Harnessing Natural Products by a Pharmacophore‐Oriented Semisynthesis Approach for the Discovery of Potential Anti‐SARS‐CoV‐2 Agents

Autor: Yuan‐Fei Zhou, Bing‐Chao Yan, Qian Yang, Xin‐Yan Long, Dan‐Qi Zhang, Rong‐Hua Luo, Han‐Yu Wang, Han‐Dong Sun, Xiao‐Song Xue, Yong‐Tang Zheng, Pema‐Tenzin Puno
Rok vydání: 2022
Předmět:
Zdroj: Angewandte Chemie. 134
ISSN: 1521-3757
0044-8249
DOI: 10.1002/ange.202201684
Popis: Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC
Databáze: OpenAIRE
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