Preparation of (R)-2-(4-hydroxyphenoxy) propionic acid by biotransformation

With Beauveria bassiana Lu 700 as biocatalyst an ecologically beneficial process has been developed for the production of (R)-2-(4-hydroxyphenoxy) propionic acid. The fungal strain used in this process, B. bassiana Lu 700, is also a very suitable catalyst for the selective monohydroxylation of other aromatic carboxylic acids.     

The insecticidal and anticholinesterase activities of O,O-diethyl O-4-(2,2-disubstituted vinyl)phenyl phosphates and phosphorothioates

A series of O,O-diethyl O-4-(2,2-disubstituted-vinyl)phenyl phosphorothioates and phosphates was synthesised and examined for anticholinesterase activity to housefly and bovine erythrocyte ChE, and also for their toxicity to Musca domestica and Triatoma infestans. The synthesised phosphates were potent anticholinesterases and stronger inhibitors of housefly acetylcholinesterase than bovine erythrocyte acetyl-cholinesterase. Satisfactory correlation was obtained between the anticholinesterase activity and the Hammett σ^? constants against both enzymes, but it was not significantly improved by introducing a term for the Hansch π constant. The phosphorothioates showed poor and variable toxicity to M. domestica. On T. infestans, the only compound that showed some toxicity was the di(acetyl)-substituted product [O-4-(2-acetyl-3-oxobut-1-enyl)phenyl O,O-diethyl phosphorothioate]. For comparative studies, some commercial products were also assayed on T. infestans.     

(2E,4Z )-Decadienoic acid and (2E,4Z,7Z )-decatrienoic acid,two herbicidal metabolites from Streptomyces viridochromogenes Tü 6105

Two fatty acids, (2E,4Z)-decadienoic acid and (2E,4Z,7Z)-decatrienoic acid, the latter being described for the first time as a natural product, were detected in the culture filtrate of Streptomyces viridochromogenes Tü 6105 by HPLC-diode array screening, purified by chromatographic methods and structurally elucidated by NMR techniques. Both metabolites show strong herbicidal activity against Lemna minor and Lepidium sativum. The herbicidal activities of the isolated compounds were compared with those of similar fatty acids and derivatives. © 1999 Society of Chemical Industry     

Selectivity and mode of action of flamprop-isopropyl,isopropyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido]propionate,in the control of Avena fatua in barley

The post-emergence herbicide isopropyl (±)-2-[N-(3-chloro-4-fluorophenyl)benzamido]propionate (flamprop-isopropyl) showed good activity against wild oat with selectivity in barley. The basis for activity and selectivity was similar to that previously established for benzoylprop-ethyl, and found to be dependent on its rate of degradation to the biologically active acid flamprop. Flamprop stunted the growth of the oat by inhibiting cell elongation and showed a relatively high rate of movement in the phloem, approximately five times that of benzoylprop. Selectivity of flamprop-isopropyl was dependent on its relative rate of hydrolysis and the subsequent detoxication of the acid to inactive conjugates. However, although the relative rate of de-esterification of flamprop-isopropyl was lower than that of benzoylprop-ethyl similar quantities of the parent ester gave comparable effects on oat. The inherent activity of flamprop is approximately twice that of benzoylprop. The effect of flamprop-isopropyl was best seen when the compound was applied during growth stages when the crop could offer the most effective competition to the wild oat. Throughout a range of growth stages the rate of hydrolysis of flamprop-isopropyl was higher in oat than in barley. The metabolism of the compound was not markedly affected when the plants were under stress.     

Preparation and biocidal activity of alkyl phenyl (dichloromethyl)phosphonates

Seventeen new alkyl (or phenacyl) phenyl (dichloromethyl)phosphonates were synthesised; seven of these showed poor fungicidal activity when tested in vitro against Pyricularia oryzae but some possessed high insecticidal activity against Culex fatigans and Drosophila melanogaster.     

