Synthesis and characterization of amide type harmicenes

β-karbolinski alkaloidi predstavljaju veliku skupinu prirodnih i sintetskih spojeva. Široko su rasprostranjeni u prirodi te pokazuju širok spektar farmakoloških učinaka poput antimalarijskog, antimikrobnog i citostatskog. S druge strane, ferocen zbog svoje stabilnosti, slabe toksičnosti i oksidoredukcijskih svojstava čini idealnog partnera β-karbolinima u sintezi novih hibridnih spojeva, s obzirom da je dokazano da derivati ferocena pokazuju antimalarijsko i citostatsko djelovanje. U okviru ovog rada sintetizirana su četiri nova harmicena amidnog tipa, hibridna spoja β-karbolina harmina i ferocenoctene kiseline (6, 11, 15, 18) koji se razlikuju po položaju derivatizacije β-karbolinskog prstena (1, 3, 7 i 9). Prije sinteze hibridnih spojeva, za sintezu derivata u položajima 1 i 3 bilo je potrebno sintetizirati β-karbolinske prstenove 1 i 7 pomoću Pictet-Spenglerove reakcije, dok je za sintezu derivata u položajima 7 i 9 početni spoj bio harmin. U idućim reakcijama u molekulu β-karbolina bilo je potrebno uvesti primarnu amino skupinu, koja u reakciji povezivanja s ferocenoctenom kiselinom daje konačne spojeve, harmicene amidnog tipa. U reakciji povezivanja korišteni su standardni reagensi i uvjeti (HATU/DIEA/sobna temperatura). Sintetiziranim spojevima strukture su potvrđene standardnim analitičkim i spektroskopskim metodama (1H i 13C NMR, IR te MS), a usto su im određena i tališta. Biološki učinak sintetiziranih spojeva ispitat će se u budućim istraživanjima.Alkaloids of the β-carboline type represent a large group of natural and synthetic compounds. They are widely spread and display a wide array of pharmacological effects such as antimalarial, antimicrobial and cytostatic. On the other hand, ferrocene, owing to its stability, low toxicity and redox properties, is an ideal partner of β-carbolines in the synthesis of new hybrid compounds, since it has been shown that ferrocene derivatives exhibit antimalarial and cytostatic activities. Here we present synthesis of four new harmicenes of the amide type, i.e. hybrid compounds composed of β-carboline and ferrocene moieties linked via amide bond, in four different positions of the β-carboline ring (1, 3, 7 i 9) (6, 11, 15, 18). Before the synthesis of hybrid compounds in the positions 1 and 3, β-carbolines 1 and 7 were prepared by the means of Pictet-Spengler reaction, whereas harmine was the starting compound for the synthesis of harmicenes prepared in the positions 7 and 9 of the b-carboline ring. Further reactions included introduction of the primary amino group in the b-carboline moiety and coupling reaction with ferroceneacetic acid, by applying standard reagents and conditions (HATU/DIEA/room temperature). The structures of synthesized compounds were confirmed by standard analytical and spectroscopic methods (1H and 13C NMR, IR and MS), also their melting points were determined. Their biological activities will be evaluated in the future studies