Synthesis and fungicidal activity study of novel daphneolone analogs with 2,6-dimethylmorpholine

A series of novel daphneolone analogswas designed and synthesized on the basis of natural product 1, 5-diphenyl-2-penten-1-one (I) from Stellera chamaejasme L. as lead compound, whereby 2, 6-dimethylmorpholine moiety was introduced to replace 1-phenyl group. Their structures were confirmed by IR, ¹H NMR, and HRMS (ESI) or elemental analysis, ¹³C NMR for some representative compounds. The two isomers of target compounds were separated and identified by NOESY technique and chemical method. All of the synthesized compounds have been evaluated for anti-plant pathogenic fungi activities. The results showed that some compounds exhibited moderate to good antifungal activities against tested fungi at the concentration of 50 mg/L. Among them, compound 7d, with a 4-bromine-substituted phenyl group and cis-2, 6-dimethylmorpholine moiety, displayed best activity with an EC₅₀ of 23.87 μmol/L against Valsa mali, superior to lead compound I. In addition, preliminary structure-activity relationship analysis indicated that, between two isomers of target compounds, the antifungal activities of the isomer with cis-2, 6-dimethylmorpholine were better than the trans-isomer.