Priprava peptidomimetika Ugijevom višekomponentnom reakcijom

master's thesis

• Title (english): Preparation of peptidomimetics with Ugi multicomponent reaction
• Author: Lucija Hadrović
• Mentor: Ines Primožič (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Jana Pisk (član povjerenstva)
• Committee member: Adriana Kenđel (član povjerenstva)
• Committee member: Nikola Cindro (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2024-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je priprava šest peptidomimetika Ugijevom reakcijom koji do sada nisu opisani u literaturi. Za sintezu odabranih spojeva varirana je karboksilna komponenta te su korištene benzojeva kiselina, 3-brombenzojeva kiselina, 3-klorbenzojeva kiselina, 3-nitrobenzojeva kiselina, octena kiselina i 3-indoloctena kiselina. Kao ostale potrebne komponente za Ugijevu reakciju odabrani su paraformaldehid, benzilamin i 4-(2-izocijanoetil)morfolin. Istraženi su uvjeti za sintezu klasičnim postupkom, mehanokemijskom sintezom i sintezom uz mikrovalno zračenje. Reakcije su praćene tankoslojnom kromatografijom, produkt pročišćen kromatografijom na stupcu silikagela, a struktura spojeva potvrđena infracrvenom spektroskopijom, 1D i 2D spektroskopijom nuklearne magnetske rezonancije te spektrometrijom masa. Pripravljenim spojevima izmjeren je inhibitorni potencijal (korištenjem Ellmanove metode) prema enzimu butirilkolinesterazi (EC 3.1.1.8.) izoliranoj iz konjskog seruma. Dobivene su IC50 vrijednosti u rasponu od 10 do 270 μmol dm–3.

Abstract (english)

This thesis describes preparation of peptidomimetics by Ugi reaction, which has not been described in the literature so far. For the synthesis of a certain α-acylamino-amide, the carboxyl component was varied: benzoic acid, 3-bromobenzoic acid, 3-chlorobenzoic acid, 3-nitrobenzoic acid, acetic acid and 3-indolacetic acid. Other used components were: paraformaldehyde, benzylamine and 4-(2-isocyanoethyl)morpholine. The best reaction conditions were determined for the classical methods of organic synthesis, mechanochemical synthesis and microwave-assisted synthesis. The reactions were monitored by thin-layer chromatography and purified by column chromatography. The structures of compounds were confirmed by infrared spectroscopy, 1D and 2D nuclear magnetic resonance spectroscopy and mass spectrometry. The inhibitory activity of all prepared compounds toward the enzyme butyrylcholinesterase (EC 3.1.1.8.) isolated from horse serum was also measured using the Ellman method. IC50 values were found to be in range from 10 to 270 μmol dm–3.

• Keywords: peptidomimetici; Ugijeva reakcija; mikrovalna sinteza; butirilkolinesteraza; inhibitori
• Keywords (english): peptidomimetics; Ugi reaction; microwave-assisted synthesis; butyrylcholinesterase; enzyme inhibitors
• Language: croatian
• URN:NBN: urn:nbn:hr:217:352247
• Study programme: Title: Graduate university studies in chemistry; specializations in: Graduate university studies in chemistry; Course: Graduate university studies in chemistry; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra kemije (sveučilišni/a magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-02-23
• Created on: 2024-03-13 13:48:29