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Published on: February 24, 2015
Epimerization of Yahazunol-Related Meroterpenoids for Antifungal Leads
Shengxin Sun1, Shiqi Fu1, Nvdan Hu1
1State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
Abstract:
We herein disclose that the epimerization of yahazunol can lead to an antifungal enhancement. Yahazunol-related drimane meroterpenoids and pseudonatural mimics were synthesized based on an improved synthesis of 9-epi-borono-sclareolide and the concomitant Suzuki coupling. Several 9-epi-drimane meroterpenoids presented antifungal activity. The new stereoisomer 9-epi-yahazunol (EC50 = 4.32 μM) and its analog S-T5 (EC50 = 2.8 μM) showed much better antifungal activity than yahazunol (EC50 >150 μM) against Rhizoctonia solani. Compound S-T5 possesses a promising in vivo efficacy against R. solani, with preventive efficacies of 87% and 71% at 100 and 50 μM, respectively. It not only induced wizened and wrinkled mycelia but also caused cell membrane damage or disruption in R. solani, as evidenced by a series of biochemical investigations. The biosafety assessment showed that S-T5 had no adverse effects on seed germination. Configuration inversion may be an alternative strategy for developing new potent antifungal mimics of drimane meroterpenoids.
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