Design, Enantioselective Synthesis, and Antiviral Activities against Tobacco Mosaic Virus (TMV) of Axially Chiral Biaryl Derivatives

A series of novel biaryl ester derivatives were synthesized using N-heterocyclic carbene (NHC) catalysis, and their efficacy against Tobacco Mosaic Virus (TMV) was assessed. Biological assays showed that some derivatives displayed significant antiviral properties, with compound (rac)-3l exhibiting the most potent in vivo antiviral protective activity against TMV (EC50 = 105.8 μg/mL), outperforming the commercially available antiviral agent ningnanmycin (EC50 = 138.8 μg/mL). Significantly, the (R)-3l isomer demonstrated markedly enhanced antiviral activity compared to its (S)-3l counterpart, with the difference reaching statistical significance (p R)-3l enhanced the activity of defense enzymes and increased the levels of proteins associated with photosynthesis and the tricarboxylic acid cycle, contributing to the mitigation of viral infection. This study offers valuable insights into the role of axially chiral compounds in protecting plants from viral infections.