Priprava i karakterizacija intermedijera C u sintezi lijeka eltrombopaga

master's thesis

• Title (english): Preparation and characterization of intermediate C in the synthesis of drug eltrombopag
• Author: Ema Zahirović
• Mentor: Jagoda Šušković (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Antibiotic, Enzyme, Probiotic and Starter Cultures Technology); Zagreb
• Defense date and country: 2016-09-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Eltrombopag je lijek koji pripada skupini trombopoetin receptor agonista i koristi se za liječenje kronične imunološke trombocitopenije. Cilj ovog rada bio je razviti proces za sintezu i izolaciju intermedijera C koje će se koristiti kao standard za tekućinsku kromatografiju visoke djelotvornosti (HPLC), pri određivanju kromatografske čistoće intermedijera C u sintezi lijeka eltrombopaga. Istražena je učinkovitost Raney nikal i natrijeva ditionita kao katalizatora na hidriranje spoja BPCA-4 (5'-kloro-2'-hidroksi-3'nitro-[1,1'-bifenil]-3-karboksilna kiselina) u svrhu odabira katalizatora kojim će se dobiti viši prinos i odgovarajuća kromatografska čistoća. Sinteza intermedijera C primjenom natrijevog ditionita kao katalizatora pokazala se kao neučinkovita metoda zbog nezadovoljavajuće kromatografske čistoće produkta (59,99 %) i malog prinosa (26,74 %). Raney nikal se pokazao učinkovitijim katalizatorom za sintezu intermedijera C pa su sva naredna istraživanja provedena s ovim katalizatorom. Uzorak ELTC-1612 može poslužiti kao standard za tekućinsku kromatografiju visoke djelotvornosti (HPLC) pri određivanju kromatografske čistoće tijekom industrijske sinteze lijeka eltrombopaga.

Abstract (english)

Drug eltrombopag is a thrombopoietin agonist receptor for the treatment of chronic immune thrombocytopenia. It is necessary to develop a process for the synthesis and isolation of intermediate C to be used as a standard for high performance liquid chromatography (HPLC) to determine the chromatographic purity of intermediate C in the synthesis of the drug eltrombopag. Efficiency of Raney nickel and sodium dithionite catalyst is tested on the hydrogenation compound BPCA-4 and the optimal catalyst is selected that produces a high yield of the corresponding chromatographic purity. Synthesis of intermediate C by using sodium dithionite as a catalyst proved to be an ineffective method due to unsatisfactory chromatographic product purity (59.99 %) and low yield (26.74 %). Raney nickel proved to be more efficient catalyst for the synthesis of intermediate C so all subsequent studies conducted with this catalyst. Sample ELTC-1612 can serve as a standard for high performance liquid chromatography (HPLC) for the determination of chromatographic purity for the industrial synthesis of the drug eltrombopag.

• Keywords: eltrombopag; intermedijer C; standard; HPLC; hidriranje
• Keywords (english): eltrombopag; intermediate C; standard; HPLC; hydrogenation
• Language: croatian
• URN:NBN: urn:nbn:hr:159:158852
• Study programme: Title: Bioprocess Engineering; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva (magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-25 13:46:23