Synthesis and Antifungal Activities of Drimane-Amide Derivatives from Sclareol

Plant diseases are caused by fungal pathogens lead to severe economic losses in many agriculture crops. And the increasing resistance of many fungi to commonly used antifungal agents necessitates the discovery and development of new fungicides. So this study was focused on synthesizing novel skeleton compounds to effectively control plant diseases.

A series of drimane-amide derivatives were designed, synthesized by aminolysis reaction of amine with intermediate sclareolide which was prepared from sclareol. The structures of all the synthesized compounds were confirmed using 1H NMR, 13C NMR, and HRMS (ESI) spectroscopic data. Their in vitro antifungal activity were preliminarily evaluated by using the mycelium growth rate method against five phytopathogenic fungi: Botrytis cinerea, Glomerella cingulata, Alternaria alternate, Alternaria brassicae, and Fusarium graminearum.

23 target compounds were successfully obtained in yields of 52-95%. Compounds A2 and A3 displayed favorable inhibitory potency against B. cinerea, G. cingulata and A. brassicae with IC50 values ranging from 3.18 to 10.48 µg/mL. These two compounds displayed higher fungicidal activity than sclareol against all the tested phytopathogenic fungi, and were more effective than the positive control thiabendazole against A. alternate and A. brassicae. The structure-activity relationship studies of compounds A1-10 indicated that both the position and type of substituent on the phenyl ring had significant effects on antifungal activity.

The drimane-amide derivatives A2 and A3 were the most promising derivatives and should be selected as new templates for the potential antifungal agents.