Animal metabolism of propham (isopropyl carbanilate): The fate of residues in alfalfa when consumed by the rat and sheep

Alfalfa was root-treated with [¹⁴C]propham (isopropyl carbanilate[¹⁴C-phenyl(U)]) for 7 days and then harvested and freeze-dried. Rats and sheep were orally given either ¹⁴C-labeled alfalfa roots ([¹⁴C]root) or ¹⁴C-labeled alfalfa shoots ([¹⁴C]shoot). When the [¹⁴C]root was given, 6.5–11.0% of the ¹⁴C was excreted in the urine and 84.6–89.4% was excreted in the feces within 96 h after treatment. Less than 3% of the ¹⁴C remained in the carcass (total body—gastrointestinal tract and contents) 96 h after treatment. When [¹⁴C]shoot was given, 53.2–55.2% of the ¹⁴C was excreted in the urine, 32.1–43.4% was excreted in the feces, and the carcass contained 0.2–1.1% of the ¹⁴C 96 h after treatment. When the insoluble fraction (not extracted by a mixture of CHCl₃, CH₃OH, and H₂O) of both alfalfa roots and shoots was fed to rats, more than 86% of the ¹⁴C was excreted in the feces and less than 3% remained in the carcass 96 h after treatment. The major radiolabeled metabolites in the urine of the sheep fed ¹⁴C shoot were purified by chromatography and identified as the sulfate ester and the glucuronic acid conjugates of isopropyl 4-hydroxycarbanilate. Metabolites in the urine of the sheep treated with [¹⁴C]root were tentatively identified as conjugated forms of isopropyl 4-hydroxycarbanilate, isopropyl 2-hydroxycarbanilate, and 4-hydroxyaniline. The combined urine of rats dosed with [¹⁴C]shoot and [¹⁴C]root contained metabolites tentatively identified as conjugated forms of isopropyl 4-hydroxycarbanilate, isopropyl 2-hydroxycarbanilate, and 4-hydroxyaniline.     

Effects of acute and multiple dose administration of Sumithion (O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothionate) on some enzymes of Periplaneta americana (Linn.)

Acute exposure to Sumithion (65.0 μg/g dose) causes significant inhibition of acetylcholinesterase (AChE) in the digestive tissue of adult P. americana. At this dose there is practically no effect on the activities of either acid or alkaline phosphatases or non-specific esterases. Exposures to multiple doses of 1.3 μg/g at intervals of 24 and 48 hr, respectively, lower AChE activity by approximately 40%. On the other hand multiple doses cause an initial rise in the activities of phosphatases, indicating their possible involvement in the metabolism of the pesticide. However, later on, there is a decrease in levels of acid and alkaline phosphatase activities. This is coupled with a steady rise in nonspecific esterase activity indicating a possible take over of metabolizing role by these enzymes.     

Determination of individual esters of 2, 4-D and 2, 4, 5-T in commercial crops

A rapid gas chromatographic method for the determination of the individual esters of 2, 4-D and 2, 4, 5-T in tomato plants and other commercial crops is described. Several suitable esters can be determined at one time. Separation is by steam distillation into a hexane trap followed by clean-up on a column of “Florisil”. Using a sample of plant material (100 g), 1 μg of each of the esters in the mixture can be determined with recoveries of 72–96% for 2, 4-D esters and 66–84% for 2, 4, 5-T esters.     

