Design, Synthesis and Antifungal Activity of Novel Spiro-tetrahydroquinoline Derivatives

In an effort to develop novel fungicides, a series of spiro-tetrahydroquinoline derivatives containing a barbituric acid moiety was designed and synthesized based on the natural products tetrahydroquinoline alkaloids and hydrogenated indolizines. The chemical structures were confirmed by nuclear magnetic resonance(1H NMR and 13C NMR). In vitro antifungal activity showed that at 50 mg/L, all the targets showed moderate inhibition. Especially, compound Ik exhibited more than 51.0% inhibition on all the tested fungi. The inhibition rates of compound Il against Helminthosporium maydis and Colletotrichum lagenarium were 78.1% and 77.8%, respectively, which were as high as chlorothalonil. The preliminary structure-activity relationships showed that the spiro-tetrahydroquinoline skeleton had potential antifungal activity, and the introducing of pyrazole pharmacophore could enhance the antifungal effective and expand the antifungal spectrum. Thus, the findings of this study will contribute to the design of novel spiro-tetrahydroquinoline derivatives as antifungal agents to control phytopathogenic fungi in agriculture.