Chiral Synthesis of Pefurazoate Enantiomers and Their Antifungal Activity to Gibberella fujikuroi

Abstract

A new azole fungicide, pefurazoate (4-pentenyl (RS)-2-[(2-furylmethyl) (imidazol-1-ylcarbonyl) amino] butanoate, Healthied^®) has one Chiral carbon center in its structure. From optically active 2-aminobutanoic acid, we prepared two enantiomers of pefurazoate, (R)-isomer and (S)-isomer, whose optical rotations in methanol were [α]²⁰_D+10.7 and [α]²⁰_D-9.90, respectively, and studied their antifungal activity and ergosterol biosynthesis in Gibberella fujikuroi. The antifungal activity of the (S)-isomer was about 30 times higher than that of the (R)-isomer. At 0.24ppm, the in vitro inhibition of ergosterol biosynthesis by the (S)-isomer was four times higher than by the (R)-isomer. These results indicate that the (S)-isomer of pefurazoate is an active form fungicidal to G. fujikuroi.