Inhibition of ergosterol biosynthesis in Ustilago maydis by the fungicide 1-[2-(2, 4-dichlorophenyl)-4-ethyl-1, 3-dioxolan-2-ylmethyl]-1H-1, 2, 4-triazole

Inhibition of sporidial multiplication in cultures of Ustilago maydis by 1-[2-(2, 4-dichlorophenyl)-4-ethyl-1, 3-dioxolan-2-ylmethyl]-1H-1, 2, 4-triazole^a (CGA-64251), at concentrations of 0.1, 1.0 and 5.0 μg ml^?1, increased from about 15% during the first 4 h, to 58–70% during the subsequent 4 to 12-h period. Sporidia became swollen and highly branched in the presence of the fungicide. Total lipid content as a percentage of the dry weight was not affected after exposure of the sporidia to the fungicide at 0.1 or 5 μg ml^?1 for 4 h, but synthesis of ergosterol and other demethyl-sterols was inhibited by 87–92%. Large quantities of methyl-sterol precursors of ergosterol and of free fatty acids accumulated in the treated sporidia. Fungitoxicity of CGA-64251 is attributed to inhibition of ergosterol biosynthesis at the stage of sterol C-14 demethylation.     

Studies on pesticides based on coumarin IV: Synthesis and antifungal activity of twelve 4-(substituted phenoxy)methyl-6-methyl coumarins

Twelve 4-(substituted phenoxy)methyl-6-methyl coumarins were synthesised by the condensation of 4-chloromethyl-6-methyl coumarin with various phenols in the presence of potassium carbonate in dry acetone. The compounds were tested for their toxicity towards the mycelial growth of seven plant pathogenic fungi. Among the tested fungi, Pythium aphanidermatum, Colletotrichum falcatum, Drechslera oryzae, Alternaria alternata and Fusarium solani exhibited maximum sensitivity whereas Macrophomina phaseolina and Rhizoctonia solani were least sensitive to the test compounds. The 4-(4-tert-butylphenoxy)methyl and 4-(4-nitrophenoxy)methyl analogues possessed greatest toxicity towards the majority of the tested fungi.     

Herbicide perfluidone (1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide): Its metabolism in rats and chickens

Rats and chickens were each given a single oral dose (10 or 100 mg/kg body wt) of 1,1,1-trifluoro-N-[2-methyl-4-(phenylsulfonyl)phenyl-¹⁴C(U)]methanesulfonamide ([¹⁴C]perfluidone). Depending on the size of the dose, from 8.4 to 36.2% of the [¹⁴C] was eliminated in the urine and from 36.4 to 85.4% was eliminated in the feces within 48 hr after dosing. Less than 1% of the [¹⁴C] given to laying hens as [¹⁴C]perfluidone was present in the eggs produced during the first 96 hr after dosing. The percentage of the administered [¹⁴C] that remained in these animals (body with G.I. tract and contents removed) varied from 0.34 (96 hr after dosing) to 1.68% (48 hr after dosing). ¹⁴C-labeled compunds in the urine and feces from the rats and chickens were purified by solvent extraction, column chromatography, and gas-liquid chromatography, and then identified by infrared and mass spectrometry. The parent compound was the major ¹⁴C-labeled component in the urine and feces of both animals. 1,1,1-Trifluoro-N-[2-methyl-4-(3-hydroxyphenylsulfonyl)phenyl]methanesulfonamide was present in the feces of both animals. The proposed structures of other metabolites were 1,1,1-trifluoro-N-hydroxy-N-[2-methyl-4-(phenylsulfonyl)phenyl]methanesulfonamide (rat urine) and 1,1,1-trifluoro-N-{2-methyl-4-[(methylsulfonyl)-phenylsulfonyl]phenyl}methanesulfonamide (chicken urine).     

Benomyl and methyl-2-benzimidazolecarbamate (MBC): Biochemical,cytological and chemical aspects of toxicity to Ustilago maydis and Saccharomyces cerevesiae

