Novi pristup sintezi bioaktivnih spojeva kinuklidina i imidazola

doctoral thesis

• Title (english): A new approach for the synthesis of bioactive quinuclidine and imidazole compounds
• Author: Zlatan Spahić
• Mentor: Ines Primožič (mentor)
• Committee member: Nikola Cindro (predsjednik povjerenstva)
• Committee member: Maja Majerić-Elenkov (član povjerenstva)
• Committee member: Iva Juranović Cindrić (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 ovog rada pripravljena je knjižnica od 63 derivata potencijalno bioaktivnih oksima,
etera i karbamata oksima, te α-acilamino-amida koji sadrže imidazolijevu ili kinuklidinijevu
jezgru. Dodatno, sintetizirani su i α-acilamino-amidi koji sadrže i druge heterocikličke
podjedinice (piridin, indol, tetrazol i tiofen) kako bi se dobila što raznovrsnija knjižnica novih
spojeva koji do sada nisu opisani u literaturi. U sintezi spojeva primijenjene su klasične metode
sinteze, mehanokemijske i sinteze potpomognutim mikrovalnim zračenjem. Varirani su uvjeti
te uspoređene brzine i iskorištenja reakcija, ali i stereokemija nastalih produkata kod etera
oksima. Optimirani su uvjeti za stereospecifičnu sintezu četiri etera oksima kinuklidina
mehanokemijskom sintezom bez otapala i uz natrijev hidroksid kao bazu (nastaje anti izomer).
Za određivanje omjera izomera etera oksima te konformera α-acilamino-amida u otopini
primijenjena je spektroskopija nuklearne magnetske rezonancije. Mehanizam i stereokemija
nastanka etera oksima kinuklidin-3-ona te konformacijski prostor α-acilamino-amida studirani
su kvantno-kemijskim proračunima.

Abstract (english)

In this work, a library of 63 derivatives of potentially bioactive oximes, oxime ethers, oximes
carbamates, and α-acylamino-amides containing an imidazolium and/or quinuclidinium
nucleus was prepared. In addition, α-acylamino-amides containing other heterocyclic subunits
(pyridine, indole tetrazole and thiophene) were also synthesized in order to obtain the most
diverse library of new compounds that have not been described in the literature so far. Classical
methods of synthesis in solution, mechanochemical and microwave synthesis were used for the
synthesis of compounds. The conditions were varied and the speed and yields of the reactions
were compared, as well as the stereochemistry of the products formed in the case of ether
oximes. The conditions for the stereospecific synthesis of four quinuclidine oxime ethers were
optimized by mechanochemical synthesis without solvent and with sodium hydroxide as a base
(anti isomer is formed). Nuclear magnetic resonance spectroscopy was used to determine the
ratio of ether oxime isomers and α-acylamino-amide conformers in the solution. The
mechanism and stereochemistry of quinuclidin-3-one oxime ether formation and the
conformational space of α-acylamino-amide were studied by quantum-chemical calculations.

• Keywords: derivati oksima; klasična sinteza; mehanokemija; sinteze potpomognuta mikrovalnim zračenjem; α-acilamino-amidi; Ugijeva reakcija
• Keywords (english): oxime derivatives; classical synthesis; mechanochemistry; microwave synthesis; α-acylamino-amides; Ugi reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:217:299373
• Promotion: 2023
• 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: 109 str. ; 30 cm
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-12-20
• Created on: 2023-01-31 14:35:58