Design and synthesis of novel coumarin analogs and their nematicidal activity against five phytonematodes

The presence of hydroxyl groups at the C4 and C7 positions in coumarin backbone has been proposed as a potential modification site for providing excellent bioactivity according to previous studies. A series of novel coumarin derivatives were rationally designed and synthesized by use of a complex catalytic system for a targeted modification at the above sites. These derivatives were assayed for nematicidal activity. As predicted, the derivatization enhanced the activity of the coumarins against five nematodes. Compounds 7b, 9a, 10c and 11c showed significant strong nematicidal broad spectrum activity against all tested nematodes. Compound 10c was the most effective with the lowest LC50 values against Meloidogyne incognita (5.1 μmol/L), Ditylenchus destructor (3.7 μmol/L), Bursaphelenchus mucronatus (6.4 μmol/L), Bursaphelenchus B. xylophilus (2.5 μmol/L) and Aphelenchoides besseyi (3.1 μmol/L), respectively. A brief investigation on the structure–activity relationships (SAR) revealed that the targeted modification by a C7 hydroxyl was optimum compared with that of a C4 hydroxyl and that the coupling chain length was crucial for the nematicidal activity.

A series of novel coumarin analogs were effectively synthesized by a targeted modification at C4 and C7 hydroxyl groups and their nematicidal activity was investigated to discover promising compounds. As predicted, the derivatization enhanced the activity of the coumarins against five phytonematodes. The investigation on the structure–activity relationships (SAR) has provided useful guidelines for the development of coumarin based nematicides.Figure optionsDownload as PowerPoint slide