Sinteza i modeliranje novih oksimskih derivata furostilbena kao reaktivatora kolinesteraza

master's thesis

• Title (english): Synthesis and modeling of new oxime derivatives of furostilbene as cholinesterase reactivators
• Author: Ana Vukovinski
• Mentor: Irena Škorić (mentor)
• Committee member: Irena Škorić (predsjednik povjerenstva)
• Committee member: Dragana Vuk (član povjerenstva)
• Committee member: Danijela Barić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-07-09, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Novi oksimski derivati furostilbena 10-14 sintetizirani su u svrhu proučavanja biološke aktivnosti s naglaskom na reaktivaciju acetilkolinesteraze (AChE) i butirilkolinesteraze (BChE). Prvi korak sinteze je Wittigova reakcija, čime nastaju cis- i trans-izomeri furostilbena 1-4. U drugom koraku furostilbeni su podvrgnuti Vilsmeier-Haackovom formiliranju, u svrhu dobivanja aldehida 5-9, koji se u trećem stupnju reakcije prevode u oksime 10-14, koji literaturno nisu poznati. U svakoj provedenoj reakciji sinteze oksima teorijski mogu nastati četiri izomera, s obzirom na konfiguraciju dvostruke veze između dva atoma ugljika (cis- i trans-) te s obzirom na konfiguraciju dvostruke veze između ugljika i dušika oksimske skupine (syni anti-). Oksim 13 jedini daje sva četiri izomera u dovoljnim količinama za izolaciju, dok sukod spojeva 10, 11, 12 i 14 neki izomeri nastali samo u tragovima, dok su drugi prevladavali. Sintetizirani i izolirani novi spojevi okarakterizirani su 1D i 2D NMR tehnikama. Računalnim modeliranjem istraživana je elektronska struktura dobivenih oksimskih derivata i njihova termodinamička stabilnost, te su računalno ispitivani kao potencijalni reaktivatori inhibirane AChE i BChE.

Abstract (english)

New oxime derivatives of furostilbenes 10-14 were synthesized for the purpose of studying biological activity with the emphasis on reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The first step of the synthesis is the Wittig reaction leading to the cis- and trans-isomers of furostilbenes 1-4. In the second step, furostilbenes are subjected to the Wilsmeier-Haack formulation, yielding aldehydes 5-9, which are in the third reaction phase converted to oximes 10-14, compounds unknown in the literature. In each oxime synthesis carried out, four isomers can theoretically be formed, given the configuration of the double bond between the two carbon atoms (cis- and trans -), and the configuration of the double bond between the carbon and nitrogen of the oxime group (syn- and anti-). Only oxime 13 gives all four isomers, while all isomers of compounds 10, 11, 12 and 14 are not obtained in enough quantity for characterization and only some isomers were predominant. The synthesized and isolated new compounds were characterized using 1D and 2D NMR techniques. The electronic structure of the obtained oxime derivatives and their thermodynamic stability were investigated by computer modeling and they were computer tested as potential reactivators of inhibited AChE and BChE.

• Keywords: furostilbeni; oksimi; kolinesteraze; reaktivacija AChE i BChE; računalno modeliranje
• Keywords (english): furostilbene; oximes; cholinesterases; AChE and BChE reactivation; computer modeling
• Language: croatian
• URN:NBN: urn:nbn:hr:149:916647
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-04-06 14:16:21