The pyrethrins and related compounds. XVII. Preparation of the insecticide bioresmethrin (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate) and related compounds labelled with deuterium or tritium on the furan ring

2-²H-5-Benzyl-3-furylmethyl esters exclusively are obtained from an exchange reaction of the parent esters with deuterium oxide and a trace of acid (n.m.r. and mass spectrometric control). Similarly, with tritiated water, 6 insecticidal esters of 5-benzyl-3-furylmethyl alcohol give the corresponding [2-³H]esters, each with specific activity of approx. 500 mCi/mmol.     

Extensive pilot use of the grain protectant combinations,fenitrothion plus bioresmethrin and pirimiphos-methyl plus bioresmethrin

Each of the combinations, bioresmethrin (1 mg kg^?1) plus pirimiphos-methyl(6 mg kg^?1) or fenitrothion (12 mg kg^?1), was applied in 1976 to grain in 21 commercial storages. Grain condition and protectant residues were regularly monitored. Three storages became infested with Rhizopertha dominica (F.), but all storages remained free of other insect species. In two of the three infested storages, application of protectant was uneven, and the third became infested only after 8 months of storage. Despite some variations in recovered residues between sites, the mean residue levels were accurately described by predictive models. Falls in temperature during storage varied considerably, and were related to factors other than climate and bin size. There was a marked effect by aeration with ambient cold air on both the grain temperature and the rate of loss of residues. Results of collaborative studies on the determination of residues indicate a need for regular check programmes of analysis, and confirm previous conclusions that residues of fenitrothion and pirimiphos-methyl can be accurately and conventionally determined.     

The pyrethrins and related compounds; Part XXIII:Kinetic control in the formation of pyrethroidal estersb

The unequal amounts of the two diastereomers of (RS)-1-(3-phenoxyphenyl)ethyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate, obtained from equimolar proportions of the alcohol and acyl chloride under normal conditions, imply stereoselectivity in the reaction. The extent to which this depends on the nature of the α-substituent for arange of 3-phenoxybenzyl esters, on the nature of the acid, and on the method of esterification is investigated. Selectivity arises from kinetic, rather than thermodynamic control.     

Action of bioresmethrin on the corpus cardiacum of Locusta migratoria

The action of the pyrethroid insecticide bioresmethrin on the corpus cardiacum (CC) has been studied in Locusta migratoria. Bioresmethrin increased the spontaneous electrical activity recorded from both the glandular and storage lobes, and induced repetitive discharge in these lobes in response to single electrical stimulation of the nervus corpus cardiacum II (NCC II) and NCC I, respectively. Incubation of the isolated CC in low concentrations of bioresmethrin (0.1-1.0 μmol) induced the release of bioassayable hyperlipaemic hormone. Injection of bioresmethrin into locusts was found to induce an elevation in the haemolymph lipid at a stage when there was no overt symptom of poisoning. It is concluded that bioresmethrin may act directly on the CC of locusts to modulate electrical activity and induce the release of hormones. The effects may precede overt symptoms of poisoning.     

Phytotoxicants from microorganisms and related compounds

Phytotoxic compounds produced by microorganisms are reviewed. Their utilisation as leads to new herbicides is explored in three chemical classes : 2-aminoalk-3-enoic acids, ether derivatives of 3-hydroxycyclobut-3-ene-1,2-diones, and 2-(acylaminooxy)acetic acid derivatives. It is concluded that some bacteria and fungi yield compounds possessing sufficient herbicidal activity to be valuable as herbicides as such, or as leads for chemical optimisation.     

Photodecomposition of natural pyrethrins and related compounds

Present knowledge of the photochemistry of the pyrethrins, and of the alcohols and acids from which they are constituted is summarised.     

The relationship between the pharmacokinetics of intravenous cismethrin and bioresmethrin and their mammalian toxicity

The distribution and excretion of [¹⁴C]alcohol-labeled cismethrin and bioresmethrin was determined after intravenous administration to rats. Initially the label distribution of both isomers was similar, but differences occurred at later times mainly due to the retention of 5-benzyl-3-furylcarboxylic acid, a metabolite of bioresmethrin, in high concentration in the blood. Retention of this metabolite accounted for the slower excretion of bioresmethrin label compared to cismethrin. After administration of either isomer, parent pyrethroid was rapidly cleared from the blood and liver, and both isomers rapidly entered the central nervous system reaching peak concentrations within 2–5 min. Brain cismethrin concentrations exceeding 3.5 nmol/g were associated only with animals showing tremors. These levels of cismethrin are maintained for up to 30 min but bioresmethrin was depleted more rapidly possibly due to brain metabolism. It is concluded that the low toxicity of bioresmethrin is possibly due to the inability of this isomer to interact with the site of action in the central nervous system and not, as previously suggested, primarily because of more rapid metabolism in the liver.     

