Synthesis of a series of validoxylamine A esters and their biological activities

The worldwide reduction in food production due to pests and diseases is still an important challenge facing today. Validoxylamine A (VAA) is a natural polyhydroxyl compound derived from validamycin, acting as an efficient trehalase inhibitor with insecticidal and antifungal activities. To extend the application and discover green pesticide, a series of ester derivatives were prepared based on VAA as a lead compound. Their biological activities were investigated against three typically agricultural disease, Rhizoctonia solani, Sclerotinia sclerotiorum and Aphis craccivora.

This study involved 30 novel validoxylamine A fatty acid esters (VAFAEs) synthesized by Novozym 435 and they were characterized with high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and proton nuclear magnetic resonance (¹ H-NMR). Of these 30 derivatives, most compounds showed improved antifungal activity, and 12 novel compounds showed improved insecticidal activity. When reacted with pentadecanoic acid, compound 14 showed the highest inhibitory activity against R. solani [median effective concentration (EC₅₀ ) 0.01 μmol L^-1 ], while the EC₅₀ value of VAA was 34.99 μmol L^-1 . Furthermore, 21 novel VAFAEs showed higher inhibitory activity against S. sclerotiorum. Validoxylamine A oleic acid ester, compound 21, exhibited the highest insecticidal activity against A. craccivora [median lethal concentration (LC₅₀ ) 39.63 μmol L^-1 ], while the LC₅₀ value of Pymetrozine was 50.45 μmol L^-1 , a commercialized pesticide against A. craccivora.

Combining our results, esterification of VAA by introducing different acyl donors was beneficial for the development of new eco-friendly drugs in the field of pesticides.