Regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles

Cilj ovog rada bila je sinteza novih 1,4-disupstituiranih 1,2,3-triazolnih derivata s 7-deazapurinom i 7-hidroksikumarinom kao potencijalnih biološki aktivnih spojeva. Azidni derivat 6-klor-7-deazapurina 2, kao ključni prekursor, pripravljen je iz N-brometilnog derivata 7-deazapurina 1. Derivati 6-klor-7-deazapurina i 1,2,3-triazola (3 - 13) međusobno povezanih etinilnom premosnicom pripravljeni su ”click” reakcijom potpomognutom mikrovalovima organskog azida i terminalnih alikina kataliziranom bakrom. Nadalje, Huisgenovom 1,3-dipolarnom cikloadicijom pripravljeni su derivati 1,2,3-triazola i 7-hidroksikumarina (14 - 17) iz kumarinskog azida i odgovarajućih terminalnih alkina. Strukture svih pripravljenih spojeva potvrđene su 1H i 13C NMR spektroskopijom. Provedena su ispitivanja antibakterijskog djelovanja spojeva 14 - 17 na osam bakterijskih vrsta (četiri Gram-pozitivne i četiri Gram-negativne beakterijske vrste). Spojevi 16 i 17 pokazali su bolju učinkovitost na Gram-pozitivne bakterije Enterococcus faecali od antibiotika ceftazidima (CAZ) i ciprofloksacina (CIP).The aim of this work was the synthesis of novel 1,4-disubstituted 1,2,3-triazole derivatives of 7-deazapurine and coumarin as potential biologically active compounds. The organic azide of 6-chloro-7-deazapurine, as a key precursor, was prepared from N-bromoethynyl derivative of the 7-deazapurine 1. Derivatives of 6-chloro-7-deazapurine and 1,2,3-triazole (3 - 13) bound via ethynyl linker were prepared by copper catalyzed "click" chemistry approach under microwave irradiation between organic azides and terminal alkynyl. Furthermore, derivatives of 1,2,3-triazole and 7-hydroxycoumarin (14 - 17) were prepared by Huisgen 1,3-dipolar cycloadition from the coumarin azide and corresponding terminal alkynes. The structures of all synthesized compounds were confirmed by 1H i 13C NMR spectroscopy. The anti-bacterial activity of the synthesized compounds 14 - 17 was performed in vitro against four Gram-positive bacterial species and four Gram-negative bacterial species. The MIC values of the tested compounds compared with those of ceftazidime and ciprofloxacine. Compounds 16 and 17 have shown anti-bacterial activity, which was higher than ceftazidime against Gram-negative bacteria Enterococcus faecali