Biological activity-informed synthesis of quinoline-derived chiral γ-nitroketones via a bifunctional squaramide

Abstract Chiral γ-nitroketone-derived pyrrolidine N -oxide ( III ) exhibited potent in vitro anti-tumor activity against three cancer cell lines: human breast carcinoma (MDA-MB-231), human colorectal carcinoma (SW-480), and murine colorectal carcinoma (CT-26), with IC 50 values of 8.81 ± 0.12 μM, 9.07 ± 0.31 μM, and 5.68 ± 0.10 μM, respectively. Informed by the findings, a series of quinoline-derived chiral γ-nitroketones were synthesized via an efficient organocatalytic asymmetric strategy, achieving excellent yields (up to 99 %) and enantioselectivities (up to 99 % ee). This synthetic strategy involves enantioselective Michael additions between nitroalkanes and 2-enoylquinolines, catalyzed by a bifunctional squaramide under solvent-free conditions.