Pyrethrin esters

There are two sites where stereospecificity must be maintained in order to achieve optimal insecticidal action. As seen in the acid moieties of the natural pyrethrin esters, all pyrethroids that possess a cyclopropane ring must have the If ... 

Begley MJ, Crombie L, Simmonds DJ et al (1974) X-ray analysis of synthetic (45)-2-(prop-2 -enyl)rethronyl (lJ )(3J )-chrysantemate 6-bromo-2,4-dinitrophenylhydrazone and (31 ) chiroptical correlation with the six natural pyrethrin esters. J Chem Soc Perkin Trans 1 879-913... 

The trans-chrysanthemic acid 88 is an essential component of naturally occurring pyrethrin esters which are present in the flower of Chrysanthenum cinera-riaefolium and has a defense function in these plants [122]. Very effective as an antifeedant for herbivores, it presents a broad spectrum as an insect repellent. 

Other antimicrobial terpenes from the Anthemideae tribe are pyrethrins. Bioassay-directed fractionation of the organic extract of Kenyan pyrethrum flowers Chrysanthemum cinerariifolium Vissiani) resulted in the isolation of two natural pyrethrin esters, pyrethrins I and II, as the major constituents [204]. These esters elicited inhibition of the multiple drug resistant Mycobacterium tuberculosis. 

A CEC separation of insecticidal pyrethrin esters was accomplished by Henry et al. [63]. Here it was shown that it is possible to identify pyrethrin esters (cinerin I, pyrethrin I, jasmolin I, cinerin II, pyrethrin II, and jasmolin II) in a commercially available pyrethrin dip and flea and tick mist (Figure 5.20). The column inner and outer diameters were 100 and 350 (im, respectively, and the total and effective lengths were 33 and 25 cm, respectively. The column was packed with 3 xm particle size Hypersil C18. The mobile phase was composed of 55 35 10, pH 9, ACN-25 mM Tris-tetrahydrofuran. Other parameters were an applied voltage of 30 kV, column temperature of 25°C, and UV detection at 254 mn. 

Pyrethrum is comprised of the dried flowers of Chrysanthemum cinerariaefolium containing not less than 1% pyrethrins. Pyrethrin esters constitute a powerful degradable contact insecticide. They have a low order of systemic toxicity to man and produce no harmful residues on food crops. The flowers and extracts for pyrethrum are imported from Kenya and... 

In the natural pyrethrin esters, the presence of two asymmetric cyclopropane carbons implies the possible existence of four stereoisomers (Deltamethrin Monograph 1982). However, in the natural pyrethrins, only the (IR, 3R) configuration exists. This fact limits the number of acids (isomers) that need to be considered in developing analytical methods for detecting pyrethrin residues in food products, or animal tissues and fluids (i.e., blood, urine, and feces). For the alcohol component, three alcohols exist pyrethrolone, cinerolone and jasmolone, and all three possess an asymmetric center that has an (S) configuration. 

The pyrethrins, esters of plant origin, long used as domestic insecticides, suffer from two defects ease of destruction by light, and provision of knockdown (a reversible general anaesthesia for the insect) rather than kill . How these defects have been overcome in recent years, through modification of the pyrethrins into pyrethroids, is told in Section y.6e. 

Many other compounds are presendy in use a 1993 database search showed 27 active ingredients in 212 products registered by the U.S. EPA for human use as repellents or feeding depressants, including octyl bicycloheptene dicarboxamide (A/-2-ethylhexylbicyclo[2.2.1]-5-hepten-2,3-dicarboxamide), dipropyl isocinchomeronate (2,5-pyridine dicarboxyhc acid, dipropyl ester), dimethyl phthalate, oil of citroneUa, cedarwood oil, pyrethrins, and pine tar oil (2). Repellent—toxicant or biting depressant systems are available which are reasonably comfortable for the user and can protect completely against a number of pests for an extended period of time (2). 

The great advance in the field of instrumentation, coupled with the discovery of the heterogeneity of the pyrethrolone radical, has advanced the knowledge of pyrethrum chemistry considerably beyond that known in 1945. LaForge and Barthel (24,25) have shown the structure of the active ingredients of pyrethrum, known collectively as pyrethrins, to be esters as represented by the structure shown in Table I. 

