Aim and Objective: 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
Materials and Methods: 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
Results: 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.
Conclusion: The drimane-amide derivatives A2 and A3 were the most promising derivatives
and should be selected as new templates for the potential antifungal agents.