Synthesis and Structure-Activity Relationship Studies of Nicot-lactone Analogues as Anti-TMV Agents
Hong-Wei He, Yuan Chi, Cai-Yun Chen, Fei-Yu Wang, Jia-Xin Wang, Dan Xu, Huan Zhou and Gong Xu
Synthesis-Stuttgart
https://doi.org/10.1055/a-1814-9637
Abstract
The synthesis of the originally proposed structure of (+/-)nicotlactone A, a potent antiviral lignan with three continuous chiral centers, is reported 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 enabled 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.