Synthesis, Anti-Oomycete and Anti-Fungal Activities of Anhydride Derivatives of Oleanolic Acid.

Oleanolic acid is a pentacyclic triterpenoid extracted and isolated from the fruit of plants in the Ligustrum lucidum Ait. in the family Oleaceae. To discover biorational natural product-based pesticides, a series of oleanolic acid derivatives containing anhydride active skeletons were prepared by ingeniously introducing an active acyloxy group at its C-28 carboxyl position, and their structures were well characterized by 1H NMR, 13C NMR, HRMS, and m.p.. The stereochemical configuration of compound 8e was confirmed using single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete and anti-fungal agents against two serious agricultural pests, Phytophthora capsici and Fusarium graminearum we assessed. Amongst evaluated compounds, 1) Compounds 8h and 8j displayed significant anti-oomycete against P. capsici, with EC50 values of 54.73 and 65.15 mg/L, respectively. 2) The target compounds have obvious selectivity, and their anti-oomycete activity is significantly better than their anti-fungal activity. 3) Interestingly, there are significant differences in the structure-activity relationship of different substituents or the same substituent at different positions anti-oomycete and anti-fungal against P. capsici and F. graminearum, respectively. The study provides an idea for further exploring the bioactivities of 28-acyloxyoleanolic acid derivatives, and develops the application of 28-acyloxyoleanolic acid derivatives containing anhydride in agriculture.

Design, synthesis and anti-oomycete activity of 2-acyloxyhinokitiol derivatives.

In order to explore novel natural product-based anti-oomycete agent, ten 2-acyloxyhinokitiol derivatives (5a-j) were designed and synthesised, and structurally confirmed by 1H NMR,13C NMR, HRMS, and melting point. The stereochemical configuration of compound 5f was unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we evaluated the target compounds 5a-j as anti-oomycete activity against a serious agricultural disease of Phytophthora capsici. Among the ten hinokitiol ester derivatives tested, four compounds 5d, 5g, 5h and 5j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 23.59 mg/L), and the EC50 values of 18.90, 20.62, 13.61 and 21.29 mg/L, respectively. Especially compound 5h exhibited the best anti-oomycete activity against P. capsici with EC50 value of 13.61 mg/L. Overall, the anti-oomycete activities of 2-acyloxyhinokitiol derivatives is higher than that of 2-sulfonyloxyhinokitiol derivatives. The results laid a good foundation for the subsequent synthesis of hinokitiol ester derivatives with significant anti-oomycete activity.