Enantioselective antifungal activity of pefurazoate against pathogens of rice seed diseases

Pefurazoate is a 14 alpha -demethylation inhibitor of 24-methylenedihydrolanosterol (24-MDL) and has an asymmetric carbon atom in its structure. We previously reported that the antifungal activity of the (S)-(-)-isomer of pefurazoate against Gibberella fujikuroi was about thirty times that of the (R)-(+)isomer. This enantioselective antifungal activity was presumed to be due to an asymmetric molecular shape caused by the binding of a bulky 2-furanylmethyl group to a nitrogen atom adjacent to the asymmetric carbon atom. Therefore, to further elucidate the difference in antifungal activity between the two enantiomers of pefurazoate, we synthesized optically active N-methyl analogues of pefurazoate, and evaluated their antifungal activity. Optical (R)-(+)- and (S)-(-)-isomers of pefurazoate exhibited different activities against Cochliobolus miyabeanus and Pyricularia oryzae as well as Gibberella fujikuroi, but the N-methyl (R)-(+)- and (S)-(-)-isomers of the pefurazoate analogues had almost the same degree of activity against these three fungi and of inhibition of ergosterol biosynthesis in G. fujikuroi. These findings strongly suggest that the enantioselective antifungal activity of pefurazoate is due to its asymmetric molecular shape caused by substitution of the furan ring.