Action of methyl-2-benzimidazolecarbamate (MBC), a breakdown product of benomyl, was studied in synchronous cultures of Ustilago maydis and Saccharomyces cerevesiae. Cells treated with MBC developed similarly to control cells until the two portions of the doublets (joined mother and daughter “cells”) were morphologically equivalent. At this point development of the treated cells ceased but control doublets separated to form two new cells. The compound did not prevent DNA synthesis during the first cell cycle of synchronized S. cerevesiae cells but did prevent completion of cell division, as it did also in synchronized U. maydis sporidia which already contained the DNA complement needed for completion of the first division. Mitosis did not go to completion in MBC-treated cells so the doublets formed contained only a single compact nucleus. The effect of MBC markedly resembles mitotic arrest caused by colchicine and isopropyl N-phenylcarbamate in higher plants and griseofulvin in the fungus Aspergillus nidulans. Inhibition of DNA synthesis in U. maydis and inhibition of cytokinesis in both organisms studied are secondary effects attributable to mitotic failure.A volatile compound toxic to U. maydis and S. cerevesiae was demonstrated in air over moistened benomyl. Hexane, through which such air samples were passed, or hexane extracts of aqueous suspensions of benomyl contained a substance having the same ir spectrum and retention time in two gas chromatographic systems as butyl isocyanate (BIC).BIC inhibited respiration of U. maydis and S. cerevesiae in a manner similar to benomyl. Benomyl partially inhibited respiration of subcellular particles from both organisms. MBC had essentially no effect on whole cell or subcellular particle respiration of either organism. Toxicity of benomyl preparations is not attributed to “benomyl” as such, but to two breakdown products, MBC and BIC. Therefore, differential effects of benomyl preparations and of MBC on growth and metabolism in fungi should be ascribed to BIC.     

Synthesis and insecticidal properties of some 2-substituted-3-oxo-4-halo-5(2H)-pyridazinyl phosphorus esters

A series of novel esters of organophosphorus compounds were prepared from 2-substituted-4-halo-5-hydroxy-3(2H)-pyridazinone and their insecticidal effects were studied. Many of the compounds prepared showed insecticidal and acaricidal contact activity.     

Synthesis and plant growth regulating properties of derivatives of alkyl 3-benzoyl-3-(3-chloro-4-substituted phenyl)-2-methylcarbazates

Alkyl 3-benzoyl-3-(3-chloro-4-substituted-phenyl)-2-methylcarbazates (isoelectronic analogues of wild oat herbicides) have plant growth regulating properties for various weeds and crops. Some derivatives of carbazates, bearing halogen in the 4-position of the phenyl group, have been shown to have the highest activity of the prepared compounds.     

Dissipation of 4-chloro-2-methylphenoxyacetic acid (MCPA) in a rice field

The dissipation of the herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA) in a California rice field was investigated. Samples of water, rice plants and mud were collected at intervals for 20 days and analysed for MCPA by established methods for plants and mud, and by a novel method utilising XAD-2 macro-reticular resin for water. Water residues declined to less than 0.01 parts/10⁶ of MCPA within 14 days after application; plant residues declined from 20 parts/10⁶ to 1 part/10⁶ within 20 days; mud residues remained constant at about 0.1 parts/10⁶. Photolysis of dilute aqueous MCPA solutions with either sunlight or an indoor photoreactor yielded 4-chloro-2-methylphenol as the major product; o-cresol and 4-chloro-2-formylphenol also were identified. While photosensitisation was observed with water taken from the rice field, microbial degradation proceeded at an even faster rate. All environmental compartments except air contained measurable amounts (>0.01 parts/10⁶) at some time, but water contained the bulk of the applied MCPA whose eventual disappearance was shown to be due to biological and chemical degradation and not dilution.     

Effect of 4-amino-6-methyl-3-phenylamino-l,2,4-triazin-5(4H)-one on the lignification process catalysed by peroxidase from lupin (lupinus albus)

The molecular action of herbicides with a triazine structure, such as atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) and metribuzin (4-amino-6-tert-butyl-3-methylthio-1,2,4-triazin-5(4H)-one), has been related to their inhibition of the electron carrier system between chloroplastic photosystems II and I. This report provides evidence that 4-amino-6-methyl-3-phenylamino-1,2,4-triazin-5(4H)-one, a recently synthesised triazine, structurally analogous to metribuzin, causes a powerful inhibition of the cell-wall lignification catalysed by peroxidase from lupin. The two reactions involved in this lignification process are: oxidative polymerisation of coniferyl alcohol and the generation of hydrogen peroxide at the expense of NADH oxidation.     

