4-Glycosyloxyquinolines: Synthesis, Structural Characterization and Evaluation of Cytotoxic Activity

New 4-(β-D-glycosyloxy)quinolines were synthesized by Koenigs-Knorr reaction of quinolin-4(1H)-ones 1a-e with per-O-acetylated galactopyranosyl bromides or per-O-acetylated glucopyranosyl bromides, using silver carbonate as base and silver triflate as a promoter/activator in dry dichloromethane. Under these conditions, quinolin-4(1H)-ones tautomerize to the isomers 4-hydroxyquinolines, to a high extent, which after O-glycosylation gave quinolines 2a-d in 58-74% yields. However, under these conditions, C-3 substituted quinolin-4(1H)-ones 1e-h gave only a vestigial amount of product (2e) or did not react at all, probably due to steric hindrance and/or repulsive forces between the sugar unit and 3-substituent. Then, quinolines 2a-d were deacetylated, in mild conditions, using Amberlite IRA-400(OH) in methanol, yielding the corresponding deprotected 4-(β-D-glycosyloxy)quinolines in 70-88 % yields. The structures of the new synthesized compounds were assigned by 1D (1H and 13C) and 2D (HSQC, HMBC, and NOESY) NMR experiments, as well as by mass spectrometry (ESI+) and high-resolution mass spectrometry (HRMS). LogP values were calculated to assess the influence of glycosylation and acetyl protection on the compounds’ lipophilicity, providing insight into their potential membrane permeability and biological activity. The cytotoxicity of both tetraacetyl-protected and the deprotected 4-(β-D-glycosyloxy)quinolines 2a-e and 3a-d against non-small cell lung cancer cell (A549), and human neuroblastoma cell (SH-SY5Y) lines, was evaluated.