Dizajn i priprava imidazolnih, pirazolnih i 5-metilisatinskih reaktivatora acetilkolinesteraze

master's thesis

• Title (english): Design and preparation of imidazole, pyrazole and 5-methylisatin acetylcholinesterase reactivators
• Author: Toni Divjak
• Mentor: Dijana Pešić (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Morana Dulić (član povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-02-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom diplomskom radu sintetizirana su tri prekursora Ugijeve reakcije koji sadrže oksimsku
i karboksilnu skupinu: 6-(2-hidroksiiminometilimidazol-1-il)heksanska kiselina, 2-(4-
hidroksiiminometil-pirazol-1-il)heksanska kiselina i 7-(5-metil-3-(hidroksiimino)-2-
oksoindolin-1-il)heksanska kiselina. Dobiveni 5-metilisatinski prekursor poslužio je kao
reaktant za Ugijevu reakciju s benzil-aminom, tert-butil-izocijanidom i formaldehidom pri
čemu se usporedila mogućnost izvođenja sinteze u otopini, mikrovalnom reaktoru te
mehanokemijski. Pripravljeni spojevi pročišćeni su dostupnim kromatografskim tehnikama i
karakterizirani dostupnim analitičkim metodama (UPLC-UV/MS, 1D, 2D NMR). U
računalnom dijelu rada uspoređeno je vezanje produkta Ugijeve reakcije i literaturno opisanih
reaktivatora u aktivnom mjestu sarinom inhibiranoga enzima acetilkolinesteraze pomoću
molekulskog uklapanja.

Abstract (english)

In this diploma thesis new Ugi reaction's precursors containing oxime and carboxyl groups were
synthesized: 6-(2-hydroxyiminomethylimidazol-1-yl)hexanoic acid, 2-(4-
hydroxyiminomethyl-pyrazol-1-yl)hexanoic acid and 7-(5-methyl-3-(hydroxyimino)-2-
oxoindolin-1-yl)hexanoic acid. The 5-methylisatin precursor was used as a reactant for the Ugi
reaction with benzyl-amine, tert-butyl-isocyanide and formaldehyde. Besides the classical
syntheses in solution, the Ugi reaction was performed in a microwave reactor as well as
mechanochemically. The compounds were purified by available chromatographic techniques
and characterized by available analytical methods (UPLC-UV/MS, 1D, 2D NMR). The binding
of the Ugi reaction's products and acetylcholinesterase reactivators in the active site of the sarininhibited enzyme acetylcholinesterase were compared by molecular docking.

• Keywords: mehanokemijska sinteza; mikrovalna sinteza; oksimi; Ugijeva reakcija
• Keywords (english): oximes; mechanochemistry; microwave synthesis; Ugi reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:217:683772
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-02-17
• Created on: 2023-03-29 11:02:11