Sinteza novih C6-supstituiranih purinskih derivata Pd-kataliziranim reakcijama unakrsnog spajanja

master's thesis

• Title (english): Synthesis of novel C6-substituted purine derivatives using Pd-catalyzed cross-coupling reactions
• Author: Doria Curiš
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Danijela Ašperger (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je sinteza novih C6-supstituiranih purinskih derivata Pd-kataliziranim reakcijama unakrsnog spajanja. N-9 propargilirani derivati purina 1a i 1b priređeni su reakcijom N-alkiliranja. Odgovarajući aldoksim 3 potreban za sintezu izoksazolnih derivata priređen je reakcijom kloriranja piridin-2-aldoksima 2. Novi 2,3-disupstituirani purinski izoksazoli 4a i 4b priređeni su bazno-kataliziranom 1,3-dipolarnom cikloadicijom iz N-9 propargiliranih derivata purina 1a i 1b te kloriranog aldoksima 3. Dobiveni 2,3-disupstituirani purinski izoksazoli 4a i 4b supstituirani su u položaju C-6 uporabom paladij-katalizirane Suzuki-Miyaurine i Sonogashirine reakcije unakrsnog povezivanja. Na taj su način uspješno sintetizirani C6-supstituirani izoksazolni derivati purina 5a, 5b i 6a–d. Nadalje, odabrani
C6-supstituirani izoksazolni derivati purina 5a, 5b i 6b korišteni su kao ligandi za sintezu renij(I) trikarbonilnih kompleksa 7a, 7b i 8. Strukture novosintetiziranih spojeva potvrđene su spektroskopijom 1H i 13C NMR te UV/Vis i IR-spektroskopijom. Antitumorska ispitivanja novosintetiziranih spojeva su u tijeku.

Abstract (english)

In this work the synthesis of novel C6-substituted purine derivatives using Pd-catalyzed cross-coupling reactions is described. N-9 propargylated purine derivatives 1a and 1b were prepared by N-alkylation. The corresponding aldoxime 3 for the synthesis of isoxazole derivatives was synthesized by the chlorination reaction of pyridine-2-aldoxime 2. A novel 2,3-disubstituted purine isoxazole derivatives 4a and 4b were prepared by base-catalyzed 1,3-dipolar cycloaddition of N-9 propargylated purine derivatives 1a and 1b and chlorinated oxime 3. Synthesized 2,3-disubstituted purine-isoxazole derivatives 4a and 4b were functionalized at C-6 position using Pd-catalyzed Suzuki-Miyaura and Sonogashira cross-coupling reaction and so C6-substituted purine-isoxazole derivatives 5a, 5b and 6a–d were synthesized. Selected C6-substituted purine-isoxazole derivatives 5a, 5b and 6b were also used as ligands for the synthesis of rhenium(I) tricarbonyl complexes 7a, 7b and 8.
The structures of all compounds were determined by 1H NMR and 13C NMR spectroscopy as well as by UV/Vis and IR spectroscopy. Anticancer evaluations of novel compounds are in progress.

• Keywords: purin; izoksazol; Pd-katalizirane reakcije unakrsnog povezivanja; metalni kompleksi
• Keywords (english): purine; isoxazole; Pd-catalyzed cross-coupling reactions; metal complexes
• Language: croatian
• URN:NBN: urn:nbn:hr:149:926794
• 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: Materials Science and Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-09-01
• Created on: 2023-11-24 11:06:45