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Pojava sve veće otpornosti bakterija na postojeće antibiotike predstavlja ozbiljan zdravstveni problem pa se stoga u području farmaceutske i medicinske kemije ulažu veliki napori u razvoj novih antibiotika. Makrozoni predstavljaju nove konjugate azitromicina i derivata tiosemikarbazida koji pokazuju izvrsnu antibakterijsku aktivnost in vitro na susceptibilne i rezistentne bakterijske sojeve. Proces razvoja novih antibiotika sastoji se od mnogo koraka, pri čemu je izuzetno važna identifikacija farmaceutskih onečišćenja i novosintetiziranih spojeva – potencijalnih antibiotika. U tu svrhu vrlo često se koriste vezani analitički sustavi pomoću kojih se postiže učinkovitije i brže pročišćavanje te identifikacija spojeva u odnosu na klasične tehnike off-line. U ovom diplomskom radu provedena je izolacija i strukturna karakterizacija novosintetiziranih 3-trifluormetoksifenil- i 3-(3-fenilpropil)-makrozona te njihovih dijastereomera, kao i nekih onečišćenja iz reakcijskih smjesa pomoću sustava LC-SPE/krioNMR. Za strukturnu karakterizaciju izoliranih komponenata korištene su jedno- i dvodimenzijske tehnike NMR te spektrometrija masa. Na temelju analize prikupljenih podataka predložene su strukture izoliranih spojeva. Increasing bacterial resistance to existing antibiotics is a serious health problem, and great efforts are being made to discover and develop new antibiotics to overcome this problem. Macrozones are novel conjugates of azithromycin and thiosemicarbazides that show very good in vitro activity against susceptible and resistant bacterial strains. Development of new antibiotics is a multistep process and one of the most important steps is the identification of pharmaceutical impurities and newly synthesized compounds – potential antibiotics. For this purpose, hyphenated systems are very oftenly used to achieve more efficient and faster purification and identification of compounds compared to off-line techniques. In this study, isolation and structural characterization of newly synthesized 3-trifluoromethoxyphenyl- and 3-(3-phenylpropyl)-macrozones and their diastereoisomers, as well as some impurities from reaction mixtures, have been performed using hyphenated system LC-SPE/cryo-NMR. Oneand two-dimensional NMR techniques and mass spectrometry were used for structural characterization of isolated components. Based on the analysis of collected data, the structures of isolated compounds were proposed. |
