Neonicotinoid Insecticide Usefulness for Crop Protection and Public Health

Neonicotinoid Insecticide Usefulness for Crop Protection and Public Health

The world wide efforts in the search for natural products and analogues for the crop protection market have been remarkably successful, foremost in the field of insect control. It is interesting to note, that in this indication higher plants contributed significantly to this success as sources for highly active agents.

Pyrethroids

The pyrethroids are a prime example how a biologically active natural product served as a template for the creation of economically and ecologically sound hygiene and crop protection insecticides by chemical synthesis. To adequately summarize this fascinating topic and to pay tribute to the enormous efforts put into synthesis and into studies of very complex structure-activity relationships, would by far exceed the size of a general review. Three recent reviews, excellently written by firsthand authors, cover this field in detail. In this summary the practical results which emerged from the research programs in academia and in industry are highlighted.

1 pyrethrin I R = CH32 pyrethrin II R = COOCH3

Powdered heads of the flowers of Tanacetum cinerariifolium (also known as Chrysanthemum c.or Pyrethrum c.) or an extract thereof have long been used and are still popular as household insecticides. Of the six insecticidal components of pyrethrum extract, 1 is mainly responsible for kill, whereas 2 exerts mainly knockdown activity. The insecticidal metabolites in pyrethrum are all unstable when exposed to light and air. Therefore, these natural products are not suited for agricultural application. The pioneering work by Staudinger and Ruzicka, carried out during 1910-16 , led to the correct structural assignment of the acid part of 1, (1R)-trans-chrysanthemic acid and of 2, (1R)-trans-pyrethric acid. The same authors also synthesized a number of analogues of the natural esters by varying both the acid and alcohol parts. They noticed, that both the acid and the alcohol part can be replaced by structural mimics with retention of some insecticidal activity , although none of the active analogues came close to the activity of the natural products. Nevertheless, this early work was a valuable source for future research which aimed at highly active, photostable pyrethroids. The topic was picked up at the US Department of Agriculture and at the Rothamstead Experimental Station in the UK. Then Sumitomo and Roussel-Uclaf joined in, while other companies followed later.The first effort concentrated on replacing (S)-pyrethrolon, the photolabile alcohol part of 1 and 2. Allethrin (3) which is structurally closely related to pyrethrin I (1), was the first synthetic pyrethroid to reach the market . Its most active isomer, S-bioallethrin (4), was later commercialized by Roussel-Uclaf. In Sumitomo's tetramethrin (5) the natural pyrethrolone is replaced by a much simpler isosteric substructure . A major achievement was the synthesis of resmethrin (6) and bioresmethrin (7) which had a distinctly higher insecticidal activity than the natural pyrethrins .

3 allethrin USDA

4 S-bioallethrin USDA, Roussel-Uclaf

5 tetramethrin Sumitomo

6 resmethrin Rothamstead

7 bioresmethrin Rothamstead

8 phenothrin Sumitomo

9 cyphenothrin Sumitomo

Despite their high activity, bioresmethrin (7) and also ...