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

ABSTRACT: 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

SUBMITTER: Zhou YF 

PROVIDER: S-EPMC9074085 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature