Synthetic Studies of Salicylaldehyde-type Phytotoxins Isolated from Rice Blast Fungus

Abstract

The rice blast fungus Pyricularia oryzae is a causative agent of rice blast decease. P. oryzae produces several salicylaldehyde-type phytotoxins depending on the fermentation method: i.e., pyriculol (1), dihydropyriculol (2) and pyriculone (5) from shaking cultures; and pyriculariol (8) and dihydropyriculariol (9) from aeration and agitation cultures in a soy sauce-sucrose medium. Chemical studies of these phytotoxins including total synthesis, structure-elucidation, biosynthesis and structure-activity relationships are described. The absolute configuration of pyriculol (1) and epipyriculol (3) were established by the total synthesis of possible diastereomers. (R)-Pyricuol (7) has a nature-identical configuration as demonstrated by preparation of both enantiomers from (R)- and (S)-lactate respectively, via [2,3]-Wittig rearrangement and Stille coupling reactions. In contrast, natural pyriculariol (8) and dihydropyriculariol (9) are produced as racemates by the chiral synthesis from l-rhamnose (35) using a protective groups-free Stille coupling reaction under microwave irradiation. Biotransformation of the deuterio-labeled compounds indicated triene-aldehyde 33 as a putative key biosynthetic intermediates of the phytotoxins. Foliar application of the compounds on rice leaves revealed that both a salicylaldehyde and a side chain residues are important for the necrotic activity. In conclusion, the blast fungus P. oryzae produced optically active phytotoxins 1 and 2, as well as racemic phytotoxins 8 and 9, depending on the culture conditions. This research provides an interesting example of CH2OH and CHO groups interconversion occurring at the later stage of phytotoxin biosynthesis.