Synthesis, Bioevaluation and Structure-Activity Relationships of Novel N-Aryl Carbamate Derivatives as Potential Fungicidal Agents

The exploitation of natural products as lead compounds continues to serve as a vital strategy for the discovery of novel fungicidal agents. This work designed and synthesized a series of carbamate derivatives based on the natural product physostigmine and commercial carbamate fungicides. The title compounds were synthesized from readily available aromatic aldehydes via green Curtius rearrangement. The antifungal activities of those compounds were evaluated in vitro against eight phytopathogenic fungi. Many of the carbamate compounds exhibited good fungicidal activities. Among those molecules, compounds 3a9, 3b1, 3b2 and 3b12 outperformed the potency of the positive control azoxystrobin against certain fungi. Moreover, compounds 3b2, 3b3, and 3b12 showed outstanding and broad-spectrum in vitro antifungal activities against seven fungi with an inhibition rate of over 70% at 50 μg/mL. The preliminary structure-activity relationship (SAR) investigations demonstrated that N-aryl carbamates bearing a chlorine atom(s) or two bromine atoms on the di-substituted phenyl ring showed superior antifungal potency. This work might lay the foundation for investigating natural-source-based green fungicides, which exhibited great potential as novel antifungal lead compounds.