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

Lingkai Kong; Jieru Meng; Wenyue Tian; Jiazheng Liu; Xueping Hu; Zhi-Hong Jiang; Wei Zhang; Yanzhong Li; Li-Ping Bai

doi:10.1021/acsomega.1c06017

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

ACS Omega. 2021 Dec 21;7(1):1380-1394. doi: 10.1021/acsomega.1c06017. eCollection 2022 Jan 11.

Authors

Lingkai Kong^{1

2}, Jieru Meng¹, Wenyue Tian¹, Jiazheng Liu¹, Xueping Hu², Zhi-Hong Jiang¹, Wei Zhang¹, Yanzhong Li³, Li-Ping Bai¹

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau University of Science and Technology, Taipa 999078, Macau, People's Republic of China.
² School of Chemistry and Chemical Engineering, Linyi University, Linyi, Shandong 276000, People's Republic of China.
³ School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China.

Abstract

An efficient approach for the synthesis of 1,2-diaryl diketones was developed from readily available α-methylene ketones by catalysis of I₂. 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 μM, 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 μM.