Synthesis of Pyrethroic Acids from Natural Products and from Isomeric Compounds: Strategy and Practice

Pyrethroic acids are essential constituents of the pyrethroids, which are now some of the most powerful commercially available insecticides. A number of syntheses of pyrethroic acids have been published since the elucidation of the structure of chrysanthemic acid, one of the naturally occurring acids present as esters in Chrysanthemum cinerarefolium Vis. This paper reports some results of the stereoselective synthesis of the most biologically active enantiomers of pyrethroic acids obtained over the last five years in our laboratory. Two different approaches, which have been patented by two leading European companies in the agrochemical field, have been carried out simultaneously. The first uses the cheap chiral natural products mannitol and tartaric acid as starting materials and allows the rapid construction of the cyclopropane framework. The second takes advantage of the isomeric relationship between dimethyl dimedone, a readily available, non-chiral compound and chrysanthemic acid. Enantioselective isomerisation of dimethyl dimedone to (1R)-cis- and (1R)-trans-chrysanthemic acid has been achieved successfully using a lipase. These two approaches to the synthesis of chrysanthemic acid are compared with related approaches in the literature, which use other natural products or isomers of chrysanthemic acid as starting materials.