Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound demonstrating the most potent anti-TMV activity. At 500 μg/mL, compound achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides and . Notably, the -diastereomer (-) exhibited superior antiviral activity compared to the -diastereomer (-). Mechanistic studies revealed that - could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound , with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.