Synthesis And Antifungal Activities Of Pimprinine Derivatives

The use of environmentally compatible natural products as lead compounds to develop new pesticides is an effective way to achieve pesticide greening.The Pimprinine natural products are a class of alkaloids with a 5-(3’-indolyl)oxazole skeleton,widely distributed in various microbial metabolites.It has rich biological and physiological activities,such as antifungal,antioxidant,and anticancer,Anti-TB and so on.So it has broad research prospects to develop new,highly effective,low residue,and environmentally friendly chemical pesticides by screening out lead compounds from Pimprinine derivatives.Based on the principle of bioisosterism and active substructure splicing,Pimprinine was used as the lead compound,combined with the structural advantages of Streptochlorin,two series of 47 Pimprinine derivatives were designed and synthesized in this paper,including Series A:indoles are used as raw materials,36 compounds of 5-(3’-indolyl)imidazole derivatives were synthesized through Vilsmeier-Haack reaction and Van Leusen imidazole synthesis method;Series B:substituted indoles are used as raw materials,eleven 2-methyl-5-(substituted 3-indolyl)oxazole oxazole derivatives were synthesized by Friedel-Crafts reaction,Kornblum oxidative cyclization,and α-amino acid ring closure reaction.All target compounds were characterized by 1H NMR,13C NMR,HRMS.In addition,the absolute configurations of compounds A-4 and A-8 were determined by X-ray diffraction crystallography.Pimprinine derivatives were evaluated in vitro antifungal activities against Botrytis cinrea,Rhizoctonia solani,Alternaria solani,Gibberella zeae,Colletotrichum lagenarium and Alternaria Leaf spot.The data of primary antifungal activity screening shows:(1)Among the Pimprinine derivatives with oxazole replaced by imidazole fragments,although some compounds show a certain biological activity,such as A-9,A-10,A-11,A-20,A-31,A-32,fewer samples with good biological activity that can be tested in the next stage.(2)In compounds with various substituents introduced on the indolebenzene,the biological activity is generally good.For example,B-3,B-4,B-5,B-11,especially compound B-4,exhibited an inhibition rate of more than 85%for Botrytis cinrea and Colletotrichum lagenarium.It is hoped that the preliminary structure-activity relationship derived from this series will be used for further research,and through which higher activity fungicide molecules will be obtained.