Priprava i karakterizacija bioaktivnih spojeva temeljenih na 1-azabiciklo[2.2.2]oktanu

doctoral thesis

• Title (english): Synthesis and characterization of bioactive compounds based on 1-azabicyclo[2.2.2]octane
• Author: Andreja Radman Kastelic
• Mentor: Ines Primožič (mentor)
• Committee member: Iva Juranović Cindrić (predsjednik povjerenstva)
• Committee member: Maja Majerić-Elenkov (član povjerenstva)
• Committee member: Anita Bosak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2019-11-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

U okviru ove disertacije opisana je priprava 3-hidroksiimino-, 3-dodecilamino, 3-
(N,N-dimetilkarbamoiloksi)-, 3-(N,N-dietilkarbamoiloksi), 3-(N-fenilkarbamoiloksi)-, te 3-
(N,N-difenilkarbamoiloksi)kinuklidina, kao i 2-(kinuklidin-3-iliden)kinuklidin-3-ona i
njegovog ketoksima. Spojevi su sintetizirani klasičnim postupcima organske sinteze, a
ketoksim kinuklidina i mehanokemijskom sintezom. Ispitan je potencijal mehanokemijske
sinteze oksima na nizu aldehida i ketona koji u svojoj strukturi imaju dušikove atome različite
bazičnosti te je pokazano da su reakcije moguće uz katalitičku količinu otapala i bez dodatka
baze. Nadalje, kvaternizacijom spojeva s metil-jodidom, but-3-en-1-il-bromidom i različito
para i meta supstituiranim benzil-bromidima pripravljena su 42 derivata, od kojih 37 do sada
nisu opisani u literaturi. Svi pripravljeni spojevi dobiveni su u zadovoljavajućem iskorištenju
te im je struktura dokazana standardnim analitičkim metodama, a primjenjena je i
spektroskopija nuklearne magnetske rezonancije za određivanje optičke čistoće kiralnih
amina. Svi spojevi su pokazali bioaktivnost: oksimi i amini antibiotski potencijal, a karbamati
inhibicijski potencijal prema kolinesterazama. Molekulskim modeliranjem određen je način
vezanja N,N-dimetilkarbamata u aktivnom mjestu AChE.

Abstract (english)

In this thesis, the syntheses of 3-hydroxiimino-, 3-dodecylamino-, 3-(N,Ndimethylcarbamoyl)
oxy-, 3-(N,N-diethylcarbamoyl)oxy-, 3-(N-phenylcarbamoyl)oxy-, 3-
(N,N-diphenylcarbamoyl)oxyquinuclidine, as well as the condesation product of
quinuclidine-3-on and its ketoxime are described. The possibility of mechanochemical
synthesis (without the addition of external base and with catalytic amount of solvent) of
oximes from carbonyl compounds that have nitrogen atoms of various bacisity was also
determened. Furthermore, prepared compounds were quaternized with methyl iodide, but-3-
en-1-yl bromide, and differently substituted meta and para benzyl bromides. 42 compounds
were prepared in that manner, from which 37 for the first time. All compounds were prepared
in good yields and were characterized by standard analytical methods. Bioactivity of
compounds was tested. Oximes and amine derivatives showed antibacterial potential. The
interaction of carbamates with cholinesterases was determined experimentaly and the mode
of binding of 3-(N,N-dimethylcarbamates within the active site was determined.

• Keywords: kinuklidin; amini; oksimi; karbamati; autokondenzacija; mehanokemija; bioaktivni spojevi
• Keywords (english): quinuclidine; amine; oxime; carbamates; autocondensation; mechanochemistry; bioactive compounds
• Language: croatian
• URN:NBN: urn:nbn:hr:217:662978
• 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: 123 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-11-29
• Created on: 2020-01-29 12:03:27