Synthesis of quinoline and harmine conjugates with potential antimalarial activity

U okviru ovog rada provedena je sinteza novih potencijalno biološki aktivnih hibrida kinolina, kumarina i harmina regioselektivnom 1,3-dipolarnom cikloadicijom terminalnih alkina i organskih azida. Spojevi su priređeni konvencionalnom sintetskom metodom koja zadovoljava većinu uvjeta ,,klik“ kemije. Harmin 1 prevodi se u reakciji s propargil-bromidom u 9-(prop-2-inil)harmin 2 koji onda Huisgenovom cikloadicijom s kumarinskim 3 i kinolinskim azidom 4 kataliziranom bakrom(I) daje odgovarajuće 1,2,3-triazolne konjugate 5 i 6. Polazni alkini 8 i 11 za sintezu kumarinskih i kinolinskih 1,2,3-triazola 7-(prop-2-iniloksi)harmina 9, 10 i 9-(prop-2-inil)-7-(prop-2-iniloksi)harmina 12, 13 dobivaju se iz harmola 7. Priređenim spojevima 5, 6, 9, 10, 12 i 13 ispitat će se antimalarijska aktivnost.The aim of this work was the synthesis of novel hybrids containing coumarine, quinoline and harmine moiety with potential biological activity, using regioselective 1,3-dipolar cycloaddition of terminal alkynes and organic azides. Novel compounds were prepared by conventional synthetic approach which fulfills most of ,,click“ chemistry requirements. Harmine 1 is converted with propargyl-bromide to 9-(prop-2-ynyl)harmine 2 which then in Huisgen copper(I) catalyzed cycloaddition with coumarine 3 and quinoline 4 azide gives corresponding 1,2,3-triazole conjugates 5 and 6. Alkynes 8 and 11 needed for the synthesis of coumarine and quinoline 1,2,3-triazoles 7-(prop-2-ynyloxy)harmines 9, 10 and 9-(prop-2-ynyl)-7-(prop-2-ynyloxy)harmines 12, 13 are synthesized starting from harmole 7. Antimalarial activity of prepared compounds 5, 6, 9, 10, 12 and 13 will be performed