Synthesis, crystal structure, herbicidal activity and mode of action of new cyclopropane-1,1-dicarboxylic acid analogues

• Published in: Pesticide biochemistry and physiology 2022-11, Vol.188, p.105228, Article 105228
• Main Authors: Min, Li-Jing, Shen, Zhong-Hua, Bajsa-Hirschel, Joanna, Cantrell, Charles L., Han, Liang, Hua, Xue-Wen, Liu, Xing-Hai, Duke, Stephen O.
• Format: Article
• Language: English
• Subjects: Cyclopropane-1,1-dicarboxylic acid analogues; Herbicidal activity; KARI; Mode of action; Molecular docking; Synthesis
• ISSN: 0048-3575; 1095-9939
• DOI: 10.1016/j.pestbp.2022.105228

A new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway in plants. The structures of CPD analogues were characterized by 1H NMR and HRMS. The structure of N,N′-bis(4-(tert-butyl)phenyl)cyclopropane-1,1-dicarboxamide was further elucidated by X-ray diffraction. The herbicidal activities of these compounds were tested against lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). Most of these compounds exhibited low herbicidal activity against both plant species. Among them, N,N′-bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide displayed moderate activity against bentgrass. Inhibition of KARI activity by the CPD analogues was also assessed experimentally and by molecular docking simulation with results supporting inhibition of KARI as their mode of action. These results provide the basis for design of more effective KARI inhibitors. A series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI). Their structures were confirmed by NMR, HRMS and X-ray diffraction. The KARI activity and herbicidal activity results indicated that some of them exhibited good activity. The mode of action was studied by using molecular docking. The SAR was also studied. [Display omitted] •The new cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized.•The herbicidal and KARI activity were examined with new CPD analogues and structure-activity relationship was studied.•The molecular property, molecular docking and ADMET prediction were done.