Novel Fluorinated 7-Hydroxycoumarin Derivatives Containing an Oxime Ether Moiety: Design, Synthesis, Crystal Structure and Biological Evaluation

A series of fluorinated 7-hydroxycoumarin derivatives containing an oxime ether moiety have been designed, synthesized and evaluated for their antifungal activity. All the target compounds were determined by1H-NMR,13C-NMR, FTIR and HR-MS spectra. The single-crystal structures of compounds4e,4h,5hand6cwere further confirmed using X-ray diffraction. The antifungal activities againstBotrytis cinerea(B. cinerea),Alternariasolani(A. solani),Gibberella zeae(G. zeae),Rhizoctorzia solani(R. solani),Colletotrichum orbiculare(C. orbiculare) andAlternaria alternata(A. alternata) were evaluated in vitro. The preliminary bioassays showed that some of the designed compounds displayed the promising antifungal activities against the above tested fungi. Strikingly, the target compounds5fand6hexhibited outstanding antifungal activity againstB. cinereaat 100 μg/mL, with the corresponding inhibition rates reached 90.1 and 85.0%, which were better than the positive control Osthole (83.6%) and Azoxystrobin (46.5%). The compound5fwas identified as the promising fungicide candidate againstB. cinereawith the EC50values of 5.75 μg/mL, which was obviously better than Osthole (33.20 μg/mL) and Azoxystrobin (64.95 μg/mL). Meanwhile, the compound5fshowed remarkable antifungal activities againstR. solaniwith the EC50values of 28.96 μg/mL, which was better than Osthole (67.18 μg/mL) and equivalent to Azoxystrobin (21.34 μg/mL). The results provide a significant foundation for the search of novel fluorinated 7-hydroxycoumarin derivatives with good antifungal activity.Keywords:fluorinated 7-hydroxycoumarin;oxime ether derivatives;synthesis;crystal structure;antifungal activity