Totalna sinteza marinoaziridina A i B te njihovih derivata

doctoral thesis

• Title (english): Total synthesis of marinoaziridines A, B, and their derivatives
• Author: Anđela Buljan
• Mentor: Marin Roje (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Nives Galić (član povjerenstva)
• Committee member: Senka Djaković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-12-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

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.

Abstract (english)

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.

• Keywords: aziridini; enantiomeri; enantioselektivnost; dijastereoselektivnost marinoaziridini; marinoepoksidi; sumporovi ilidi; totalna sinteza
• Keywords (english): aziridines; enantiomers; enantioselectivity; diastereoselectivity; marinoaziridines; marinoepoxides; sulfur ylides; total synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:716821
• Promotion: 2023
• Project: Number: DOK-2018-01-9531; Title: Bioprospecting Jadranskog mora; Title: DOK - Young Researchers’ Career Development Project - Training New Doctoral Students; Leader: Bono Lučić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: DOK
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: LXXVI, 256 str. ; 30 cm
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-12-20
• Created on: 2023-02-02 11:38:40