Study On Derivation And Bioactivity Of Validoxylamine A And Hexahydropyridazine

This research focused on the chemical modification of natural compound validoxylamine A and small-molecular compound hexahydropyridazine.A series of new compounds were prepared,and their bioactivities were studied.Validamycins are safe and highly effective bio-pesticides with special modes of action.Validoxylamine A is the aglycone of the validamycin A,which exhibits a very strong competitive inhibitory activity against trehalases.In this part some new compounds of validoxylamine A derivatives were prepared based on validoxylamine A as the leading compound.Firstly,validoxylamine A was prepared by hydrolysis of validamycin A through the improved method of synthesis.Calcium carbonate was used as the neutralizing agent and validoxylamine A was crystallized directly from the neutralized solution.Usually,in the process of recrystallization,gelatiniform solid was obtained instead of powdery solid.This problem was solved through ultrasonic radiation.Then 2,3,4,7,4',7',5',6'-tetra-O- isopropylidene validoxylamine A and 3,4,4',7',5',6'-tri-O- isopropylidene validoxylamine A were prepared by heating the mixture of validoxylamine A,2,2-dimethoxy propane and p-toluenesulfonic acid.Single crystal of 2,3,4,7,4',7',5',6'-tetra-O-isopropylidene validoxylamine A was cultivated and tested by x-ray diffraction.Then mono-,di-,tri-,tetra- acetate of validoxylamine A and 7, 7'-di- triphenylmethyl-hex-acetate of validoxylamine A were prepared by controlling amount ratio and temperature,and purified by column chromatography(eluant CHCl₃/MeOH/H₂O/HOAc system).Secondly,ten new aminoformyl hexahydropyridazine derivatives were prepared by reaction with seven isocyanates which were prepared by us in advance.Then we selected m-trifluoromethyl phenyl aminoformyl hexahydropyridazine which was proved to have bioactivity as leading compound.Based on this compound we prepared four new aminoformyl hexahydropyridazine acylated derivatives and two new aminoformyl hexahydropyridazine cyclization derivatives.All these new compounds' bioactivities were studied and some new compounds display good bioactivities.