Insecticidal esters, structures

Figure 1. Structures of Six Insecticidal Esters Extracted from Pyrethrum (Chrysanthemum cinerariaefolium)...

The basis for the selective toxicity of malathlon provided the rationale for the design of the N-dlmethoxyphosphlnothloyl derivatives of methylcarbamates esters as selectively toxic Insecticides (general structure below). 

It soon became evident that the ester structure is necessary for their activity and both the acidic and the alcoholic hydrolysis products are inactive. Also the geminal methyl groups on the cyclopropane ring and the unsaturated side chains proved to favour insecticidal action. Based on these considerations Schechter et al. (1949) synthesised the ( )-3-allyl-2-methyl-4-oxo-cyclopent-2-en-l-yl ester of ( )-( ,. chrysanthemic iund (27) which became known under the name allethrin. 

Pyrethroid insecticides are generally classified into one of two large groups on the basis of the central neurotoxic syndrome that they produce [5, 6]. Type I pyrethroids are esters of chrysanthemic acid and an alcohol, having a furan ring and terminal side chain moieties, and absence of a cyano moiety. Allethrin was the first pyrethroid identified in 1949. Allethrin and other pyrethroids such as phenothrin and permethrin with the basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give ot-cyano type II pyrethroids such as deltamethrin, fenvalerate, cyfluthrin, cyhalothrin, and lambda-cyhalothrin (Fig. 137.2). 

The esters of thiosulfinic acid R -SO,-S-R are used as fungicides and antibacterial prepai ations. These compounds have similar stiaicture fragments to allicin - natural insecticide from garlic with following structure (CH =CH-CH ),[SO-S] (http //www.ALLICIN.com). For deter-mination of ethyl S-ester of 4-aminobenzenthiosulfinic acid (esulan) in the ointment RP-HPLC was proposed [1] with acetonitrile water=30 70 as eluent. For seai ching bioactive compounds the synthesis of new esters of thiosulfinic acid is perspective that was confirmed by results of recent studies as instance [2]. Therefore requirements ai e existed for investigation HPLC sepai ations of these substances. 

The acyl groups introduced included 4-phenylbenzoyl, phenylacetyl, 4-methoxybenzoyl, acetyl, 2,4-dichlorophenoxyacetyl, and 2,2-dichloropro-pionyl. Introduction of the last pair of acyl groups is important because they are bioactive (insecticides), i.e., the product can be employed in controlled-release formulations [159]. The structures of all these esters were determined by FTIR and NMR spectroscopy, whereas their solution properties, includ-... 

The structures of some pyrethroid insecticides are shown in Figure 12.1. They are all lipophilic esters showing some structural resemblance to the natural pyrethrins. They can all exist in a number of different enantiomeric forms. Permethrin, cypermethrin, and deltamethrin, for example, all have three asymmetric carbon atoms... 

The toxicity of an insecticide not only depends upon its molecular structure but also the way it is metabolised. A good example of this is Malathion (77), which is metabolised very differently by insects and humans and is therefore only toxic to insects. The mildly active Malathion (77) is rapidly oxidised in insects converting it into the strongly active oxidation product 79 (Equation 84), and this is only broken down very slowly by hydrolysis to give the weakly active 81. In contrast, oxidation of Malathion in mammals is slow, but hydrolysis of the ester group occurs very rapidly to give the inactive non-toxic compound 80 (Equation 84).1,169... 

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. 

Fujitani [6] separated the insecticidally active syrupy ester from pyrethrum flowers in 1909 and named the ester pyrethron. Yamamoto [7, 8] subjected the hydrolysis product of this pyrethron to ozone oxidation, and isolated Iram-caronic acid and aldehyde (1 and 2, respectively, Fig. 3). Although Yamamoto did not determine the structure of this acid, he presumed it to be pyrethron acid (Fig. 3). Eventually, the presence of a cyclopropane ring in the molecule of natural pyrethrins became clear for the first time in 1923. 

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. 

Research to date focused on isolating insecticidal prototype leads from marine origin has resulted in the report of about 40 active compounds.44 In an attempt to summarize these compounds and their activity margins, they have been categorized into seven classes of chemical structures polyhalogenated monoterpenes, polyhalogenated C15-metabolites, diterpenes, peptides and amino acids, phosphate esters, sulfur-containing derivatives, and macrolides. 

