Synthesis of new 7-substituted thiazolo {4,5-d} pyrimidine derivatives : diploma thesis

Prirodni analozi tiazolo [4,5-d] pirimidina su purinske baze i njihovi derivati koji su prisutni u nukleinskim kiselinama, nekim vitaminima i koenzimima. Derivati tiazolo [4,5-d] pirimidina postaju sve važniji kako se širi i njihov spektar djelovanja u medicini. Opisane su neke osnovne strukture koje su pokazale terapeutsku aktivnost. U ovom radu provedena je sinteza 11 novih derivata tiazolo [4,5-d] pirimidina u svrhu razvijanja novih biološki aktivnih spojeva. Reakciji sinteze konačnih novih derivata prethodilo je 5 reakcija. Najprije je provedena reakcija sinteze cijanoacetamida, uslijedila je reakcija aktivnih metilenskih nitrila sa sumporom i fenilizotiocijanatom, a zatim reakcije ciklokondenzacije prilikom kojih dolazi do zatvaranja drugog prstena i postiže se prepoznatljiva biciklička struktura. Reakcije ciklokondenzacije provedene su s dva različita aromatska aldehida (benzaldehid i 4-fluorbenzaldehid) te su dobiveni različiti produkti koji su korišteni za daljnje sinteze čime se sintetski put razdijelio na dva paralelna sintetska puta. Slijedile su reakcije kloriranja prilikom kojih se atom kisika zamjenjuje atomom klora na poziciji 7, reakcije s hidrazinom prilikom kojih se na poziciji 7 atom klora zamjenjuje hidrazinskom skupinom te konačno, reakcije aciliranja kod kojih dolazi do nukleofilne supstitucije na primarnom aminu hidrazinske skupine s reaktantima poput različitih acil-klorida/bromida ili anhidrida. U svrhu praćenja sinteze korištena je tankoslojna kromatografija (TLC). Za analizu sintetiziranih spojeva u svrhu potvrde dobivene strukture korištene su različite tehnike i to: tehnika elementarne analize, masena spektrometrija, infracrvena spektroskopija te nuklearna magnetska rezonantna spektroskopija ( 1 H-NMR, 13 C-NMR).The natural analogues of thiazolo [4,5-d] pyrimidines are purine bases and their derivatives which are present in nucleic acids, some vitamins and coenzymes. Thiazolo [4,5-d] pyrimidine derivatives became increasingly important as their spectrum of activity in medicine expands. Some basic structures that demonstrated therapeutic activity have been described. In this paper, the synthesis of 11 new thiazolo [4,5-d] pyrimidine derivatives was carried out in order to develop new biologically active compounds. The reaction of cyanoacetamide synthesis was carried out first followed by the reaction of active methylene nitriles with sulfur and phenyl isothiocyanate and then, using cyclocondensation reactions in which the second ring was closed, a recognizable bicyclic structure was achieved. The cyclocondensation reactions were carried out with two different aromatic aldehydes (benzaldehyde and 4- fluorobenzaldehyde) to produce two different products which were used for further synthesis and allowed the single synthetic pathway to be divided into two parallel synthetic pathways. Chlorination reactions followed in which the oxygen atom was replaced by a chlorine atom at position 7, a hydrazine reaction at which a chlorine atom is replaced by a hydrazine moiety and finally, by the acylation reaction in which nucleophilic substitution occurs on the primary amine of the hydrazine group with reactants such as different acyl chloride / bromide or anhydride. Thin layer chromatography (TLC) was used to monitor the synthesis. Different techniques were used for the analysis of synthesized compounds for the purpose of confirming the structure obtained: elemental analysis technique, mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectroscopy ( 1 H-NMR, 13 C-NMR)