Study On Synthesis And Bioactivity Of Acylated Validoxylamine A Derivatives

Validoxylamine A, the aglycone of jinggangmycin A, is a trehalase inhibitor with strong inhibitory activity against trehalases in all creature bodies examined. In this paper, three kinds of acylated validoxylamine A derivatives were reported and the bioactivities of them were determined. Thus, the thesis included the following aspects:(1) Validoxylamine A (1-3) was prepared by hydrolysis of jinggangm-ycin A (1-2) in the presence of sulfuric acid with 69.0% yield, and it was further purified by ion exchange method. The structure of the obtained 1-3 was confirmed by IR, MS, ¹H NMR, ¹³C NMR and ¹H-¹H COSY spectra.(2)Six new 7,7'-di-O-(O, O-disubstitutedthiophosphoryl)-validoxylam-ine A derivatives (3-1～3-6) were synthesized by acylating validoxylamine A with O, O-disubstituted thiophosphoryl chloride in yields of 42.0-52.8%.(3) Ten new 7,7'-O,O-diacylvalidoxylamine A derivatives (4-1～4-10) were synthesized by acylating validoxylamine A with acyl chloride or mono-carboxylic acids in yields of 45.6～62.4%; and five new 4,7:4,7'-di-O-biacylvalidoxylamine A derivatives (4-11～4-15) were synthesized by acylating validoxylamine A with biacyl chloride in yields of 21.7～35.2%.(4)Two isopropylidene validoxylamine A derivatives (5-1 and 5-2) were synthesized by treatment of validoxylamine A with 2,2-dimethoxyl- propane in yields of 35.2% and 27.1% respectively; Compound 5-3 was synthesized by the reaction of 5-2 with triphosgene and dimethylamine in one pot with 46.5% yield; Deprotected of 5-3 afforded compound 5-4 in 51.1% yield. Structures of all compounds were confirmed by IR, MS, ¹H NMR and ¹³C NMR spectra.(5) The bioassay showed that all of 7,7'-di-O-(O,O-disubstitutedth- iophosphoryl)-validoxylamine A derivatives displayed insecticidal activities; Some of acylvalidoxylamine A derivatives exhibited high insecticidal and fungicidal activities. When the concentration of compounds 3-2, 3-3 was at 500 mg/L, the mortality of Aphis meolicaginis and Leucania seoarata reached 100%; and the mortality of Aphis meolicaginis reached 100% at the same concentration of compounds 4-10, 4-11.