Sinteza i karakterizacija novih amidnih derivata itakonske kiseline

master's thesis

• Title (english): Synthesis and characterization of novel itaconic acid amide
• Author: Vedran Katušić
• Mentor: Ivana Perković (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Davor Šakić (član povjerenstva)
• Committee member: Maja Beus (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2020-12-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Itakonska kiselina u svojoj strukturi posjeduje α,β konjugirane nezasićene veze što je čini Michaelovim akceptorom u reakcijama Michaelove adicije. Takvi spojevi se mogu ireverzibilno vezati na nukleofile u biološkim makromolekulama te na taj način inhibirati njihovu aktivnost. U ovom radu sintetizirano je osam novih derivata metilnog estera itakonske kiseline, 3a-h. Derivati 3a-f dobiveni su iz kiselinskog klorida monometil itakonata 2 u reakciji s odgovarajućim aminom. Derivati 3g i 3h dobiveni su metodom HATU couplinga uz DIEA kao bazu.
Svim sintetiziranim spojevima struktura je potvrđena uobičajenim analitičkim i spektroskopskim metodama (IR, 1H i 13C NMR, MS), a krutinama je određeno talište. Za sve spojeve računalno su predviđena fizikalno-kemijska svojstva i neka farmakokinetička svojstva. In vitro antitumorska aktivnost protiv različitih staničnih linija karcinoma i antivirusna aktivnost biti će ispitana u daljnjim istraživanjima na Zavodu za farmaceutsku kemiju Farmaceutsko biokemijskog fakulteta Sveučilišta u Zagrebu..

Abstract (english)

Itaconic acid has α,β conjugated bonds in its structure, which makes it an Michael acceptor in Michaels addition reactions. Michael acceptors can irreversibly bind to nucleophiles in biological macromolecules and irreversibly inhibit their activity. In this thesis eight novel derivatives of itaconic acid, 3a-h were synthesized. Derivatives 3a-f were obtained from the acyl chloride of monomethyl itaconate (2) in the reaction with the corresponding amine. Derivatives 3g and 3h were obtained using the standard HATU coupling method in the presence of DIEA as a base.
Structures of the newly synthesized compounds were confirmed by usual analytical and spectroscopic methods (IR, 1H and 13C NMR, MS) and melting points were determined for solids. Some physicochemical and some pharmacokinetic proprieties were calculated for the final products using computational methods. In vitro antitumor and antiviral activity will be explored in the contiuation of this research.

• Keywords: Michaelov akceptor; itakonska kiselina; amidi; sinteza
• Keywords (english): Michael acceptor; itaconic acid; amides; synthesis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:637560
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-27 11:47:19