Tricyclic Aza-Andrographolide Derivatives from Late-Stage Hydroamination and Their Anti-human Coronavirus (Anti-HCoV) Activity

Chao Che; Ding Jiang; Jiayin Zhang; Qi Xing; Ting Li; Yi Zhao; Liangyu Guan; Huangcan Chen; Dehu Xiang; Man Di; Zhendong Zhu

doi:10.1021/acsomega.2c02979

Tricyclic Aza-Andrographolide Derivatives from Late-Stage Hydroamination and Their Anti-human Coronavirus (Anti-HCoV) Activity

ACS Omega. 2022 Jul 7;7(28):24824-24837. doi: 10.1021/acsomega.2c02979. eCollection 2022 Jul 19.

Authors

Chao Che^{1

2}, Ding Jiang¹, Jiayin Zhang¹, Qi Xing¹, Ting Li¹, Yi Zhao¹, Liangyu Guan¹, Huangcan Chen¹, Dehu Xiang¹, Man Di¹, Zhendong Zhu¹

Affiliations

¹ BayRay Innovative Center, Shenzhen Bay Laboratory, Shenzhen 518032, China.
² State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Abstract

A late-stage functionalization (LSF) of the natural product andrographolide for the efficient assembly of a range of structurally interesting and diverse tricyclic-aza derivatives was developed. The key to the diversification is a photo-catalyzed intramolecular hydroamination reaction, and acridinium derivatives were demonstrated to be the optimal catalysts. Additionally, the synthesized tricyclic aza-andrographolide derivatives were found to inhibit human coronavirus with high potency.