Synthesis and spectroscopic characterization of novel amino-substituted tetracyclic imidazo[4,5-b]piridyne derivatives

U ovom radu prikazana je sinteza i spektroskopska karakterizacija novih amino supstituiranih tetracikličkih derivata imidazo[4,5-b]piridina. Brojna istaživanja pokazala su da derivati imidazo[4,5-b]piridina imaju širok spektar biološkog djelovanja, a upravo tetraciklički derivati pokazali su antitumorsko djelovanje. Za pripravu ciljanih molekula korištene su klasične metode organske kemije, dok je posljednji stupanj sinteze potpomognut mikrovalnim zračanjem. Kondenzacijom derivata imidazo[4,5-b]piridina 3 s 2-klorbenzoil-kloridom ili 4-fluor- 2-klorbenzoil-kloridom, priređeni su aciklički prekursori 5 i 19. Termičkom ciklizacijom priređena je smjesa cikličkih regioizomera 6a i 6b te 20a i 20b iz kojih su dobiveni 5-klor supstituirani tetraciklički derivati 9 i 10 te 2-fluor-5-klor supstituirani derivati 21 i 22. Amino i diamino supstituirani regioizomeri 9-16 i 24-28 i 30 priređeni su nekataliziranom reakcijom aminacije potpomognutom mikrovalovima. Strukture priređenih spojeva potvrđene su 1H i 13C NMR spektroskopijom, a struktura regioizomera utvrđena je 2D NMR spektroskopskim tehnikama. Odabrani derivati 11, 15, 25 i 29 okarakterizirani su UV/Vis i fluorimetrijskom spektroskopijom.Within this work, the synthesis and spectroscopic characterization of novel aminosubstituted tetracyclic imidazo[4,5-b]pyridine derivatives was presented. According to previous research, imidazo[4,5-b]pyridine derivatives have a broad spectrum of biological activities and tetracyclic derivatives showed potent antitumour activity. For the synthesis of novel targeted compounds, classical organic synthesis reactions as well as microwave assisted synthesis were used. Due to the condensation of imidazo[4,5-b]pyridine derivative with 2-chlorobenzoyl chloride or 4-fluoro-2-chlorobenzoyl chloride, acyclic precursors 5 and 19 were prepared. In reaction of termic cyclization, the mixture of cyclic regioisomers 6a and 6b or 20a and 20b was prepared. Furthermore, from 6a and 6b, or 20a and 20b, 5-chloro (7 and 8) and 2-fluoro- 5-chloro- (21 and 22) substituted tetracyclic derivatives were obtained in the next step. Amino substituted 9 – 16 and diamino substituted 24 – 28 and 30 regioisomers were prepared by uncatalyzed microwave assisted amination. Structures of newly prepared compounds were confirmed by means of 1H and 13C NMR spectroscopy. Structure of regioisomers was determined by 2D NMR spectroscopy. Spectroscopic characterization of derivatives 11, 15, 25 and 29 was performed by using UV/Vis and fluorimetric spectroscopy in methanol