Sex Pheromone of the Azalea Mealybug: Absolute Configuration and Kairomonal Activity

The sex pheromone of the azalea mealybug, Crisicoccus azaleae (Tinsley, 1898) (Hemiptera: Pseudococcidae), includes esters of a methyl-branched medium-chain fatty acid, ethyl and isopropyl (E)-7-methyl-4-nonenoate. These compounds are exceptional among mealybug pheromones, which are commonly monoterpenes. Determination of the absolute configuration is challenging, because both chromatographic and spectrometric separations of stereoisomers of fatty acids with a methyl group distant from the carboxyl group are difficult. To solve this problem, we synthesized the enantiomers via the Johnson-Claisen rearrangement to build (E)-4-alkenoic acid by using (R)- and (S)-3-methylpentanal as chiral blocks, which were readily available from the amino acids L-(+)-alloisoleucine and L-(+)-isoleucine, respectively. Each pure enantiomer, as well as the natural pheromone, was subsequently derivatized with a highly potent chiral labeling reagent used in the Ohrui-Akasaka method. Through NMR spectral comparisons of these derivatives, the absolute configuration of the natural pheromone was determined to be S. Field-trap bioassays showed that male mealybugs were attracted more to (S)-enantiomers and preferred the natural stereochemistry. Moreover, the synthetic pheromones attracted Anagyrus wasps, indicating that the azalea mealybug pheromone has kairomonal activity.