JP2958169B2 - Acaricide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an acaricide and a casinole derivative containing casinoles as an active ingredient.

[0002]

2. Description of the Related Art In recent years, mites that live indoors have attracted attention as a social problem. That is, in an apartment house that is hot and humid, environmental conditions suitable for the growth of house dust mite, such as Dermatophagoides pteronyssinus, cause abnormal occurrence of house dust mites. It is a pathogen of bronchial asthma and allergic diseases and is attracting attention as a social problem. It is said that 80-90% of the antigens causing pediatric bronchial asthma are particularly feces of Dermatophagoides, and therefore, the removal of antigenic substances derived from these mites from the living environment, that is, extermination of mites, is regarded as important.

[0003] Synthetic organophosphorus agents are generally used as acaricides, but there are many problems in terms of safety when used at home, and mites that are highly safe for humans and animals. There is a need for pesticides and pesticides. On the other hand, it has been reported that α-casinol, one of the sesquiterpene alcohols, is effective as a termite control agent (Japanese Patent Application Laid-Open No. 22807/1988) or a wood preservative (Japanese Patent Application Laid-Open No. 63-19203). However, the effect of α-Casineur on mites has not yet been reported.

[0004]

SUMMARY OF THE INVENTION The present inventors have paid attention to the fact that tree components have been used as insect repellents since ancient times, measured the acaricidal activity of various tree extract components, and determined the natural insect repellent components. The search revealed that the essential oil component of hinoki cypress had the highest acaricidal activity. As a result of structural analysis of this component, it was found that this component was sesquiterpene alcohols α-casinole and T-casinole. Became. Based on such findings, a casinole derivative was further synthesized, and studies on their acaricidal activity were carried out to complete the present invention. Accordingly, an object of the present invention is to provide an acaricide containing casinoles as an active ingredient. Still another object of the present invention is to provide a novel casinole derivative.

[0005]

The present invention provides a compound represented by the following formula [I]:

Embedded image (Wherein, R represents a hydrogen atom or a lower acyl group;
A- represents a single bond, a double bond or an epoxy ring), a miticide containing as an active ingredient a casinols represented by the following formula [I ']:

Embedded image (Wherein R ′ represents a hydrogen atom or a lower acyl group;
-A'- represents a single bond or an epoxy ring when R 'is a hydrogen atom, and -A'- represents a double bond when R' is a lower acyl group.

In the casole of formula [I] used as an active ingredient in the present invention, examples of the lower acyl group of R include lower acyl groups having 2 to 6 carbon atoms such as acetyl, propanoyl, butanoyl, pentanoyl and hexanoyl. Can be T-Casinole and α-Casinole, one of the active ingredients of the formula [I], are compounds known as a kind of sesquiterpene alcohol and have the following chemical structural formulas.

Embedded image

Among the casinoles represented by the formula (I), T-casinole, α-casinole, dihydro-T
-Casinols and dihydro-α-casinols have strong acaricidal activity and are preferred as active ingredients. The casinoles as an active ingredient may be used alone,
Further, two or more kinds may be used in combination. These casinols may be used as they are without being mixed with other components, or may be diluted with water or a suitable organic solvent and used as an aqueous solution or oil. Alternatively, an emulsifier, a penetrant, a stabilizer, an aqueous solution, an oily agent,
A propellant or the like may be added to use as a form of an emulsion, a powder, an aerosol, or the like.

[0008] The concentration of the active ingredient in the preparation and the application rate of the active ingredient can vary depending on the application method, the kind of the active ingredient, the kind of the target mite, and the like.
It is 10 to 100% by weight, preferably 40 to 60% by weight. The application rate is, for example, 1 to 100 g / m ² , preferably 5 to 20 g /
m ² . The acaricide of the present invention can be applied by applying, spraying, spraying, or the like on a building site, bedding, clothing, or the like from which mites are to be eliminated.

