Lardolure

Scheme 27 summarizes Yamamoto s synthesis of lardolure (16), the aggregation pheromone of the acarid mite, Lardoglyphus konoi [45]. The key-step was the transformation of acetal A to hemiacetal B. 

SCHEME 8. Apphcation of the iterative conjugate addition in the synthesis of (—)-Lardolure. Adapted with permission from Acc. Chem. Res., 40, 179-188 (2007). Copyright 2007 American Chemical Society... 

An alternative combination of an aggregation-alarm pheromone system is found in L. konoi. This species produces the aggregation pheromone lardolure (44) as a minor component, and the alarm pheromone neral (2) as a major component. If both pheromones are presented simultaneously, aggregation pheromone activity manifests only after the alarm pheromone has dissipated. Furthermore, it seems likely that the mites can regulate the production of each component independently, because the evidence suggests that each is produced at a different site. Therefore, lardolure may be produced essentially continuously, and its function as an attractant is temporarily overridden by the rapid release of the alarm pheromone under adverse circumstances. 

Kuwahara, Y., Matsumoto, K., Wada, Y. and Suzuki, T. (1991a). Chemical ecology on astigmatid mites. XXIX. Aggregation pheromone and kairomone activity of synthetic lardolure (1 3 5 7 H. 3,5,7 - leur a m c ill I decy 1 formate and its optical... 

This novel annelation not only provides a route to chiral lactones, but was applied to a synthesis of a diol (8) from the acetal 7 as a precursor to (- )-lardolure (9). 

Two useful hints were available about the stereochemistry of the natural 90. First, the absolute configuration at C-l of lardolure was assigned as R by the ORD (optical rotatory dispersion) comparison of the natural 90 with (SH-methylheptyl formate. Secondly, Y. Kuwahara observed that his synthetic mixture consisting of all the eight diastereomers of 90 gave seven peaks when analysed by capillary GC, and the peak showing the shortest retention time coincided with that of the natural 90. 

Figure 4.40 Elucidation of the relative configuration of lardolure by synthesis. Reprinted with permission of Shokabo Publishing Co., Ltd...

Figure 4.40 summarizes our synthesis of l,3-yy -( )-lardolure, l,3,5-yy -( )-lardolure and 5,7-syn-( )-lardolure.73 All of these three synthetic samples contained a component with the same GC retention time as that of the natural 90. The relative configuration of the natural 90 was therefore proposed as all-yyn. 

We then synthesized the two enantiomers 90 and 90 of lardolure as shown in Figure 4.41.74 The first task was the enantiomer separation (optical resolution) of ( )-lactone A, which was an intermediate in the synthesis of l,3,5-yy -( )-lardolure. Treatment of ( )-A with (3 )-prolinol furnished B, whose 3,5-dinitrobenzoates C and D could be separated by silica-gel chromatography. The absolute configuration of D could be determined as depicted by its conversion to the known lactone (-)-F via (—)-E. The... 

Our synthetic (l,R,3R,5R,7.R)-lardolure (90) showed the ORD curve identical to that of the natural pheromone,74 and attracted mites such as Lardoglyphus konoi, Carpoglyphus lactis, Aleuroglyphus ovatus and Tyrophagus putrescentiae. The enantiomer (1S,3S,5S,7S)-W inhibited the action of 90 on L. konoi, but neither attractive nor inhibitory against the action of 90 on C. lactis. 

Kuwahara, Y., Thi My Yen, L., Tominaga, Y., Matsumoto, K. and Wada, Y. (1982) 1, 3, 5, 7, Tetramethyldecyl formate, lardolure aggregation pheromone of the acarid mite, Lardoglyphus konoi (Sasa et Asanuma). Agricultural and Biological Chemistry 46, p. 2283. 

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