Pyrethrins, development from natural

As these compounds seem to lose the selective toxicity characterized by natural pyrethrins, we should learn from natural pyrethrins to develop safer pyrethroids. 

A newer class of insecticides is the pyrethroids. These are synthetic derivatives of pyrethrins, which are natural extracts from chrysanthemums. Pyrethroids have been developed to be more stable (and thus more effective as insecticides) than the pyrethrins, which are particularly instable in light. Pyrethroids are frequently used as broad-spectrum insecticides. They have high insect toxicity, but lower mammalian toxicity than their organophosphate or carbamate counterparts. Pyrethroids are still limited in effectiveness due to their environmental lability, their high cost, and their potential for resistance development. 

Pyrethrin is a natural insecticide obtained from the powdered flower heads of several species of Chrysanthemum. The active substances in pyrethrum, principally pyrethrins I and II, are contact poisons for insects and cold-blooded vertebrates. Although powders made from Chrysanthemum extracts have found widespread use, the active substances in them are destroyed rapidly in the environment. In an effort to develop synthetic compounds as effective as the natural insecticides but with greater biostability, chemists prepared a series of esters related in structure. Among the synthetic pyrethrenoids now in common use in household and agricultural products are permethrin and bifenthrin. 

The change in the alcohol moiety to allethrone led to the development of the first synthetic pyrethroid, allethrin. It also led to improved chemical stability of the natural pyrethrins and to reduced cost, because the original pyrethrins had been sourced from natural products (LaForge and Soloway 1947). The stability of alle-thrin made it superior to the natural pyrethrins in both kill and knock-down effects against mosquitoes. Allethrin s successful discovery was followed by the development of other successful pyrethroids, to wit, tetramethrin (Kato et al. 1965) (1965, patent appl date) from tetrahydrophtalimide, resmethrin (Elliott et al. 1967) (1967, patent appl date) from 5-benzyl-3-furylmethyl alcohol and phenothrin (Fujimoto et al. 1973) (1968, patent appl date) by changing a-benzylfuran to phenoxyphenyl. 

Pyrethrolone and cinerolone make up the keto alcohol moiety of the pyrethrins. Both of these keto alcohols have one asymmetric carbon at the 4-position and a double bond in the side chain which is capable of cis-trans isomerism in the 2-position. It is possible, therefore, to have four stereoisomers for each keto alcohol. Katsuda et al. (22) show that only the ( + ) form occurs in the natural esters. Elliott (8) has shown recently, by a new procedure developed to obtain pure ( + ) pyrethrolone, that the hitherto unidentified prye-throlone C is in reality pyrethrolone contaminated with thermally isomerized material. (+) Pyrethrolone forms a crystalline monohydrate from which the pure alcohol is obtained. The natural configurations of the keto alcohols in the esters are insecticidally more active, as is the case with the acid moiety. 

Currently pest control by natural plant extracts is practiced primarily by subsistence farmers in those less developed part of the world where it is still an economic necessity.(ref. 3). Of the approximately 2000 plant species with known insecticidal properties (ref. 4), few have been developed commercially. These include the pyrethrins, rotenones and some of the alkaloids. Pyrethrins were the most important natural plant extracts in the early commercial insecticide formulations and were already in use in Persia and Yugoslavia during the early 1800s. By 1939 pyrethrum imports to the United States were 13-5 million lbs, declining from this peak as the synthetic analogs (e.g., the allethrins) appeared on the market. The addition of stabilizers (antioxidants) and synergists to the original pyrethrum formulations saved the natural product from commercial extinction. Currently the demand for pyrethrum flowers is still over 25,000 tons per annum—met by hand-harvested crops from Ecuador, Kenya and Tanzania (ref. 5) ... 

Analysis of process development data - The following illustrates how PDU data can be used to develop a commercial SCFCO2 plant s process design. This data is provided by Marc Sims on pyrethrins, a natural insecticide extracted with subcritical and supercritical carbon dioxide from pyrethrum flowers (a species of chrysanthemum). 

In the last century, the development of organophosphorus, carbamate, and organochloride insecticides was followed by synthetic pyrethroids. As a result, pyrethroids are now used frequently in the domestic milieu. Pyrethroid insecticides are synthetically derived from the molecular structure or sharing the same mechanism of action of natural pyrethrins that have broader spectmm of activity, more stability, and residual activity (persists longer than that of natural pyrethrins) and include the following allethrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, flumethrin, fluvalinate, tau-fluvalinate, and permethrin (see structure in Fig. 137.2). They are lipophilic compounds and generally of low acute oral toxicity to mammals but are very toxic to aquatic organisms. When synthetic pyrethroids are administered to mammals parenterally, the synthetic pyrethroids are neurotoxic. 

Synthetic pyrethroids have been developed to improve the specificity and activity of the natural insecticide pyrethrin, which are present in pyrethrum, an extract from the flowers of Chrysanthemum cinerarifolium. Pyreihroid pesticides have achieved remarkable effectiveness and set new standards for contact insecticides through improvements made during decades of research. Therefore, several structural modifications have been introduced over time in order to inaease photostability, air stability and insecticidal activity (Sogorb and Vilanova 2(X)2). 

The development of the pyrethroids from the pyrethrins serves as an example of the most successful development of a commercially important synthetic insecticide from a natural precursor. The commercial pyrethroids are among the most active insecticides known and they control a wider range of insect and acarid pests at lower application rates than most other insecticides. Their high toxicity to insects and low mammalian toxicity make these compounds a role model for all present and future insecticides. 

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