Total synthesis of marinoaziridines A, B, and their derivatives
| Autor: | Buljan, Anđela |
|---|---|
| Přispěvatelé: | Roje, Marin |
| Jazyk: | chorvatština |
| Rok vydání: | 2022 |
| Předmět: |
aziridini
sulfur ylides marinoepoxides marinoaziridines sumporovi ilidi enantioselektivnost dijastereoselektivnost marinoaziridini marinoepoksidi enantiomers PRIRODNE ZNANOSTI. Kemija diastereoselectivity NATURAL SCIENCES. Chemistry totalna sinteza aziridines enantioselectivity enantiomeri udc:54(043.3) Kemija. Kristalografija. Mineralogija total synthesis Chemistry. Crystallography. Mineralogy |
| Popis: | U okviru ove doktorske disertacije razvijena je prva totalna sinteza marinoaziridina B, metiliranog derivata marinoaziridina A te njihovih strukturnih derivata. Kvantno-kemijskim izračunima primjenom DFT funkcionala B3LYP uz korištenje baznog skupa 6-311++G(d,p) optimizirane su strukture marinoaziridina A i B, te je ispitan solvatacijski utjecaj (kloroform) na ravnotežu para tautomera kinolin-2(1H)-ona u strukturi marinoaziridina A i B. Razvijena je enantioselektivna metoda za razdvajanje enantiomera marinoepoksida i marinoaziridina na polisaharidnim kiralnim nepokretnim fazama utemeljenim na derivatima amiloze i celuloze primjenom visokodjelotvorne tekućinske kromatografije i superkritične fluidne kromatografije. Apsolutna konfiguracija uspješno je određena primjenom računskih i kirooptičkih metoda (elektronski cirkularni dikroizam, ECD i vibracijski cirkularni dikroizam, VCD). Biološka ispitivanja marinoaziridina i odabranih derivata provedena su na tri stanične linije (MCF-7 rak dojke, H-460 rak pluća i HEK293T embrionalnog bubrega) te na bakterijskim kulturama Escherichia Coli i Staphylococcus aureus. Toksikološka ispitivanja načinjena su primjenom testa na embrijima zebra ribica. Within this dissertation, the total synthesis of marinoaziridine B, the methylated derivative of marinoaziridine A and their structural derivatives was developed for the first time. The structures of marinoaziridines A and B were optimized by quantum-chemical calculations using the DFT functional B3LYP with the use of the 6-311++G(d,p) basis set, and the solvation effect (chloroform) on the equilibrium of the tautomeric pairs of quinolin-2(1H)-on was examined. An enantioselective method was developed for the separation of enantiomers of marinoepoxide and marinoaziridine on polysaccharide chiral stationary phases based on amylose and cellulose derivatives using high performance liquid chromatography and supercritical fluid chromatography. The absolute configuration was successfully determined using computational and chiroptical methods (electronic circular dichroism, ECD and vibrational circular dichroism, VCD). Biological tests of marinoaziridine and selected derivatives were performed on three cell lines (MCF-7 breast cancer, H-460 lung cancer and HEK293T embryonic kidney) and on bacterial cultures of Escherichia Coli and Staphylococcus aureus. Toxicological tests were performed using a test on zebrafish embryos. |
| Databáze: | OpenAIRE |
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