Among the casinols represented by the formula [I], T-casinole and α-casinole are obtained by further extracting a methanol extract of cypress in the order of hexane, benzene, ethyl acetate, and methanol, and obtaining a hexane-soluble compound. The fractions can be obtained in high purity by further subjecting them to silica gel column chromatography followed by high performance liquid chromatography (HPLC). T-Casineur and α-
The compound of the formula [I '], which is a derivative of casinole, can be synthesized as follows. Acylated derivatives of T-casinol or α-casinole (compounds in which R ′ in the formula [I ′] represents a lower acyl group and —A′- represents a double bond) are T-casinol or α-casinol.
-It can be obtained by reacting casinols with acid anhydrides or acid halides in the presence of pyridine. A dihydro derivative of T-casinol or α-casinol (in the formula [I '], R' represents a hydrogen atom;
-A'- represents a single bond) can be obtained by catalytic reduction of T-casinole or α-casinole in the presence of a palladium / carbon catalyst. Epoxy derivatives of T-casinole or α-casinole (compounds where R ′ in the formula [I ′] represents a hydrogen atom and —A′- represents an epoxy ring)
Can be obtained by reacting T-casinol or α-casinol with a peracid such as m-chloroperbenzoic acid. Any of the above-mentioned reactions are per se known reactions, and detailed reaction conditions and the like can be easily determined by those skilled in the art.

[0010]

As described above, α-casinole and T-casinol, and dihydro-α-casinole which is a derivative thereof,
Casinoles such as dihydro-T-casinole have strong acaricidal activity and are particularly effective against dust mite such as Dermatophagoides pteronyssinus. Therefore, the acaricide of the present invention containing casinols as an active ingredient is extremely significant as an anthelmintic for mites that generates an antigen that causes pediatric bronchial asthma and allergic diseases.

[0011]

The present invention will be described in more detail with reference to the following examples. Example 1 Isolation and Purification of α-Casinol and T-Casinol A wood chip obtained by crushing the core of hinoki cypress wood with a chipper was immersed in methanol at room temperature for 3 days and concentrated by an evaporator to obtain a hinoki / methanol extract. The hinoki / methanol extract (50 g) was extracted in the order of hexane, benzene, ethyl acetate and ethanol, and the hexane-soluble fraction was subjected to silica gel column chromatography (Fuji-De).
Separation was performed using Vison BW-350) to obtain two fractions 11 and 12 eluted with hexane: ethyl acetate = 10: 1. Each of these two fractions was subjected to HPLC (Shim-pacPREP-SIL)
To obtain α-casinol (500 mg) and T-casinol (500 mg).

These purified components are α-Casinole and T
-The determination of the structure as being casinoles was made as follows. According to GC-MS analysis, the molecular weight was 212 (m / m
z), the active ingredients of the two fractions are C
It was suggested to be a ₁₅ O ₁ H ₂₆ sesquiterpene alcohol. For the two fractions 11 and 12
The results of ¹³ C-NMR and ¹ H-NMR are as shown in Table 1 below.

[Table 1]

From the ¹ H-NMR data shown in Table 1, it was found that the compound had one double bond, two terminal methyl groups and an isopropyl group. Further, ¹ H, ¹³ C-N
A close examination of the MR chemical shift revealed that one terminal methyl group was bonded to a double bond and the other was bonded to a carbon atom having a tertiary hydroxyl group. Further ¹ H- ¹ HCOSY, ¹³ compounds of fraction 12 by acquiring various secondary spectrum, such as C- ¹ HCOSY is α- Kajinoru, compounds of fraction 11 was found to be a T- Kajinoru.

Example 2 Acetyl-T-Casinols and Acetyl-α-Casinols
Synthetic T-Cainsil and α-Cainsil each 111 mg
(1 mmol) was dissolved in 5 ml of anhydrous methylene chloride, 791 g (10 mmol) of anhydrous pyridine, 122 mg (1 mmol) of dimethylaminopyridine, 1.02 g (10 mmol) of acetic anhydride.
Was added and stirred at room temperature for 24 hours. After completion of the reaction, 50 ml of methylene chloride was added, and the mixture was washed with 3N hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline in this order, and the extract was dried over anhydrous sodium sulfate. The extract was concentrated and purified by silica gel column chromatography. Thus, acetyl-
T-Casinol 70 mg and Acetyl-α-Casinol 7
0 mg was obtained. ¹ H-NMR acetyl -T- Kajinoru: 2.10ppm, -CH ₃ acetyl group, s, 3H acetyl -α- Kajinoru: 2.15ppm, -CH ₃ acetyl group, s, 3H

