Design,Synthesis And Antifungal Activity Of Novel 3,4-Dihydroisoquinolinium Derivatives

Plant pathogenic fungi are one of the main factors leading to plant diseases,which not only lead to decrease of the quality and quantity of agricultural products but also seriously threaten the health of humans and animals.For a long time,chemical pesticides have been the key means to control phytopathogenic fungi and have achieved significant control effects.However,the long-term use of pesticides has also led to serious drug resistance and environmental problems.Therefore,it urgently need to develop high-efficiency,low-toxicity,and environmentally friendly plant-derived pesticides.Isoquinoline alkaloids are widely distributed in nature.They are a kind of natural ingredients with diverse physiological activities and extensive medicinal value.They also extent many activities in agriculture,such as antifungal,insecticidal and acaricidal,and have important development and application potential.Taking natural active molecules as the research basis,follow on using chemical methods to modify the structure,have become the main method for the development of natural products.In this paper,two kinds of 42 novel 3,4-dihydroisoquinolinium derivatives were designed and synthesized base on sanguinarine and molecular splicing strategy.Their antibacterial activities were determined by the growth rate method.Preliminary activities showed that most of the target compounds have moderate antibacterial activity.Compounds a-17（96.9%）,and b-14（89.7%）showed better antibacterial activity than template compound sanguinarine（79.8%）.The structure-activity relationship showed that the antibacterial activity of diphenyl ether（group a）was better than benzoic acid（group b）for isoquinoline segments with different 2-positions;For class a,CN and CF₃increase activity,while CH₃and COOCH₃decrease activity;For class,b,7-halogenation of isoquinoline mother nucleus decreases activity.This thesis bases on the principle of pharmacophore splicing to construct two series of novel 3,4-dihydroisoquinolinium derivatives and initially reveals the structure-activity relationship of them.The design and synthesis of the title compounds provide a certain experimental basis for structural optimization of isoquinoline alkaloids.