Soil sensitised generation of singlet oxygen in the photodegradation of bioresmethrin

The ability of soil samples of pH 4·2, 5·5 and 7·2 to generate gaseous singlet oxygen was investigated using a separated-surface-sensitised reactor. It was found that the soil samples can act as sensitisers for the production of singlet oxygen in a similar fashion to the well known sensitisers chlorophyll and Rose Bengal. The reaction of singlet oxygen so produced with the pyrethroid insecticide, bioresmethrin, has been investigated.     

Disinsection of aircraft with pressure packs containing the pyrethroids,resmethrin and bioresmethrin

Pyrethrins and the pyrethroids, bioallethrin ((+) trans-chrysanthemic acid ester of (±) allethrolone), resmethrin* (5-benzyl-3-furylmethyl (±)-cis,trans-chrysanthemate) and bioresmethrin? (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate) were compared for insecticidal activity against free-flying Aedes aegypti L. in a Peet-Grady chamber using kerosene solutions and an aerosol particle size. The relative potency for kill of female mosquitoes was 1; 2.3; 6.8; 8.0 respectively. In further experiments, resmethrin and bioresmethrin were compared as aerosol formulations in a Comet 4C aircraft using caged and fed female A. aegypti. Both compounds at 0.1% (by wt.) in pressure packs and 35 g of formulation per 100 m³ provided 99% kill. It is suggested that pressure packs containing 0.5% (by wt.) of either compound should be adequate for disinsection of passenger aircraft. However, bioresmethrin would appear to be the compound of choice in view of its greater biological efficiency under laboratory conditions, and consequent probable greater margin of kill in practice.     

The rodenticidal activity of reserpine and related compounds

The spread of warfarin resistant mice in the early 1970s prompted an urgent search for alternative rodenticides suitable for commercial use. The early success of a stupefying compound, chloralose (alphachloralose), directed research in that direction and led ultimately to the adoption of reserpine as a rodenticide. Laboratory and field trials of reserpine, and some of its naturally occurring and synthetic analogues, against mice and rats, are reported here.     

Selective complexometric determination of glyphosate and related compounds

A complexometric method has been developed for the selective determination of glyphosate and related compounds. The method is based upon the different pH-dependence of tridentate and tetradentate ligand-metal complex stabilities. Glyphosate, the tridentate ligand forms a stable copper complex at pH ≥ 8 only, whereas N-carboxymethyl-N-phosphonomethylglycine and N,N-bis(phosphonomethyl)glycine, the tetradentate ligands, form sufficiently stable bismuth complexes even at low pH. The method, therefore, consists of aliquot titrations in basic and acidic media, using metal ion titrant solutions. The first aliquot containing N-(phosphonomethyl)glycine plus N-carboxymethyl-N-phosphonomethylglycine or N,N,-bis(phosphonomethyl)glycine is titrated with bismuth volumetric solution at pH 1.8–2–5 in the presence of methylthymol blue indicator. Quantities of the tetradentate ligands can be calculated from the bismuth consumption. The second aliquot is titrated with copper volumetric solution at pH 8–10, in the presence of murexide indicator. The content of glyphosate can be calculated from the difference between the copper and bismuth consumptions. Efficacy of the method is verified by analyses of standard mixtures and industrial samples.     

Insecticidal activity of 3-isoxazolyl methanesulfonates and related compounds

Various methanesulfonates, notably of 3-isoxazolols, exhibit interesting insecticidal activity, especially against Musca domestica and Locusta migratoria. Although the symptoms of poisoning are very similar to those caused by parathion, no correlation between in-vitro inhibition of acetylcholinesterase and insecticidal activity was observed. This is also true for several methanesulfonates of hydroxy-heterocycles and phenols included in this study for comparison.     

The pyrethrins and related compounds. Part XXV: Synthesis and insecticidal activity of conformationally restrained compounds related to 3-phenoxybenzyl esters

Derivatives of 3-phenoxybenzyl pyrethroidal esters were synthesised in which rotation about the benzylic C-1–C-α bond was restricted by an additional bridging ring. The insecticidal activities of these compounds to houseflies (Musca dornestica) and mustard beetles (Phaedon cochleariae) depended on the size of the bridging unit and on whether it joined C-α to C-2 or C-6 of the benzyl nucleus. The results obtained are considered in relation to current correlations of the structures with the activities of pyrethroids.     

