Synthesis and biological evaluation of burnettiene A derivatives enabling discovery of novel fungicide candidates.

An antifungal polyene-decalin polyketide natural product, burnettiene A () has been re-discovered from the culture broth of (current name: ) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated from . The antifungal activity of against has been reported. However, only one fungal species for the antifungal activity of has been revealed, and details of the antifungal activity against other pathogenic fungus remain unknown. After extensive screening for antifungal activity, we found that exhibits broad antifungal activity against pathogenic plant fungi, including , , , , and . Furthermore, we synthesized 12 derivatives from and evaluated their antifungal activity to reveal the detailed structure-activity relationship. The methyl ester derivative showed antifungal activity against 12geneΔ0HSR-iERG6 100-fold more potent than that of . Our research indicates that would be a promising natural product as a new fungicidal candidate and the methyl ester derivative especially has great potential.