Synthesis, anti-oomycete and anti-fungal activities of novel cinchona alkaloid derivatives bearing carbamate moiety

Abstract

In order to explore novel natural product-based anti-oomycete and anti-fungal agents, twenty cinchona alkaloid carbamate derivatives (1a-d, 2a-d, 3a-d, 4a-d, and 5a-d) were designed and prepared, and structurally confirmed by 1H NMR, 13C NMR, HRMS, and melting point. The stereochemical configuration of compound 1a was unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we evaluated the anti-oomycete and anti-fungal activities of these target compounds against Phytophthora capsici and Fusarium graminearum in vitro. The results showed that five compounds 1d, 2d, 3d, 4d, and 5d exhibited prominent anti-oomycete and anti-fungal activities, and the median effective concentration (EC50) values of 1d, 2d, 3d, 4d, and 5d against P. capsici and F. graminearum were 21.1, 16.6, 22.4, 14.4, 13.9 mg/L and 38.2, 19.8, 36.6, 30.3, 27.7 mg/L, respectively. This study suggested that when a specific substituent is introduced into the cinchona alkaloid skeleton, i.e. R1/R2 = Ph/Ph, the corresponding derivatives exhibit significant anti-oomycete and anti-fungal activities. And the configuration of the C8/9 position of the target compound is crucial for its anti-oomycete and anti-fungal activities, and 9S-configuration is optimal.