Phthalic Acid Diamide Research Articles

Molecular Characterization of a Ryanodine Receptor Gene in the Rice Leaffolder, Cnaphalocrocis medinalis (Guenée)

Ryanodine receptors (RyRs) are the targets of two novel classes of synthetic insecticidal chemicals, phthalic acid diamides and anthranilic diamides. Isolation of full-length RyR cDNAs is a critical step towards the structural and functional characterization of insect RyRs and an understanding of the molecular mechanisms underlying the species selective toxicity of diamide insecticides. However, there has been little research on the insect RyR genes due to the high molecular weight of the RyR proteins. In this study, we isolated a full-length RyR cDNA (named as CmRyR) from Cnaphalocrocis medinalis, an important rice pest throughout Southeast Asia. The composite CmRyR gene contains an ORF of 15264 bp encoding a protein of 5087 amino acid residues, which shares 79% overall identity with its Drosophila melanogaster homologue. All hallmarks of the RyR proteins are conserved in the CmRyR protein, suggesting that CmRyR is a structural and functional analogue of known RyRs. A multiple sequence alignment illustrates that the insect RyRs share high levels of amino acid sequence identity at the the COOH-terminal region. However, the amino acid residues analogous to the CmRyR residues N4922, N4924, N4935, L4950, L4981, N5013 and T5064 are unique to lepidopteran RyRs compared with non-lepidopteran insect RyRs. This finding suggests that these residues may be involved in the differences in channel properties between lepidopteran and non-lepidopteran insect RyRs and in the species selective toxicity of diamide insecticides. Furthermore, two alternative splicing sites were identified in the CmRyR gene, one of which was located in the central part of the predicted second SPRY domain. Diagnostic PCR showed that the inclusion frequencies of two mutually exclusive exons (a/b) and one optional exon (c) differed between developmental stages or adult anatomical regions. Our results imply that alternative splicing may be a major means of generating functional diversity in C. medinalis RyR channel.

Rhodium‐Catalyzed Asymmetric Hydrogenation of Olefins with PhthalaPhos, a New Class of Chiral Supramolecular Ligands

A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (PhthalaPhos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2-acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1-yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3-phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.

Synthesis, Insecticidal Activity, and Structure−Activity Relationship of Trifluoromethyl-Containing Phthalic Acid Diamide Structures

Phthalic acid diamides have received considerable interest in agricultural chemistry due to a novel action mode, extremely high activity against a broad spectrum of lepidopterous insects, low acute toxicity to mammals, and environmentally benign characteristics. A series of phthalic acid diamides (4I-4IV) with the CF3 group at meta position on the aniline ring were synthesized. Their structures were characterized by (1)H NMR and (13)C NMR (or elemental analysis). The structure of N(2)-[1,1-dimethyl-2-(methylthio)ethyl]-3-iodo-N(1)-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2-benzenedicarboxamide (4If) was determined by X-ray diffraction crystallography. Their insecticidal activities against Plutella xylostella were evaluated. The results show that some of the title compounds exhibit excellent larvicidal activities against P. xylostella, and improvement in larvicidal activity requires a reasonable combination of substituents in the parent structure, which provides some hints for further investigation on structure modification.

Dissipation kinetics of flubendiamide and thiacloprid on tomato (Lycopersicon esculentum Mill) and soil

Introduction Flubendiamide, a phthalic acid diamide widely used against the lepidopteran pests and thiacloprid, the first chloronicotinyl insecticide quite effective against the sucking insects, white flies and jassids have recently been used on various vegetable crops in India. Objectives Studies on dissipation kinetics of insecticides is very essential to work out their half- lives and waiting periods for the safe consumption of agricultural produce. Methods Standardized methodology supported by recovery studies is adopted to estimate residues of flubendiamide and thiacloprid on tomato. Final estimation of residues was accomplished using high performance liquid chromatography by employing C18 column and photo diode array at 230 wavelength. Results Half-lives values for flubendiamide following its three applications at 10 days intervals @ 48 g a.i. ha−1 were observed to be 0.33 and 1.00 days, respectively. Similarly, at the same application rate these values for thiacloprid were found to be 1.18 and 0.95 days, respectively. Flubendiamide and thiacloprid residues were observed to dissipate below their determination limit of 0.01 mg kg−1 after 3 and 5 days, respectively, when applied @ 48 g a.i.ha−1. Soil samples collected after 15 days did not show the presence of flubendiamide, desiodo flubendiamide, and thiacloprid at their determination limit of 0.01 mg kg−1. Conclusion A waiting period of 5 days is recommended for safe consumption of tomato fruit after application of combination formulation of flubendiamide 24%+thiacloprid 24% (480 SC) @ 200 g ha−1.

