Medicine Institute of Biomedical Sciences Pharmacy and Pharmacology Center. Vilnius, 2024. Aim of study – to synthesize 5-substituted-7H-imidazo[2,1-b][1,3]thiazines for the search for inhibitors of amyloid protein aggregation. Study objectives: 1. To choose which 5-substituted-7H-imidazo[2,1-b][1,3]thiazines to synthesize, i.e. choose substituents. Perform retrosynthetic analysis of target compounds and apply synthetical methods. 2. To synthesize the target compounds from the designed alkynylimidazoles via gold chloride catalyzed intramolecular nucleophilic cyclization. 3. To identify and substantiate the structures of target compounds using spectroscopic analysis methods. Study methods. The object of the master's thesis is the synthesis of new compounds that could be characterized by inhibition of protein amyloid aggregation. Synthesis was carried out using various methodologies, reactions were evaluated using thin-layer chromatography (TLC) method. Structures of new compounds were elucidated by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, IR spectroscopy, melting points. Results and conclusions. Based on compounds of various structures already tested in the laboratory, seven substituents were selected according to the most favorable data: 2-methylphenyl, 4-methoxyphenyl, 3-methoxyphenyl and four different 3-phenoxyacetamides. Retrosynthetic analysis of 5-substituted-7H-imidazo[2,1-b][1,3]thiazines was performed, appropriate methodologies were applied and target compounds were synthesized in 4 main stages. All nine target compounds (5a-f, 6a-d) were new and not yet described in the literature. The structure of known intermediate compounds was confirmed with melting point and 1H NMR. The structure of new, not yet described compounds has been fully identified and proven using melting point, 1H and 13C NMR spectra, IR spectra and HRMS analysis. |
