Synthesis and Structure–Activity Relationship Studies of Nicot­lactone Analogues as Anti-TMV Agents

Abstract

The synthesis of the originally proposed structure of (±)-nicotlactone A, a potent antiviral lignan with three continuous chiral centers, is reported here in 5 steps from methyl acrylate. The key steps of the synthesis included an In-catalyzed regioselective allylation and a Mn-catalyzed Mukaiyama hydration reaction. Our synthetic strategy also enables us to get the other three epimers and investigate the structure-activity relationship. The NMR data of the synthesized compounds do not match that of the isolated sample, indicating that the structure of nicotlactone A remains to be reassigned. All the synthetic target compounds were evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. Bioassay results indicated that (±)-8-demethylnicotlactone A displayed similar anti-TMV activity to the commercial agent ningnanmycin, thus being a promising candidate or lead compound for developing novel antiviral agents in crop protection.

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

“…28−30 Notably, nicotlactone A and its analogues, which contain a γ-butyrolactone moiety, have demonstrated significant antiviral properties in our previous studies. 29 Given the promising antiviral effects of γ-butyrolactones, this study focuses on the efficient synthesis of a series of γ-butyrolactone derivatives through the structural simplification of podophyllotoxin and its related biosynthetic intermediates (Figure 2b). The antiviral activities of these derivatives against TMV were systematically assessed, and the preliminary antiviral mechanism of action of the most potent compound was further investigated through transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and molecular docking analysis.…”

Furofuran Lignans for Plant Protection: Discovery of Sesamolin and Its Derivatives as Novel Anti-Tobacco Mosaic Virus and Antibacterial Agents

“…In recent years, large amounts of effective antiviral agents have been discovered through modification of natural products, such as dufulin, NK-007, methiadinil, 3-acetonyl-3-hydroxyoxindole (AHO), and xiangcaoliusuobingmi . In addition, many other natural product derivatives, including alkaloids, coumarins, , lignans, lactones, − sesquiterpenes, and polyphenolic compounds, , have also been reported to have good antiviral activities.…”