Insect ryanodine receptors: molecular targets for novel pest control chemicals

Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the sarcoplasmic reticulum of muscle and the endoplasmic reticulum of neurons and many other cell types. Ryanodine, a plant alkaloid and an important ligand used to characterize and purify the receptor, has served as a natural botanical insecticide, but attempts to generate synthetic commercial analogues of ryanodine have proved unsuccessful. Recently two classes of synthetic chemicals have emerged resulting in commercial insecticides that target insect RyRs. The phthalic acid diamide class has yielded flubendiamide, the first synthetic ryanodine receptor insecticide to be commercialized. Shortly after the discovery of the phthalic diamides, the anthranilic diamides were discovered. This class has produced the insecticides Rynaxypyr and Cyazypyr. Here we review the structure and functions of insect RyRs and address the modes of action of phthalic acid diamides and anthranilic diamides on insect ryanodine receptors. Particularly intersting is the inherent selectivity both chemical classes exhibit for insect RyRs over their mammalian counterparts. The future prospects for RyRs as a commercially-validated target site for insect control chemicals are also considered.

Phthalic acid diamides activate ryanodine-sensitive Ca 2+ release channels in insects

Flubendiamide represents a novel chemical family of substituted phthalic acid diamides with potent insecticidal activity. So far, the molecular target and the mechanism of action were not known. Here we present for the first time evidence that phthalic acid diamides activate ryanodine-sensitive intracellular calcium release channels (ryanodine receptors, RyR) in insects. With Ca 2+ measurements, we showed that flubendiamide and related compounds induced ryanodine-sensitive cytosolic calcium transients that were independent of the extracellular calcium concentration in isolated neurons from the pest insect Heliothis virescens as well as in transfected CHO cells expressing the ryanodine receptor from Drosophila melanogaster. Binding studies on microsomal membranes from Heliothis flight muscles revealed that flubendiamide and related compounds interacted with a site distinct from the ryanodine binding site and disrupted the calcium regulation of ryanodine binding by an allosteric mechanism. This novel insecticide mode of action seems to be restricted to specific RyR subtypes because the phthalic acid diamides reported here had almost no effect on mammalian type 1 ryanodine receptors.

１，１，１‐トリクロロエタンとアルミニウムとの反応の多価フェノール類，ジアミド類およびイミド類添加による阻害作用

The retarding effect (RE) of various organic reagents on the reaction beween 1, 1, 1-trichloroethane (CCl3·CH3) and aluminum was investigated by measuring the induction period of the reaction. In the previous paper, it was confirmed that the RE of compounds having two functional groups increased 5-100 times over that of compounds having one functional group. However, contrary to expectation, some dihydric and trihydric phenols, diamides and imides, which do not dissolve in CCl3CH3, had no effect of RE.In this paper, we tried to dissolve these insoluble organic reagents in CCl3CH3 by adding a solvent, and then examined whether these organic reagents had a large RE or not. The results are summarized as follows: 1) polyphenols (1, 3-dihydroxybenzene and 1, 3, 5-trihydroxybenzene and 1, 2, 3-trihydroxybenzene), diamides (succinic acid diamide and phthalic acid diamide) and imides (succinimide and phthalimide) could be dissolved in CCl3CH3 by using ethyl alcohol or acetone as a solvent. The RE of these organic reagents was found to be extremely large. 2) when two species of soluble organic reagents having different functional group were added in CCl3CH3, the RE was larger than that of one species, but smaller than that of other species. The synergistic action, that is, the phenomenon that the RE when two species of organic reagents were used simultaneously becomes larger than those of respective reagents, was not observed. Accordingly, when an insoluble organic reagent and a solvent were also added simultaneously, it is concluded that there was no synergistic action.

Peculiarities of the reaction of N,N?-substituted diphthalimides with amines

Macrocyclic phthalic acid diamides were obtained by the reaction of N,N′-substituted diphthalimides with polyoxyethylenediamines, while the corresponding tetraamides were obtained with primary aliphatic amines. It is shown that the reaction is a thermodynamically controlled process.

Reaction of Phthalic Thioanhydride with Aliphatic Amines

Phthalic thioanhydride (PTA) was allowed to react with aliphatic amines in ether at room temperature to give 1:2 adducts in good yields(Ta1e 1). Upon heating the 1:2 adduct above its fusion point, phthalic acid diamide was produced with evolution of hydrogen sulfide, The 1:2 adduct was decomposed by acid to produce PTA. ln the case of the reaction of PTA with aromatic amines, such an adduct was not formed. The reaction with aniline did not give an adduct but N-phenyl phthalimide.