Interference of benomyl and methyl-2-benzimidazolecarbamate (MBC) with DNA metabolism and nuclear divisions in Fusarium oxysporum

Methyl-1-(butylcarbamoyl)-2-benzimidazolecarbamate (benomyl) severely decreased DNA synthesis when applied at 3.5 × 10^?6M during the G1 phase of germinating conidia of Fusarium oxysporum; nuclear divisions were completely inhibited at a fungicide concentration of 10 × 10^?6M. The same concentration applied only after the S phase also completely inhibited the nuclear divisions. This dual interference of benomyl with DNA formation and mitosis might be related to a disturbed phosphorus metabolism.     

Residues of the carbamate acaricide, 3-methyl-5-isopropylphenyl-N(n-butanoyl)-N-methylcarbamate (promacyl) and two metabolites in the tissues and milk of cattle

In order to assess some of the residue characteristics of the experimental carbamate acaricide, 3-methyl-5-isopropylphenyl-N-(n-butanoyl-)-N-methylcarbamate (promacyl) a 0.2 % aqueous emulsion was applied to cattle in a series of five trials and in a sixth, the technical product was added to the feed of stalled cattle. A method of analysis involving the formation of a derivative suitable for gas chromatographic analysis on electron capture detection mode was developed. Separate estimations of levels of the parent compound and the metabolites, 3-methyl-5-isopropylphenyl -N-methylcarbamate and 3-methyl-5- isopropylphenol, were carried out on fatty tissues and butterfat but for non-fatty tissues “total” levels, which were a combined estimate of 3-methyl-5-isopropylphenol itself and all substances hydrolysable to it, were estimated and quoted as Promacyl. The highest group average level of the parent compound was 0.9 part/million in fatty tissues 24 h after the last of 8 applications at 3 day intervals. In a single spray trial the maximum group average of 0.7 part/million in fatty tissues 24 h after treatment fell to 0.2 part/million after 5 days. Residues in butterfat, 7 h after a single dermal application showed a maximum level of 1.2 parts/million and this declined to 0.1 part/million on the seventh day after treatment. “Total” residues in non-fatty tissues were of the order of 1/10 those found in fatty tissues.     

Inhibition of acetyl-coenzyme a carboxylase by the novel grass-selective herbicide 3-(2,4-dichlorophenyl)-perhydroindolizine-2,4-dione

The novel herbicidal compound 3-(2,4-dichlorophenyl)-perhydroindolizine-2,4-dione which is active as a pre- and post-emergence grass-selective herbicide is a new type of inhibitor of plant acetyl-coenzyme A carboxylase (ACCase; E.C. 6.4.1.2). This has been demonstrated by in-vitro experiments using isolated corn enzyme. Besides an I₅₀ value of 4.7 μM under the assay conditions used, a mixed-type inhibitory activity on the enzyme is established. The compound is inactive on rat liver A CCase enzyme and shows decreased activity (pI₅₀ less than 3.0) on the spinach enzyme.     

Inhibition of DNA synthesis in boll weevils (Anthonomus grandis boheman) sterilized by dimilin

When boll weevils, Anthonomus grandis Boheman, were treated with dimilin (N-(4-chlorophenyl)-N′-(2,6-difluorobenzoyl)urea), the biosynthesis of deoxyribonucleic acid was inhibited in the female, but neither ribonucleic acid nor protein synthesis was affected. Treated males showed a difference in effect in lipoprotein synthesis, whereas no significant difference was demonstrated with females. Testicular growth was inhibited in some of the males. Diminishment of sexual function may therefore result in part from inhibition of biosynthesis of DNA by dimilin.