Pyrethrin I

Abstract: Natural pyrethrins, also called "pyrethrum" or "'pyrethrum extract", have long been known as insecticides. They are extracted from the flowers of Chrysanthemum cinerariaefolium Vis which contain six insecticidally active components, of which pyrethrin I and pyrethrin II are the most active (Head 1973, Elliott & Janes, 1973). Pyrethrins are widely used for domestic purposes and for the protection of stored food, but for general pest control in agriculture they are applied on a limited scale only. The total world production does not exceed about 350 tons per yr: cf. organophosphates, about 100,000 tons (Glynne-Jones, 1973: Fest & Schmidt. 1973). Their Limited use is due in part to economic reasons. Other factors restricting their use are their low photostability and high (bio) degradability, and pyrethrins are usually applied in combination with metabolic synergists. Apart from these problems, the pyrethrins possess excellent insecticidal properties combined with remarkably low mammalian toxicity. Their insect (topical) to mammalian (oral) toxicity ratio is much better than for the majority of other organic insecticides (Elliott, 1977). In mammals and other animals pyrethrins are rapidly metabolized and practically no residues are left in the biosphere. These favourable properties have stimulated the search for synthetic insecticides based on the structure of the pyrethrins. The production of synthetic pyrethroids on a commercial basis started with allethrin and cyclethrin around 1950 (O'Brien, 1967). These early compounds, however, still lacked sufficient stability and they are less effective against many species of insects than the natural product. At the moment the total yearly production of allethrin is some 100 tons. In the last decennium great progress has been made, notably by Ellion and co-workers, in the development of more stable and highly active pyrethroids and in the near future more widespread application of these compounds may be expected. Because of the complex molecular structure, the most important features of the pyrethroid molecule will be described briefly before the mode of action is discussed. Excellent reviews on the structural requirements of insecticidal active pyrethroids can be found elsewhere (Elliott, 1971, 1976a, b, 1977; Elliott eI al., 1974a). Most of the information presented in the next section is derived from these reviews. GENERAL FEATURES OF THE PVRETHROID MOI.ECLI,I."

Abstract: THE natural pyrethrins1–3, of which the most important constituent is pyrethrin I (1), are very active against a wide range of insect species, do not leave persistent residues, and have a long record of safe use; despite surprisingly high intravenous toxicity, they have low oral toxicity to mammals4. The related synthetic compound, bioresmethrin (2)5,6, has greater insecticidal activity (for example, about fifty times that of pyrethrin I, by topical application5, to a normal strain of houseflies), yet is even less toxic to mammals, both orally and intravenously4,7. Pyrethrin I and bioresmethrin are esters of (+)-trans [1R,3R]-chrysan-themic acid. We have now found that a simple modification of the acid side chain in bioresmethrin by which the four carbon atoms in the isobutenyl group are redisposed to a but-1-enyl substituent (as in 7) produces still greater insecticidal activity (about 100 times that of pyrethrin I to houseflies) whilst retaining low mammalian toxicity. Other changes of the acid side chain in bioresmethrin increase insecticidal activity further; for example the compound (10) with a cis-(Z)-butadienyl group and the dichlorovinyl compound (12) are both 2–3 times as potent as bioresmethrin.