Structure specific insecticides

While chlordene (43) has only a weak insecticidal effect, the efficiency of chlordane (41), which contains two more chlorine atoms, is 300 times greater, indicating that the efficiency of insecticides of the cyclodiene type is highly structure-specific. Even slight modifications of the molecule greatly affect the efficiency. 

Chlorinated pesticides are a small but diverse group of artificially produced chemicals characterized by a cyclic structure and a variable number of chlorine atoms. Most members of the group are resistant to environmental degradation and relatively inert toward acids, bases, oxidation, reduction, and heat. The parent compounds often have a number of related analogs and isomers, which show significant variation in toxicity and persistence. In some instances, these isomers have been used to develop highly specific insecticides, such as y-hexachlorocyclohexane, which shows low toxicity to plants and mammals. 

Casida, J.E. and LJ. Lawrence. 1985. Structure-activity correlations for interactions of bicyclophosphorus esters and some polychlorocycloalkane and pyrethroid insecticides with the brain-specific t-butylcyclo-phosphorothionate receptor. Environ. Health Perspec. 61 123-132. 

Mention was made of the natural product pyrethrins and the structure of pyrethrin I was given in this chapter, Section 3.1. Because of the unique structures of these cyclopropane-containing natural products and their high insecticidal properties, syntheses of analogs have been studied. The isobutenyldimethylcyclopropanecarboxylic acid moiety, called chrysan-themic acid, has been modified by using different ester groups. As a result a number of synthetic pyrethroids are available for certain specific uses. 

Herbicides, used to kill or damage a plant, are the most rapidly growing segment of pesticides. Prior to the 1930s, herbicides were non-specific and often very toxic to humans as well as other animals. In the 1930s, in parallel with the development of new insecticides, researchers discovered several chemicals that selectively killed plants. These chemicals are now widely used to increase food production and have been used in warfare. Herbicides come in a variety of chemical structures and mechanisms of action, so they will be discussed in only general terms. Interested readers are referred to the many web sites and extensive literature on herbicides (see below and the presentation). 

Present specifications, although useful from the practical standpoint, still call for oils which are composed of numerous types of carbon structures. It would be most desirable if, through the joint effort of petroleum chemist and insect toxicologist, specifications for the ideal hydrocarbon could be established. Industry could then attempt to meet or at least approach such specifications. One is likely to reason that economics would discourage such a venture on the part of industry. However, it should be kept in mind that increased effectiveness, together with the advantages already possessed by petroleum oils, would greatly enhance their value as insecticides. 

Animals often use toxins to immobilise their prey, often insects. Wasps, bees, spiders, mites, scorpions, snakes and other reptiles are all capable of producing potent toxins many of which are insect specific. There is much work in progress around the world examining the opportunities that exist to exploit these toxins to produce new insecticides. This is usually undertaken in two different ways. The first is to determine the mode of action of the natural toxin and to use this novel effect to find synthetic compounds with insecticidal activity in biochemical screens. The second is to attempt to synthesise compounds with the same structural features of the natural toxin and hence with the same mode of action but with better stability following application. The types of compounds that are known are discussed by Blagbrough and Moya13 but none has been commercialised to date. 

SI Wie, BD Hammock. Comparison of coating and immunizing antigen structure on the sensitivity and specificity of immunoassays for benzoylphenylurea insecticides. J Agric Food Chem 32 1294-1301, 1984. 

A study of the structure of surface deposits of residual insecticides aimed specifically at bark beetle control was undertaken between 1956 and 1962 at the U.S. Forest Services Pacific Southwest Forest and Range... 

Precocenes may not provide the new approach to insect control originally expected ("4th generation" insecticides, 9) because they are not active in some major groups of agricultural pests (Lepidoptera) and because their mode of action (cytotoxicity) is not compatible with environmental concerns. Indeed, precocene II has been shown to be hepatotoxic and nephrotoxic in rats (16, 17). However, research on precocenes has led to (at least) two Important conclusions (1) compounds structurally unrelated to the JH biosynthetic pathway can reach critical sites (e.g. epoxidase) within the CA, and (2) such compounds can be catalytically processed (e.g. epoxidlzed) by enzymes of JH biosynthesis. The lax substrate specificity of methyl farnesoate epoxidase in the corpora allata and its catalytic competence might be exploited in the design of irreversible Inhibitors of JH biosynthesis (Figure 1). 

A few specific examples of cyclopropanation using the above methods are shown in Scheme 2.134. The naturally occurring insecticide /ra -chrisanthemic acid 396 served as an obvious target to check the viability of carbene addition as a preparative method. This compound was first synthesized (in the mixture with the cis isomer) by the monocyclopropanation of 2,5-dimethyl-2,4-hexadiene. Since then, numerous analogs of 396 were prepared by similar reactions. Some of the analogs are now widely used as efficient and ecologically safe pesticides. The formation of the tricyclic hydrocarbon 397 from 1,5-hexadiene proceeds as a sequence of inter- and intramolecular carbene transfer reactions. An initial carbene precursor, CHBr3, is actually employed here as an equivalent of a unique tetradentate Ci synthon The preparation of 398 via intramolecular [2 + 1] photocycloaddition is a typical example of the efficiency of this route for the construction of the polycyclic framework frequently encountered in the structures of natural compounds. 

Again, soft corals and gorgonians are a rich source of diterpenoids of 19 structural classes, some of which are specific to them (35, 36). Besides tobacco plants, cembranoid diterpenes are limited to soft corals. Lophotoxin (126) isolated from sea whips of the genus Lophogorgia is a sodium channel inhibitor (3). Xenicin (127) from the soft coral Xenia elongata and briarein A (128) from the gorgonian Briareum asbestinum represent non-cembranolide diterpenes. Diterpenoids of these classes show antimicrobial, cytotoxic, and insecticidal activities. 

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