Organometalna sinteza novih derivata hidroksikumarina s potencijalnim antioksidativnim i citostatskim djelovanjem

master's thesis

• Title (english): Organometallic synthesis of novel hydroxycoumarin derivatives with potential antioxidant and cytostatic activity
• Author: Mateja Toma
• Mentor: Tatjana Gazivoda Kraljević (mentor)
• Committee member: Tatjana Gazivoda Kraljević (predsjednik povjerenstva)
• Committee member: Silvana Raić-Malić (član povjerenstva)
• Committee member: Svjetlana Krištafor (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2016-07-07, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Organic Chemistry

Abstract

U ovom radu prikazana je sinteza, spektroskopska karakterizacija i in silico analiza derivata kumarina supstituiranih u položaju 3 ariletinilnim (1-3), alkiletinilnim (4-7), arilnim (11-14) ili 1,2,3-triazolnim supstituentima (21-24) te 3-azido kumarinskih derivata (18-20). Sonogashira-inom reakcijom 7-hidroksi-3-klor-4-metilkumarina s odgovarajućim arilnim ili alkilnim terminalnim alkinima uz Pd-katalizator sintetizirani su derivati kumarina supstituirani u položaju 3 (1-7) ariletinilnim ili alkinilnim supstituentima. Uvođenje aromatskog prstena u položaj 3 kumarinske jezgre provedeno je Suzuki-jevom reakcijom 7- hidroksi-3-klor-4-metilkumarina s odgovarajućim arilbornim kiselinama pri čemu su pripravljeni spojevi 11-14. Prekursori 16 i 17 za Perkinovu sintezu kumarinskog prstena sintetizirani su Sonogashira-inom reakcijom koji su potom višestupnjevitom sintezom in situ prevedeni u 3-azidokumarinske derivate 19 i 20. 3-Azido-7-hidroksikumarin 18 pripravljen je višestupnjevitom reakcijom, koja u prvom stupnju uključuje Perkinovu ciklizaciju. 1,2,3- triazolni supstituent u položaj 3 kumarina uveden je "klik" reakcijama potpomognutim mikrovalovima s odgovarajućim terminalnim alkinima uz Cu katalizator pri čemu su sintetizirani spojevi 21-24. Strukturna i spektroskopska karakterizacija spojeva provedena je 1H NMR, UV/Vis i fluorimetrijskom spektroskopijom. Farmakološka aktivnost i moguće biološke mete novopripravljenih spojeva predviđene su in silico analizom (PASS).

Abstract (english)

This paper describes synthesis, spectroscopic characterization and in silico analysis of coumarin derivatives substituted with arylethynyl (1-3), alkylethynyl (4-7), aryl (11-14) or 1,2,3-triazole substituents at position 3 and 3-azido coumarin derivatives (18-20). Coumarin derivatives substituted in position 3 (1-7) with alkynyl- or arylethynyl- substituents were synthesized by Sonogashira cross-coupling reaction of 3-chloro-7-hydroxy-4-methylcoumarin with an appropriate aryl- or alkyl- terminal alkynes using palladium as catalyst. Introduction of an aromatic ring at position 3 of the coumarin moiety was carried out by Suzuki reaction of 3-chloro-7-hydroxy-4-methylcoumarin with corresponding arylboronic acids and compounds 11-14 were synthesized. Precursors 16 and 17 used for Perkin coumarin ring synthesis were prepared by Sonogashira reaction and by multi-step synthesys in situ converted into 3- azidocoumarin derivatives 19 and 20. 3-Azido-7-hydroxycoumarin 18 was also prepared by multi-step synthesys, which included Perkin cyclization in the first step. 1,2,3-triazole ring was introduced at position 3 of coumarin moiety by microwave assisted "click" reaction with appropriate terminal alkyne using copper catalyst which gave compounds 21-24. Structural and spectroscopic characterization of novel compounds was performed by 1H NMR, UV / Vis and fluorimetric spectroscopy. Pharmacological activity and possible biological targets of novel compounds were provided by in silico analysis (PASS).

• Keywords: derivati 7-hidroksi-4-metilkumarina; 1 2 3-triazol; Sonogashira-ina reakcija unakrsnog povezivanja; Suzuki-jeva reakcija unakrsnog povezivanja; "klik" reakcija; Perkinova reakcija
• Keywords (english): 7-hydroxy-4-methylcoumarin derivatives; 1 2 3-triazole; Sonogashira crosscoupling reaction; Suzuki reaction; "click" reaction; Perkin reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:149:028408
• 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: 2017-04-20 08:18:16