Dihydro-T-casinol and dihydro-
Synthetic of α-Cainsill 111 mg each of T-Cainsil and α-Cainsill
(1 mmol) was dissolved in 5 ml of ethanol and the activity was 10% P
d / C was added and reacted in a hydrogen stream for 12 hours. After completion of the reaction, Pd / C was filtered and concentrated, and then purified by silica gel column chromatography. Thus, dihydro-T-
110 mg of caisson and dihydro-α-casinol 11
0 mg was obtained. ¹ H-NMR dihydro-T-casinol: 5.55 ppm disappeared; 1.0
Between 0.9 and 0.9 ppm, -CH _{3 of the} iso-propyl group;
0.88 ppm, -CH ₃ , d, 3H at position 11 dihydro-α-casinal: 5.56 ppm disappeared; 0.9
0 ppm, -CH ₃ , d, 3H epoxy-T-casinole and epoxy-α-casino at position 11
Synthetic T-Cainsil and α-Cainsil each 111 mg
(1 mmol) was dissolved in 5 ml of anhydrous methylene chloride, 417 mg (3 mmol) of m-chlorobenzoic acid was added, and the mixture was reacted at room temperature for 24 hours. After completion of the reaction, 50 ml of methylene chloride was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline in this order, and the extract was dried over anhydrous sodium sulfate. The extract was concentrated and purified by silica gel column chromatography. Thus, 100 mg of epoxy-T-casinol and 100 mg of epoxy-α-casinol were obtained. ¹ H-NMR Epoxy-T-Casinole: 5.55 ppm disappeared; 1.2
5 ppm, -CH ₃ , d, 3H at position 11; 3.0 ppm, -H, d, 1H attached to the epoxy ring, epoxy-α-casinol: 5.56 ppm, disappearance; 1.3
ppm, 11-position of _{-CH 3, d, 3H; 3.1ppm} , -H bound to the epoxy ring, d, IH

Example 3 Acaricidal activity of mites killing test mite A powdered feed for raising laboratory animals (CE-250% manufactured by CLEA Japan, 50% yeast extract) adjusted to a water content of 15% was used as a breeding medium at a temperature of 25%. Under the environment (in a desiccator) of 75 ° C. and a relative humidity of 75% (adjusted with a saturated saline solution), a tester of the octopus mite, continuously reared, was used. Acaricidal activity The test was performed according to the measurement method of Takaoka et al. A filter paper having a diameter of 14 mm (Toyo No. 5) is impregnated with a certain concentration (16 μg / cm ² ) of casinoles (diluted with methanol), and Dermatophagoides pteronyssinus (20-30) is placed on the filter paper.
Were placed with their food. In order to prevent Dermatophagoides farinae from escaping from the filter paper, place the filter paper in the center at a diameter of 12
It was sandwiched between two acrylic plates having a hole of mm, and a slide glass was further placed on the upper part, and these three pieces were fixed with clips. Put the acrylic plate containing the house dust mite in a 9 cm diameter petri dish,
The sample was placed in a dark environment at a temperature of 25 ° C. and a relative humidity of 75% (adjusted with a saturated saline solution). The number of surviving mites 24 hours after the start of the experiment was examined under a stereoscopic microscope. Testing is 3 per sample
A test was conducted, and this test was repeated again at a later date. Mortality (%) = (A / B) × 100 A = mite number immediately after the start of test B = viable mite number after each time The obtained results were as follows. Caesar mortality (%) α-Casinol 87 T-Casinol 94 Dihydro-α-Casinol 83 Dihydro-T-Casinol 84 Acetyl-α-Casinol 32 Acetyl-T-Casinol 29 Epoxy-α-Casinol 29 Epoxy-T- Casino Le 32

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-1-193204 (JP, A) JP-A-1-163104 (JP, A) (58) Fields investigated (Int.Cl. ⁶ , DB name) A01N 31/06 A01N 37/08 A01N 43/20 A01N 65/00 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] [Claim 1] The following formula [I] (Wherein, R represents a hydrogen atom or a lower acyl group;
A- represents a single bond, a double bond, or an epoxy ring) as an active ingredient. 2. The acaricide according to claim 1, which contains T-casinol, α-casinol, dihydro-T-casinol or dihydro-α-casinol as an active ingredient. 3. The acaricide according to claim 1, which is effective against Dermatophagoides pteronyssinus.