Submitted to: Synthesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/14/2002
Publication Date: 1/15/2003
Citation: BARTELT, R.J., WEISLEDER, D., MOMANY, F.A. TOTAL SYNTHESIS OF HIMACHALENE SESQUITERPENES OF APHTHONA AND PHYLLOTRETA FLEA BEETLES. SYNTHESIS. 2003. v. 1. p. 117-123.
Interpretive Summary: A series of six compounds was synthesized in the laboratory to support research on the pheromones of several species of flea beetles which belong to the genera, Aphthona and Phyllotreta. Aphthona species are imported biological control agents of leafy spurge, a serious weed pest on western range lands, while Phyllotreta cruciferae is a significant pest of canola and rapeseed. Pheromones (natural chemicals that insects emit, often to attract mates) could be of practical use in the monitoring and management of both the beneficial species and the pest. Recently, six compounds were identified at NCAUR which occur only in the male flea beetles, (and curiously, most of the compounds occurred in both of the genera). The compounds are believed to have a pheromonal function, but demonstrating this requires a large supply of the compounds for tests of attraction in the field. The purpose of the present project was to prepare enough of the compounds so that these important field experiments can be conducted. The target compounds belong to a class called sesquiterpenes, which are somewhat complicated to synthesize but which were still accessible with "standard" chemical reactions. The synthetic compounds matched the natural ones from the beetles in every way. The successful synthesis will allow scientists to carry pheromone research in these important beetles to higher levels. Furthermore, having a "recipe" for the compounds meets one crucial need for their eventual adoption into practical insect management programs.
Technical Abstract: A total synthesis is presented for himachalene-related norsesquiterpene ketone 1 (racemic), based on the Robinson annulation and other standard reactions. The route involved five steps from cycloheptanone. A favorable result was that the desired diastereomer of 1 was obtained preferentially (97:3) over the unwanted one. Molecular modeling (ab initio calculations) aided in confirming the assignment of relative stereochemistry of 1 and in rationalizing the observed ratio of diastereomers. Three related sesquiterpene hydrocarbons and two alcohols were subsequently produced from 1. The six compounds occur naturally in several flea beetle species and likely serve a pheromonal function.