Novi konjugati purina, purinskih bioizostera i ferocena

master's thesis

• Title (english): Novel purine, purine bioisosteres and ferrocene conjugates
• Author: Martina Piškor
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Silvija Maračić (član povjerenstva)
• Committee member: Danijela Ašperger (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Cilj ovog rada bila je sinteza novih konjugata purina, purinskih bioizostera i ferocena kao spojeva s potencijalnim antitumorskim djelovanjem. U tu svrhu sintetizirani su propargilirani derivati indola, 5-jodindola i benzimidazola (1 – 3) te azidi bromferocena, ferocenmetanola i ɑ-metil-ferocenmetanola (4 – 6). Reakcijom 1,3-dipolarne cikloadicije odgovarajućih azida (4 – 6) i terminalnih alkina (1 – 3) uz Cu(I), kao katalizator, prema načelima “klik“ kemije dobiveno je devet konjugata purina, purinskih bioizostera i ferocena 7 – 15. Nadalje, pripravljeni su azidi 6-klor-7-deazopurina, 6-pirolidin-7-deazopurina, 6-piperidin-7-deazapurina (17 – 19). Dobiveni azidni derivati purina reakcijom s terminalnim ferocenom dali su nove hibride purina i ferocena 20 – 22. Sintetizirani su, nadalje, azidi 6-klorpurina, 6-pirolidinpurina i 6-piperidinpurina (24, 28, 30) koji su u reakciji 1,3-dipolarne cikloadicije s terminalnim ferocenom uz Cu(I) kao katalizator dali tri nova spoja 31 – 33. Sintetizirano je ukupno petnaest novih konjugata purina, purinskih bioizostera i ferocena. Strukture spojeva dokazane su 1H- i 13C- NMR spektroskopijom. Biološka ispitivanja spojeva 7 – 15, 20 – 22 i 31 – 33 su u tijeku.

Abstract (english)

The aim of this work was the regioselective synthesis of novel conjugates of purine, purine bioisosteres and ferrocenes 7 – 15, 20 – 22, 31 – 33 with potential antitumor activity. For this purpose propargylated indole, 5-iodoindole and benzimidazole (1 – 3) and azides of bromoferrocene, ferrocene methanol and ɑ-methyl-ferrocene methanol (4 – 6) were synthesized. Triazole derivatives of ferrocene were then prepared using 1,3-dipolar cycloaddition reaction of the corresponding azide derivative (4 – 6) and terminal alkynes (1 – 3) with Cu(I), as a catalyst, following the concept of ´click´ chemistry. The azides of 6-chloro-7-deazopurine, 6-pyrrolidine-7-deazopurine, 6-piperidine-7-deazapurine (17 – 19) were also prepared. The azides were combined with terminal ferrocene and new purine and ferrocene conjugates were obtained 20 – 22. The azides of 6-chloropurine, 6-pyrrolidinpurine and 6-piperidinpurine were prepared (24, 28, 30) and the reaction of thus obtained azides with terminal ferrocene afforded new compounds 30 – 33. Reaction products were isolated and purified by column chromatography. The structures of all compounds have been confirmed by 1H and 13C NMR spectroscopy and the biological evaluations of 7 – 15, 20 – 22 i 31 – 33 are in progress.

• Keywords: purini; 7-deazapurini; feroceni; 1 2 3-triazoli; bakrom katalizirana 1 3-dipolarna cikloadicija; bioizosterija; antitumorska aktivnost
• Keywords (english): purine; 7-deazapurine; ferrocene; 1 2 3-triazoles; Cu-catalysed 1 3-dipolar cycloaddition; bioisosterism; antitumor activity
• Language: croatian
• URN:NBN: urn:nbn:hr:149:106513
• Project: Number: IP-2018-01-4682; Title: Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja; Acronym: PurBioCaPa; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• 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: Access restricted to students and staff of home institution
• Created on: 2022-02-26 22:11:00