Pefurazoate is a 14α-demethylation inhibitor of 24-methylenedihydrolanosterol (24-MDL) and has an asymmetric carbon atom in its structure. We previously reported that the antifungal activity of the (S)-(-)-isomer of pefurazoate against Gibberella fujikuroi was about thirty times that of the (R)-(+)-isomer. This enantioselective antifungal activity was presumed to be due to an asymmetric molecular shape caused by the binding of a bulky 2-furanylmethyl group to a nitrogen atom adjacent to the asymmetric carbon atom. Therefore, to further elucidate the difference in antifungal activity between the two enantiomers of pefurazoate, we synthesized optically active N-methyl analogues of pefurazoate, and evaluated their antifungal activity. Optical (R)-(+)- and (S)-(-)-isomers of pefurazoate exhibited different activities against Cochliobolus miyabeanus and Pyricularia oryzae as well as Gibberella fujikuroi, but the N-methyl (R)-(+)- and (S)-(-)-isomers of the pefurazoate analogues had almost the same degree of activity against these three fungi and of inhibition of ergosterol biosynthesis in G. fujikuroi. These findings strongly suggest that the enantioselective antifungal activity of pefurazoate is due to its asymmetric molecular shape caused by substitution of the furan ring.

View full abstract

The interaction of 2, 4-dichlorophenoxyacetic acid (2, 4-D) with multi-lamellar vesicles of dimyristoyl and dipalmitoyl L-α-phosphatidylcholine was examined from the pH dependency of partition and pH-and temperature-dependent polarization of fluorescence probes such as 1, 6-Biphenyl-1, 3, 5-hexatriene. It was strongly suggested that 2, 4-D in the undissociated form was located at the region from the neighborhood of the glycerol backbone to a shallow site of the hydrophobic core of the lipid bilayers and that its anionic species was adsorbed at the membrane surface. Fluorescence study with the derivatives of 2, 4-D showed that hydrophobicity and pKa of these acids determined their interaction with membrane.

View full abstract

Synthesis of the diastereomers of (+)-altholactone, an antitumor acetogenin from various Goniothalamus species, was achieved. Four isomers including 3a, 7a-trans-fused analogs were synthesized from 2, 3-O-cyclohexylidene-D-glyceraldehyde via twice separation of diastereomers.

View full abstract

Both enantiomers of altholactone, Isoaltholactone and 5-hydroxygoniothalamin were synthesized from tri-O-acetyl-D-glucal, and biological activities of altholactones were examined. For brine shrimp, the configuration of 3-hydroxy group at convex site was important for lethal activity, while (2S, 3S)-configuration was inhibitory to lettuce germination.

View full abstract

Efficacy of acetamiprid tablet against the cotton aphid on cucumber by various soil application methods was investigated compared to that of its granule applied under the same conditions. Acetamiprid tablet weighed 0.15g including 20mg active ingredient at 1 tablet/plant and controlled-release 2% granule at the dosage of 1g/plant showed excellent efficacy when they were applied at the center of planting hole, similarly to the granule applied uniformly. The comparison between the efficacy in row application of tablet and soil surface application of granule suggested the efficacy of both applications became insufficient as the distance between the foot of seedling and application site became longer. Such a tendency was more remarkable with row application of the tablet than with soil surface application of granule. The tablet exhibited excellent efficacy at the dosage of 1 tablet/plant by being applied both at the foot of plant in nursery pot before transplanting to the field and at the center of the planting hole. Besides, efficacy of different sizes of tablet including same amount of acetamiprid was investigated by planting hole application. There was a tendency that tablet exhibited longer lasting activity as it became larger as far as the weight of 0.15, 0.3 and 0.6g. With soil surface application the tendency of efficacy was reversed compared to that with planting hole application.

View full abstract

Degradation of imazosulfuron in upland soils was investigated under laboratory conditions using two kinds of ¹⁴C labeled imazosulfuron. Imazosulfuron degraded with half-life of approximately 40 days, and the major degradation pathway was the hydrolysis of the sulfonylurea bond to give ADPM and IPSN. The leaching studies of imazosulfuron using non-aged and aged soils were also conducted. It was found that imazosulfuron was less mobile in soils when the soil column was eluted with 0.02N CaCl₂ solution after 30 days of aging period of time compared to non-aging. Main degradation products, ADPM and IPSN, were adsorbed in soils stronger than imazosulfuron. It was suggested that imazosulfuron dissipates relatively fast in upland soils, and the leaching potential decreases with time.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

Safety evaluation of Acequinocyl was conducted via comprehensive studies. Acute toxicity is very low in every exposure route for both Acequinocyl and the 15% SC formulation. Primary irritation potential of Acequinocyl 15% SC formulation is minimal for eyes and nil for skin. Acequinocyl 15% SC formulation has no skin sensitization potential. In long term studies, hemorrhagic changes and/or prolonged blood clotting time were observed in rats treated with high doses of Acequinocyl. Similar changes were also observed in pharmacology studies in which rats dosed with a single high dose of Acequinocyl showed increased fibrinogen level and prolonged blood clotting time. As Acequinocyl has a chemical structure similar to that of vitamin K, it is assumed that Acequinocyl competes against vitamin K in the mechanism of blood coagulation in rats. No effect on reproductive ability was observed in rats. In teratogenicity studies, no teratogenic effect was observed even in the highest doses that induced embryotoxic changes. No mutagenic effect was observed in genetic toxicity studies, and no specific non-neoplastic/neoplastic lesions were observed in chronic studies. ADI value for Acequinocyl was established at 0.027mg/kg/day based on the NOAEL in the 80-Week Carcinogenicity Study In Mice. Maximum residue levels on crops established by the Japanese Ministry of Health and Welfare are 1ppm for eggplants, 0.5ppm for cucumbers and gherkins, 0.1ppm for watermelons and melons, 0.2ppm for mandarin oranges, 2ppm for natsudaidai, 1ppm for lemons and other citrus fruits than mandarin oranges and natsudaidai, 1ppm for apples, 2ppm for pears and Japanese pears, 0.1ppm for peaches, 1ppm for plums and prunes, 2ppm for cherries and 0.5ppm for grapes. Acequinocyl 15% SC formulation is considered to be a useful agent in the agricultural field on account of its excellent acaricidal effect and minimal risk to humans and the environment when used in accordance with the instructions.

View full abstract