Synthesis, anti-oomycete and anti-fungal activities of novel cinchona alkaloid derivatives containing sulfonate moiety.

Using cinchona alkaloid as the lead compound, twenty-four cinchona alkaloid sulfonate derivatives (1a-l, 2a-c, 3a-c, 4a-c, and 5a-c) were designed and prepared by modifying their C9 position, and structurally confirmed by 1H NMR, 13C NMR, HRMS and melting points. Moreover, the stereochemical configurations of compounds 1f and 1l were unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we determined the anti-oomycete and anti-fungal activities of these target compounds against Phytophthora capsici and Fusarium graminearum in vitro. The results showed that two compounds 4b and 4c exhibited prominent anti-oomycete activity, and the median effective concentration (EC50) values of 4b and 4c against P. capsici were 22.55 and 16.32 mg/L, respectively. This study suggested that when the C9 position of cinchona alkaloid sulfonate derivatives is in the S configuration and the 6'-position methoxy group is not present, the anti-oomycete activity is superior. In addition, five compounds 1e, 1f, 1k, 3c and 4c displayed significant anti-fungal activity, with EC50 values of 43.64, 45.07, 80.18, 48.58 and 41.88 mg/L against F. graminearum, respectively. This result indicates that only when a specific substituent is introduced into the structural framework of the target compound, the corresponding compound exhibits significant inhibitory activity against fungi.