Synthesis, fungicidal activity and SAR of new amino acid derivatives containing substituted 1-(phenylthio)propan-2-amine moiety

Abstract

Fifteen novel amino acid derivatives were designed and synthesized using natural amino acid L-valine and two non-natural amino acids as raw materials. Fungicidal activities of these amino acid derivatives were tested against Phytophthora capsici. Most of these compounds possessed excellent activity against Phytophthora capsici at 50 μg/mL. Interestingly, compound isopropyl ((2S)-1-((1-((4-fluorophenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5c (EC₅₀=0.43 μg/mL), isopropyl ((2S)-1-((1-((3,4-dimethoxyphenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5g (EC₅₀=0.49 μg/mL), isopropyl ((2S)-1-((1-((4-(ethynyloxy)phenyl)thio)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 5h (EC₅₀=0.15 μg/mL) and isopropyl ((2S,3S)-1-((1-((4-(ethynyloxy)phenyl)thio)propan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)carbamate 5o (EC₅₀=0.31 μg/mL) exhibited remarkably high activities against Phytophthora capsici, which is better than that of positive control. It is possible that these amino acid derivatives, which possess excellent activity against Phytophthora capsici, may become novel lead compounds for the development of fungicides with further structure modification.

Graphical Abstract

Keywords:

• Amino acid
• synthesis
• substituted 1-(phenylthio) propan-2-amine
• fungicidal activity

Additional information

Funding

This work was supported financially by the National Key Research and Development Program of China (No. 2017YFD0200506) and Zhejiang Provincial Natural Science Foundation of China (No. LY19C140002, LY19B020009), the Chemical Company for Research (KYY-HX-20210140, KYY-HX-20190720).