Analiza tetrahidrofurfurilnog derivata 3-makrozona i komponenata reakcijske smjese primjenom sustava LC-SPE/NMR

master's thesis

• Title (english): The analysis of tetrahydrofurfuryl 3-macrozone derivative and reaction mixture components using the LC-SPE/NMR
• Author: Lucia Ema Sekula
• Mentor: Predrag Novak (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Committee member: Mirta Rubčić (član povjerenstva)
• Committee member: Tomislav Jednačak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrozoni čine novu klasu spojeva nastalih konjugacijom azitromicina i derivata tiosemikarbazona koji su pokazali izvrsno antibakterijsko djelovanje in vitro na odabrane Gram-pozitivne i Gram-negativne bakterije. Velik porast rezistencije bakterija na postojeće antibiotike postao je globalni zdravstveni problem, pa je potreba za razvojem novih antibiotika jedan od glavnih ciljeva suvremene medicinske i farmaceutske kemije. Učinkovito i brzo pročišćavanje te izolacija novosintetiziranih bioaktivnih spojeva važan je korak u procesu sinteze koji prethodi biološkom testiranju novih molekula. Također, izolacija i karakterizacija onečišćenja važan je korak razvoja lijekova u farmaceutskoj industriji. Preparativna i semi-preparativna tekućinska kromatografija su klasične tehnike pročišćavanja spojeva koje iziskuju mnogo vremena i veliku količinu otapala. S ciljem smanjenja trajanja analize i utroška otapala, novosintetizirane spojeve moguće je analizirati vezanim sustavima. U ovom je radu uspješno provedena izolacija i strukturna karakterizacija novosintetiziranog bioaktivnog tetrahidrofurfurilnog derivata 3-makrozona i nekih onečišćenja iz reakcijske smjese primjenom vezanog sustava LC-SPE/NMR. Strukture izoliranih spojeva predložene su na temelju analize jedno- i dvodimenzijskih spektara NMR te spektara MS. U radu su raspravljene glavne prednosti ovog pristupa u usporedbi s klasičnim tehnikama off-line.

Abstract (english)

Macrozones are novel bioactive conjugates of azithromycin and thiosemicarbazones that possess very good in vitro antibacterial activity against selected Gram-positive and Gram-negative bacteria. Due to a global problem of growing bacterial resistance, development of new antibiotics and understanding of resistance mechanisms is of an outmost importance for modern medicine and pharmaceutical chemistry. Efficient and rapid purification and isolation of newly synthesized bioactive compounds is a crucial step prior to biological evaluation. Furthermore, isolation and identification of impurities is important during the drug development process in the pharmaceutical industry. Preparative and semi-preparative liquid chromatography are classical, but time- and solvent-consuming purification methods. Using hyphenated systems enables shorter analysis time and reduces solvent consumption. In this study successful isolation and structural characterization of newly synthesized tetrahydrofurfuryl 3-macrozone derivative and some impurities from reaction mixture have been performed using the LC-SPE/NMR approach. Structures of the isolated compounds were proposed on the basis of the analyzed one- and two-dimensional NMR spectra and MS spectra, respectively. The main advantages of the LC-SPE/NMR approach over classical off-line techniques are discussed.

• Keywords: azitromicin; LC-SPE/NMR; makrolidni antibiotici; makrozoni; profil onečišćenja; vezani sustavi
• Keywords (english): azithromycin; hyphenated system; impurity profiling; LC-SPE/NMR; macrozone; macrolide antibiotic
• Language: croatian
• URN:NBN: urn:nbn:hr:217:086883
• Project: Number: IP-2018-01-8098; Title: Makrozoni, novi konjugati makrolidnih antibiotika: Dizajn, priprava i interakcije; Title: Macrozones, New Conjugates of Macrolide Antibiotics: Design, Synthesis and Interactions; Acronym: Makrozoni/Macrozones; Leader: Predrag Novak; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-08-25 11:42:16