Synthesis of 1,2,4-triazole compounds related to the fungicides flutriafol and hexaconazole

Triazole and imidazole compounds are important both as pharmaceutical and agrochemical fungicides. It has been demonstrated that they exhibit this activity because they inhibit the 14 α-demethylase enzyme involved in the biosynthesis of fungal sterols. A knowledge of the mode of action of the triazoles paclobutrazol, diclobutrazol and propiconazole has made it possible to devise inhibitors of the 14 α-demethylase enzyme somewhat more readily, using computer graphic techniques. These techniques were used in the discovery of flutriafol, one of the first examples of a triazole tertiary alcohol structure. They also assisted in identifying other triazole tertiary alcohol structures for testing as fungicides. Hexaconazole is one example of a highly active broad-spectrum fungicide. Modification of the hexaconazole structure has produced many other active fungicides, many of which can be conveniently synthesised by the addition of organometallic (e.g. lithium, magnesium, aluminium, titanium or zinc) reagents to α-1,2,4-triazol-1-yl ketones or α-haloketones. Alternatively, they can be prepared by the reaction of nucleophiles such as mercaptans, nitrogen heterocycles or organometallic (e.g. magnesium) reagents with epoxides.     

Synthesis of new compounds related to the commercial fungicide tricyclazole

BACKGROUND: Tricyclazole is a commercial fungicide used to control rice blast. As part of re‐registration activities, samples of metabolites and process impurities are required. In addition, isotopically labeled tricyclazole samples are also required. RESULTS: Four new compounds related to tricyclazole are reported. An isotopically labeled sample of tricyclazole was prepared that contained two ¹⁵N atoms and one ¹³C atom. Radiolabeled tricyclazole with ¹⁴C at the triazole C3 position was also synthesized. A new process impurity in technical tricyclazole was identified and synthesized. A new metabolite of tricyclazole was identified, independently synthesized and characterized by X‐ray crystallography. CONCLUSION: A previously unreported metabolite of tricyclazole has been identified and structurally characterized. In addition, a new process impurity has been identified by independent synthesis. Identification of these new compounds has facilitated the continued registration of this important fungicide. Copyright © 2011 Society of Chemical Industry     

The pyrethrins and related compounds. Part XXVII. Esters of pulegenic and related acids

A report by Staudinger and Ruzicka of the insecticidal activity of an ester of pulegenic acid with mixed naturally derived alcohols had not been examined further, and had been misinterpreted in a review. Therefore, two isomeric pulegenic and nine related acids were synthesised, characterised and esterified with modern, more effective, pyrethroidal alcohols. The pulegenic esters were inactive, but low activity was found in esters of acids in which the 5-membered ring was additional to, rather than a replacement for, the cyclopropane ring.     

Simultaneous estimation of bioresmethrin and piperonyl butoxide by gas-liquid chromatography with chemical-ionisation mass spectrometry

A technique using gas-liquid chromatography combined with chemical-ionisation mass spectrometry is described for the simultaneous quantitative measurement of bioresmethrin and piperonyl butoxide. It is sensitive to 0.2 ng bioresmethrin and 2 ng piperonyl butoxide. The amounts of these compounds, in extracts of 50-g samples of laboratory-fortified wheat, were determined.     

The incorporation of DDT and related compounds into lecithin bilayers

The incorporation of DDT and several analogs into the hydrophobic interior of lecithin bilayers has been monitored by observing the nuclear magnetic resonance spectra of the aromatic ring protons. A fluid bilayer interior was obligatory for the incorporation of the chemicals. The amount of the different compounds which can be taken up into the lipid in aqueous media varies significantly, and this difference is not related to the organic: aqueous partition coefficients of the analogs. The amount of DDT, the most nonpolar of the compounds studied, which could be incorporated into the bilayers was much lower than the levels of other, more water-soluble analogs.     

Polyclonal and monoclonal antibodies for the specific detection of the herbicide acifluorfen and related compounds

Polyclonal and monoclonal antibodies reactive with acifluorfen (AF) were prepared by the immunization of, respectively, rabbits and mice with AF-bovine serum albumin conjugates. The reactivities of polyclonal antibody and three monoclonal antibodies (AF 9-1, AF 51-5 and AF 75-144) were examined in an indirect competitive enzyme-linked immunosorbent assay (C-ELISA). The polyclonal antibody reacted with AF at concentrations of 1·5 to 800 μg litre^-1, while the monoclonal antibodies reacted with AF at concentrations of 3 to 24 μg litre^-1 for AF 9-1, 1·5 to 12 μg litre^-1 for AF 51-5 and 12 to 48 μg litre^-1 for AF 75-144. In the presence of up to 40% methanol in C-ELISA, the monoclonal antibodies, particularly AF 75-144, were less affected in their reactivities with AF than was the polyclonal antibody. Moreover AF 9-1 and AF 51-5 specifically reacted with acifluorfen-methyl and oxyfluorfen, while AF 75-144 reacted with chlornitrofen which did not react with the other antibodies. These results indicated that the antibodies are useful for the assay of AF and its related compounds. © 1997 SCI.