The novel 5-azacytosine and6-azauracil derivatives: synthesis and structural characterization

U ovom radu prikazana je sinteza i strukturna karakterizacija novih derivata 5-azacitozina i 6-azauracila u svrhu ispitivanja njihovog biološkog djelovanja protiv tumorskih staničnih linija porijeklom iz čovjeka. N-3 propargilirani derivat 5-azacitozina (1) te N-1 propargilirani (5) i N,N-1,3 dipropargilirani derivati 6-azauracila (6) sintetizirani su reakcijom N-alkiliranja 5-azacitozina i 6-azauracila uz NaH kao bazu i propargil-bromid kao alkilirajući reagens. Reakcijom propargiliranih pirimidinskih derivata 1, 5 i 6 u uvjetima Huisgenove 1,3-dipolarne cikloadicije potpomognute mikrovalnim zračenjem s odgovarajućim aromatskim azidima uz bakar sintetizirani su 1,2,3-triazolilni derivati 5-azacitozina (24) i 6-azauracila (7 i 8). Reakcijom jodiranja N-1 propargiliranog derivata 6-azauracila (5) sintetiziran je N-1-(2-jod-prop-2-en)-6-azauracil (9). Strukture novosintetiziranih spojeva potvrđene su 1H NMR spektroskopijom.In this work the synthesis and structural characterization of new 5-azacytosine and 6-azauracil derivatives is described in order to determine their activities against human malignant tumor cell lines. N-3 propargylated 5-azacytosine derivative (1), N-1 propargylated (5) and N,N-3 dipropargylated 6-azauracil derivatives (6) were synthesized by N-alkylation of 5-azacytosine and 6-azauracil using propargyl bromide as alkylating reagent and NaH as base. Reaction of propargylated pyrimidine derivatives 1, 5 and 6 with corresponding azides by using microwave assisted Huisgen 1,3-dipolar cycloaddition conditions gave 1,2,3-triazole derivatives of 5-azacytosine (2-4) and 6-azauracil (7 and 8). N-1-(2-iodo-prop-2-ene)-6-azauracil (9) was sythesized by reaction of iodination of N-1 propargylated 6-azauracil derivative (5). The structures of newly synthesized compounds were confirmed by 1H NMR spectroscopy