Quinoline-type compounds : asymmetric catalytic reaction and their biological activities

Abstract

The dipyridinyl phosphine ligand P-Phos was proven to be effective for many catalytic reactions. Herein the iridium-complex catalyzed asymmetric hydrogenation of 8-hydroxyquinoline substrates with the newly synthesized dipyridinyl phosphine type ligands was investigated. The electronic properties of the dipyridinyl phosphine type ligands had a significant effect on the enantioselectivities of 8-substituted 1,2,3,4-tetrahydroquinoline compounds. High enantioselectivities were observed for most 8-substituted quinoline compounds with ligands containing the electron-donating OMe group at the para-position with ee up to 96%. However, lower enantioselectivities were obtained with ligands containing the electron-withdrawing CF3 group at the para-position. Asymmetric transfer hydrogenation could be an alternative method to produce optically active compounds. In this project, the efficiency of easily synthesized chiral quinoline-based ligand 1-((1R,2R)-2-aminocyclohexyl)-3-(quinolin-8-yl)urea has been evaluated in the ruthenium catalyzed asymmetric transfer hydrogenation of aromatic ketones in isopropanol with ee up to 84%. This catalyst could be recovered and reused in room temperature ionic liquid and polyethylene glycol at least five times with no significant loss of enantioselectivities. The quinoline derivatives and their possible cytotoxic potential towards human cancer cell lines were described in this project. 8-Hydroxy-2-quinolinecarbaldehyde, 2-methyl-1,2,3,4-tetrahydroquinolin-8-ol, 2-methyl-8-(4-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydroquinoline, and 5,7-dibromo-2-methyl-1,2,3,4-tetrahydroquinolin-8-ol showed the best in vitro cytotoxicity against a plane of human cancer cell lines that include MDA231, T-47D, Hs578t, SaoS2, K562, SKHep, Hep3B, KYSE150, HKESC-3, HKESC-4 and MCF-7 with MTS50 range of 3.1-12.5{471}g/ml. The experimental results showed that these quinoline compounds were potential anti-tumor agents. Further in vivo results showed that the dosage of 5-10mg/kg/day (i.p. injection for 9 to 20 days) could completely abolish the growth of the Hep3B hepatocellular and KYSE150 esophageal tumor xenograft on athymic nude mice model compared with the control, with no damage to vital organs at the histological level.