Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus.

Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5I, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure-activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a-9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.