The novel coumarin derivatives: synthesis using Pd-catalysed and "click" reactions, spectroscopic properties and antitumor activity

U ovom je radu prikazana sinteza, spektroskopska karakterizacija i in silico analiza C-3 supstituiranih 1,2,3-triazolnih i alkinilnih derivata kumarina (3-22). Početni spoj za „klik“ reakcije, 3-azido-7-hidroksikumarin (2) pripravljen je Perkinovom reakcijom. U položaj C-3 kumarinskog prstena uvedeni su 1,2,3-triazolni supstituenti mikrovalovima potpomognutim „klik“ reakcijama s odgovarajućim terminalnim alkinima uz Cu katalizator pri čemu su sintetizirani spojevi (3-20). Sonogashira-inom reakcijom unakrsnog povezivanja 7-hidroksi-3-klor-4-metilkumarina s odgovarajućim arilnim terminalnim alkinima uz katalizator Pd(PPh3)4 i CuI kao kokatalizator pripravljeni su 3-ariletinil-7-hidroksi-4-metil kumarini 21 i 22. „One-pot“ reakcijom 7-hidroksi-3-klor-4-metilkumarina, NaN3, L-prolina i NaOH nije sintetiziran 3-azido-7-hidroksi-4-metilkumarin koji je trebao poslužiti kao početni spoj za „klik“ reakcije. Strukturna i spektroskopska karakterizacija spojeva provedena je 1H NMR, UV/Vis i fluorimetrijskom spektroskopijom. In silico analizom (PASS) predviđene su farmakološke aktivnosti i moguće biološke mete novopripravljenih spojeva.This paper describes synthesis, spectroscopic characterization and in silico analysis of C-3 substituted 1,2,3-triazole and alkynyl coumarin derivatives (3-22). Starting compound for „click“ reactions, 3-azido-7-hydroxycoumarin (2) was prepared by Perkin reaction. In position C-3 of coumarin ring were introduced 1,2,3-triazole substituents with Cu-catalyzed „click“ reactions under microvawe irradiation with corresponding terminal alkynes whereby compounds (3-20) were synthesized. Compounds of 3-arylethynyl-7-hydroxy-4-methylcoumarin (21-22) were prepared by Sonogashira cross-coupling reaction with corresponding aryl terminal alkynes, catalyst Pd(PPh3)4 and cocatalyst CuI. „One-pot“ reaction with mixture of 7-hydroxy-3-chlor-4-methylcoumarin, NaN3, L-prolin and NaOH was not successful for synthesis starting compound for „click“ reactions, 3-azido-7-hydroxy-4-methylcoumarin. Structural and spectroscopic characterization of 1,2,3-triazole coumarin derivatives was conducted using 1H-NMR, UV/Vis and fluorescence spectroscopy. Pharmacological effects and possible biological targets for novel synthesized compounds were provided using in silico analysis (PASS)