I2-Catalyzed Carbonylation of α-Methylene Ketones to Synthesize 1,2-Diaryl Diketones and Antiviral Quinoxalines in One Pot

An efficient approach for the synthesis of 1,2-diaryl diketones was developed from readily available alpha-methylene ketones by catalysis of I-2. In the same oxidation system, a novel one-pot procedure was established for the construction of antiviral and anticancer quinoxalines. The reactions proceeded well with a wide variety of substrates and good functional group tolerance, affording desired compounds in moderate to excellent yields. Quinoxalines 4ca and 4ad inhibited viral entry of SARS-CoV-2 spike pseudoviruses into HEK-293T-ACE2(h) host cells as dual blockers of both human ACE2 receptor and viral spike RBD with IC50 values of 19.70 and 21.28 mu M, respectively. In addition, cytotoxic evaluation revealed that 4aa, 4ba, 4ia, and 4ab suppressed four cancer cells with IC50 values ranging from 6.25 to 28.55 mu M.

Automated summary

An efficient approach for the synthesis of 1,2-diaryl diketones was developed from readily available alpha-methylene ketones by catalysis of I-2. In the same oxidation system, a novel one-pot procedure was established for the construction of antiviral and anticancer quinoxalines, showing good functional group tolerance with moderate to excellent yields. The synthesized compounds exhibited inhibitory effects on viral entry and cytotoxicity against cancer cells.