Synthesis of arylphosphinoyl-functionalized dihydroisoquinolines by Reissert-type reaction and their biological evaluation

An efficient synthetic method for potentially biologically active new arylphosphinoyl-functionalized dihydroisoquinoline derivatives was developed by the Reissert-type reaction of isoquinoline, dialkyl acetylenedicarboxylates and secondary phosphine oxides or ethyl phenyl-H-phosphinate. The model reaction of isoquinoline, diethyl acetylenedicarboxylate and diphenylphosphine oxide was optimized in respect of the solvent, the temperature and the reaction time, as well as the dosing order of the starting materials. The protocol developed enabled the preparation of the target derivatives under mild conditions for a short reaction time. The in vitro cytotoxicity on different cell lines and the antibacterial effect of the phosphorylated dihydroisoquinolines synthesized were also investigated. Based on the IC50 values determined, the derivatives, which contain 3,5-dimethylphenyl or 2-naphtyl groups on the phosphorus atom, showed a promising activity against human promyelocytic leukemia (HL-60) cells and against Bacillus Subtilis Gram-positive bacteria.