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

Authors: MIN, LI-JING - Huzhou University; SHEN, ZHONG-HUA - Zhejiang University; Bajsa-Hirschel, Joanna; Cantrell, Charles; HAN, LIANG - Zhejiang University; HUA, XUE-WEN - Liaocheng University; LIU, XING-HAI - Zhejiang University; DUKE, STEPHEN - University Of Mississippi

Submitted to: Pesticide Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2022
Publication Date: 9/7/2022
Citation: Min, L., Shen, Z., Bajsa Hirschel, J.N., Cantrell, C.L., Han, L., Hua, X., Liu, X., Duke, S.O. 2022. Synthesis, crystal structure, herbicidal activity and mode of action of new cyclopropane-1,1-dicarboxylic acid analogues. Pesticide Biochemistry and Physiology. https://doi.org/10.1016/j.pestbp.2022.105228.
DOI: https://doi.org/10.1016/j.pestbp.2022.105228

Interpretive Summary: Herbicide resistant-weeds drastically impact crop yield causing billion dollar losses every year around the world. This problem makes weed management practices frequently insufficient and the issue needs urgently new solutions like development of herbicides neutralizing new plant targets. In this study, authors designed and synthesized a new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway unique for plants. Research on KARI inhibitors is especially important since there are no available commercial herbicides with such mode of action. The analogues displayed moderate inhibition of KARI activity and week herbicidal activity against lettuce and bentgrass. The discrepancy between in vivo and in vitro activity needs more extensive research in future.

Technical Abstract: 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 tested 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 molecular docking simulation with KARI results supportinged inhibition of KARI as their mode of action.