Estimate the Ki0Vi values at 25°C of the following compounds based on the experimental Ki0Vi values of the indicated structurally related compounds (a) benzoic acid dimethylaminoethyl ester from benzoic acid ethyl ester (log Kiaw = 2.64), (b) the insecticide methoxychlor from DDT (log Ki0Vi = 6.20), (c) the insecticide fenthion from parathion [log Kiow = 3.83, see 111. Ex. 7.2, Answer (d)], and (d) the hormone estradiol from testosterone [log Ki0Vi = 3.32, see 111. Ex. 7.2, Answer (e)]. 

Carbamates are substituted esters of carbamic acid (NH2COOH) with aliphatic or aromatic substituents on the oxygen and nitrogen atoms. Carbamate insecticides have an aryl or oxime N-methylcarbamate structure, and their mode of action is based on the inhibition of the enzyme acethylcholine esterase (1). However, this inhibition is reversible, and recovery from sublethal doses occurs rapidly. Some carbamate fungicides have a dithio, bisdithio, or benzimidazole carbamate basic structure, and dithiocarbamate fungicides inhibit the enzyme aldehyde deshydro-genase (2). The herbicides have an /V-alkylthiocarbamate or A-phenylcarbamate structure and interfere with photosynthetic activity or affect meristematic activity or lipid metabolism (3). Representative structures of carbamate pesticides are shown in Fig. 1. 

Synthetic Pyrethroid Insecticides. Elucidation of the chemical structures of the naturally occurring pyrethrum esters, their rapid and selective insecticidal action, and their high cost stimulated the search for effective synthetic derivatives (13,17,21). Since the 1940s, structural optimization has produced an array of broad-spectrum insecticides with activity 10- to 20-fold greater than other types of insecticides, and with extended residual action. These synthetic pyrethroids have become one of the most important classes of insecticides with world annual production estimated at 6000 t (21). 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive structural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-1]y 0t-cyano-(3-phenoxyphenyl)methyl (+)-(2R,T)-a-isopropyl-4-chlorophenylacetate (24) (d 1.17, vp 1.4 J,Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD ( is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(3, 3)-isomer (mp 59°C). The rat LD5Qs are 75, 458 (oral), and the rabbit dermal LD50 is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fruit crops. 

Figure 18.9 gives the structural formulas of some typical phosphorothionate esters and the general formula of this type of organophosphate insecticide. 

Synthetic pyrethroids are a group of ester compounds having excellent insecticidal activities. After the discovery of allethrin (1), a variety of useful synthetic pyrethroids have been produced mainly by structural modification of an alcohol having an asymmetric center. The insecticidal activities greatly depend upon the stereoisomers. Therefore, much effort has been expended to develop technologies for obtaining optically active isomers. However, contrary to the case of chrysanthemic acid, chemical methods of optical resolution were not very effective for these alcohols. 

Carbamate insecticides are esters of carbamic acid. The structure of carbamic acid is shown as follows ... 

O-Dealkylation O-Dealkylation of alkyl groups of the ester or ether structures of insecticides occurs frequently, but it also involves an unstable a-hydroxy intermediate as found in N-dealkylation. For example, methoxychlor is O-demethylated by the system (Figure 8.6). O-Dealkylation is known to occur with a wide variety of organophosphates, including certain dimethyl triesters. O-Dealkylation results in detoxification. 

The carbamate esters fall into two general classes according to their chemical structure and biological activity. The 7V-methylcarbamates are insecticides while the iV-arylcarbamates are mainly herbicides. Since this classification is not entirely rigorous and they are structurally related, both classes are here considered together. 

The natural pyrethrin insecticides are esters derived from the alcohols cinerolone, jasmololone, and pyrethrolone (Fig. 6). Extracts of pyrethrum, the dried flowerheads of Chrysanthemum cinerariae-folium, contain a mixture of six of these ester (Fig. 6) and are commonly available with the addition of the pyrethrum synergist piperonyl butoxide. Variations on these basic structures have... 

Pyrethroids occupy a central position among insecticides because of their high selectivity and low toxicity [34]. Chrysanthemic esters (33), the carboxylic acid components of this important class of compounds, can be synthesized by asymmetric cyclopropanation of olefins (cf Section 3.1.7) by diazoacetates in the presence of a chiral Schiff base-Cu complex (Scheme 9 and Structures 34 and 35) [35-37]. 

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