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.

设计并合成了一系列新的环丙烷-1,1-二羧酸 (CPD) 酸类似物。CPD 是酮醇酸还原异构酶 (KARI) 的抑制剂，KARI 是植物中支链氨基酸途径的一种酶。CPD 类似物的结构通过¹ H NMR 和 HRMS 表征。通过 X 射线衍射进一步阐明了N,N'-双(4-(叔丁基)苯基)环丙烷-1,1-二甲酰胺的结构。测试了这些化合物对生菜 ( Lactuca sativa ) 和翦股颖 ( Agrostis stolonifera ) 的除草活性。大多数这些化合物对这两种植物都表现出低除草活性。其中，N,N′-bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide 对翦股颖表现出中等活性。还通过实验和分子对接模拟评估了 CPD 类似物对 KARI 活性的抑制作用，结果支持抑制 KARI 作为它们的作用模式。这些结果为设计更有效的 KARI 抑制剂提供了基础。