Pyrethrolone

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. 

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. 

This is interesting when one considers the effect of synergists on the synthetics. All of the synthetics mentioned above are based on chrysanthemum monocarboxylic acid and in the case of allethrin, cyclethrin, and furethrin on the alcohol moiety there is only one double bond. When checked against the standard synergists, these synthetics do not show the degree of synergism shown by pyrethrins and this may be because of the fact that there is only one double bond for epoxidation, compared with two in the pyrethrolone radical, and therefore the synergist would not block this epoxidation step as effectively. 

LaForge FB, Barthel WF (1945) Constituents of pyrethrum flowers XVIII. The structure and isomerism of pyrethrolone and cinerolone. J Org Chem 10 114-120... 

Katsuda Y, Chikamoto T, Inouye Y (1958) The absolute configuration of naturally derived pyrethrolone and cinerolone. Bull Agric Chem Soc Jpn 22 427 -28... 

Fig. 2 Two possible biosynthetic pathways to pyrethrolone. The [l-13C]D-glucose-derived 13C labels that occur in the mevalonic acid and 2-C-methyl-D-erythritol 4-phosphate (13) pathways are colored in red and green, respectively. The phosphate moiety is indicated as P ...

The alcohol moiety is produced in a different manner from that of the acid moiety. The alcohol moiety resembles the plant hormone jasmonic acid (JA) (26) generated from linolenoyl moiety of lipids via (13,S )-hydroperoxy-linolenic acid (22), (12.13,S )-epoxylinolenic acid (23), and 12-oxo-cis-10.15-phytodienoic acid (24) by the oxylipin or octadecanoid pathway (Fig. 3) [31]. In fact, 13C was incorporated at pyrethrolone (1) carbon positions that agreed with those predicted to be labeled when the alcohol moiety is produced via the pathway (Fig. 3) [30]. Figure 3 illustrates that m-jasmone (25) is hydroxylated to yield jasmololone (4), which is then dehydrogenated to yield pyrethrolone (5). However, it has not yet been determined if this is actually the case. 

Staudinger H, Ruzicka L (1924) Insektentotende Stoffe III Konstitution des Pyrethrolons. Helv Chim Acta 7 212-235... 

Pyrethrum refers to the oleoresin extracted from the dried flowers of Tanacetum cinerariaefolium (Asteraceae) and is the source of the pyrethrins, chrysanthemates and pyrethrates. Among the natural pyrethrins, those incorporating the alcohol pyrethrolone, namely pyrethrins 1 and II (Fig. 9), are the most abundant and account for most of the insecticidal activity. The pyrethrins are recommended for control of a wide range of insects and mites on fruit, vegetables, field crops, ornamentals, glasshouse crops and house plants, as well as in public health, stored products, animal houses and on domestic and farm animals. Pyrethrins are sold in a wide variety of formulations, under many different trade names by a large number of different manufacturers. 

Pyrethrum (Chrysanthemum) dnerarifolium (Asteraceae) namely cinerin I (CMC cineralone ester), cinerin II (CDC monomethyl ester cinerolone ester), pyrethrin I (CMC pyrethrolone ester) and pyrethrin II (CDC monomethyl ester pyrethrolone ester). The chrysanthemum carboxylic acids are cyclopropane-based monoterpenes and cineralone and pyrethrolone are cyclopentanone monoterpene alcohols. The pyrethrins (and their insecticidal synthetic derivatives) are toxic to insects through keeping cell membrane voltage-gated Na+ channels open and thus impairing neurotransmission. 

Pyrethrin I (= Chrysanthemum monocarboxylic acid pyrethrolone ester) (monoterpene)... 

Pyrethroids consist of pyrethrum and its synthetic pyrethrum analogs called synthetic pyrethroids. Pyrethrum is a solvent extract of dried flowers of Chrysanthemum cinerariaefo-lium. The active ingredients of pyrethrum are called pyrethrins. Pyrethrins consist of four esters, namely, pyrethrins I and II and cinerins I and II, which comprise the combination of two different alcohols (pyrethrolone and cinerolone) and two different acids (chrysan-themic acid and pyrethric acid), as follows ... 

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... 

Pyrantel embonate, 947 Pyrantel pamoate, 947 Pyrantel tartrate, 947 Pyrazinamide, 947 Pyrazinecarboxamide, 947 Pyrazinecarboxylic acid, 947 Pyrazinoic acid amide, 947 Pyrazolopyrimidinol, 327 Pyrazolylethylamine, 335 Pyrethrin I, 77, 85 Pyrethrin II, 77, 85 Pyrethrolone, 77 Pyribenzamine, 1052 Pyridacil, 873... 

This reaction was used in a synthesis of pyrethrolone (1) from butadiene (scheme... 

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