Synthesis And Properties Of Novel Biologically Active Oxazolopyrimidone And Biscarbohydrazide Derivatives

Oxazolopyrimidine derivatives has become a focus of the research on pharmaceuticals for their uniqe pharmacological activity.The carboxyterminal processing protease of D1 protein(CtpA)is predicted to be an excellent target for the discovery of a general broad-spectrum herbicide,thus,the exploiture of this kind of herbicides is profound and promising.In this paper,we studied the synthesis of novel oxazolopyrimidine derivatives via aza-Wittig reaction.Furthermore,lead compounds selected by virtual screening approach were also synthesized and tested for fungicidal activities.The structure of these compounds were confirmed by IR,~1H NMR,MS, element quantitative analysis and X-ray diffraction.It may be summarized as follows:1.Under optimal conditions,the atmosphere of nitrogen and the proportion of approximately equimolecular starting materials,iminophosphorane 4 has been synthesized in good purity.2.Oxazolo[5,4-d]pyrimidin-7(6H)-one derivatives were synthesized by the reaction of carbodiimides with amines(primary amines and secondary amines)and phenol.The reaction conditions was studied and the results showed that the cyclization of carbodiimides 5 with amines should be in the presence of RONa under protection of nitrogen,the cyclization of carbodiimides 5 with phenol in the presence of solid potassium at room temperature to 40℃.3.Oxazolo[5,4-d]-1,2,4-triazolo[1,5-a]pyrimidin-9(3H)-one derivatives were synthe-sized via repeated aza-Wittig reaction,which boarded the utilization of aza-Wittig in organic synthesis.4.Using a virtual screening approach,we have discovered that Xanthene-9-carbohydrazide derivatives are CtpA inhibitors.Subsequent derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives.5.The biological activities of partial target compounds were studied.The results showed that several compounds 8 have good fungicidal activities against Botrytis cinereapers.At 100ppm,the fungicidal activity of compound 8e,8i and 8n against Botrytis cinereapers were 91%,83%and 95%,respectively.Other compounds 7 and 8 did not exhibit obvious inhibition of Rhizoctonia solani,Gibberella zeae,Botrytis cinereapers,Dothiorella gregaria,Fusarium oxysporium,Colletotrichum gossypii.The compounds 16 and 18 exhibited good herbicidal activity,at 100ppm,most compounds exhibited 90%-100%growth inhibition of Barnyard grass and Cole root and stalk, respectively.