Recently a new constituent of pyrethrum extract was described by Godin et al. (9) jasmolin II, the cir-pent-2-enylrethronyl ester of pyrethric acid. Jasmolin II differs from pyrethrin II in that the terminal double bond of the alcoholic side chain is saturated. This constituent forms about 3% of the total pyrethrins. Jasmolin II is less toxic to the insects tested than a similar concentration of pyrethrins. The pyrethrum extract was 16 to 17 times as toxic as jasmolin II to Aedes aegypti and Fhaedon cochlearia adults, less than 17 times... 

Pyrethrins are esters and therefore may be discussed in terms of the chrysanthemumic or pyrethric moiety and the keto alcohol moiety. 

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. 

Sawicki et al. (33) prepared by reconstitution pure samples of pyrethrins I and II and cinerins I and II and compared the toxicity of these esters with the regular pyrethrum extract on houseflies 5 to 6 days old. 

Bates, Hewlett, and Lloyd (I) found that both piperonyl butoxide and SKF 525A, the ester of 2-diethylaminoethyl 2,2-diphenyl-w-pentanoate, synergized the action of pyrethrins on insects of species of the lesser mealworm beetles and houseflies but both antagonized the action of malathion. SKF 525A is known to increase the effects on mammals of drugs of various types and has been shown to synergize pyrethrins. 

Bates, Hewlett, and Lloyd (2) therefore studied the synergistic effects of some compounds related to 2-diethylaminoethyl 2,2-diphenyl-w-pentanoate on the insecticidal activity of pyrethrins. They found active compounds when a 2-diethylamino moiety was joined to the diphenylmethyl moiety through an ester, ketone, or ether linkage. However, none of the compounds investigated approached piperonyl butoxide in synergistic activity with pyrethrins. 

The columns labeled PI reflect the total of pyrethrin I and cinerin I just as in the AO AC procedure. The gas chromatographic results are in terms of the total amount of the mixture but were analyzed as the methyl ester of chrysanthemic acid. The present state of the determination of PII (pyrethrin II plus cinerin II) is not complete because of the erratic extractability of the dicarboxylic acids from the hydrolysis mixture. The gas chromatographic pattern is distinct and straightforward. As the extraction procedure for PII is improved, the gas chromatographic method will be more applicable. The present recovery of PII is in the range of 80 to 90%. The average of the values shown in Table II for PI is 98.0%. 

The compounds featured in Table 1.1 are considered briefly here. Pyrethrins are lipophilic esters that occur in Chrysanthemum spp. Extracts of flower heads of Chrysanthemum spp. contain six different pyrethrins and have been used for insect control (Chapter 12). Pyrethrins act upon sodium channels in a manner similar to p,p -DDT. The highly successful synthetic pyrethroid insecticides were modeled on natural pyrethrins. 

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... 

Pyrethrins Naturally occurring lipophilic esters that are toxic to many insects. 

Example Ester (59) was needed for a photochemical synthesis of chrysanthemate ester (60), a component of the pyrethrin insecticides. The a,B disconnection (59a) gives synthon (61) and aldehyde (62). This 8,y-unsaturated compound could be made by dehydration of (63) as the double bond can appear in only the required position. On page T 149 we discussed the synthesis of (62) by the aldol dimerisation of (64), An alternative strategy is to work at the ester oxidation level (65) which means synthon (66) is needed to combine with (64). 

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. 

The most important breakthrough in terms of modifications of the alcohol moiety of pyrethrins was the aforementioned piperonyl ester (3) followed by the inventions of resmethrin (7) by Elliott in 1965 [5] and phenothrin (5) by Itaya in 1968 [6]. Further exploratory work in Sumitomo Chemical on modification of... 

Elliott M, Famham AW, Janes NF, Soderlund DM (1978) Insecticidal activity of the pyrethrins and related compounds. Part XXI. Relative potencies of isomeric cyano-substituted 3-phenoxybenzyl esters. Pestic Sci 9 112-116... 

---