JPH0570388A - Acaricide - Google Patents

Abstract

PURPOSE:To obtain an acaricide suitable for house, etc., having high safety to human and animals, excellent acaricidal activity, comprising a specific compound. CONSTITUTION:The objective acaricide comprising a cadinol of the formula (R is H or lower acyl; A is single bond, double bond or epoxy ring) such as T-cadinol, alpha-cadinol, dihydro-T-cadinol or dihydro-alpha-cadinol as an active ingredient. The acaricide is used in the form of emulsion, powder, aerosol, etc., and the concentration of the active component in the agent is preferably 40-60wt.%. An application amount, for example, is 5-20g/m<2> based on used target such as building part. And also, an acylated derivative, a dihydro derivative and an epoxy derivative of cadinol is new.

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 casino derivative containing casinos as an active ingredient.

[0002]

2. Description of the Related Art Recently, mites living indoors have been attracting attention as a social problem. That is, in an apartment house that is hot and humid, it becomes an environmental condition suitable for the growth of dust mites such as mosquito dust mites, which causes abnormal occurrence of dust mites, and the large amount of dust mites dead bodies and their excrements (feces, etc.) It has attracted attention as a social problem because it causes bronchial asthma and allergic diseases. 80-90% of the causative antigens of childhood bronchial asthma are said to be particularly feces of leopard mite, and therefore removal of these mite-derived antigenic substances from the living environment, that is, extermination of mites is emphasized.

Synthetic organophosphorus agents are generally used as repellents for mites, but there are many problems in terms of safety when used at home, and mites highly safe for humans and animals. There is a demand for pesticides and control agents. On the other hand, it has been reported that α-casinol, which is one of the sesquiterpene alcohols, is effective as a termite control agent (Japanese Patent Laid-Open No. 64-22807) or a wood preservative (Japanese Patent Laid-Open No. 63-19203). However, the effect of α-casinols on mites has not been reported yet.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have noticed that tree components have been used as insect repellents for a long time, and measured the acaricidal activity of various tree extract components to determine the natural insect repellent components. The highest acaricidal activity was found in the essential oil component of Hinoki cypress, and the structural analysis of this component revealed that the components were sesquiterpene alcohols α-casino and T-casino. Became. Based on these findings, the present invention was completed by further synthesizing a casino derivative and conducting research on their acaricidal activity. Therefore, an object of the present invention is to provide an acaricide containing casinos as an active ingredient. Still another object of the present invention is to provide a new casino derivative.

[0005]

The present invention has the following formula [I]:

[Chemical 3] (In the formula, R represents a hydrogen atom or a lower acyl group,
A- represents a single bond, a double bond or an epoxy ring) and an acaricide containing a casino as an active ingredient; and the following formula [I ']

[Chemical 4] (In the formula, R ′ represents a hydrogen atom or a lower acyl group,
When R'is a hydrogen atom, -A'- represents a single bond or an epoxy ring, and when R'is a lower acyl group, -A'- represents a double bond).

In the casino of the 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. Be done. T-casinols and α-casinoles, which are one of the active ingredients of the formula [I], are compounds known as one kind of sesquiterpene alcohol and have the chemical structural formulas shown below.

[Chemical 5]

Among the casinos represented by the formula [I], T-casinols, α-casinols, and dihydro-T.
-Casinosal and dihydro-α-casinosal have strong acaricidal activity and are preferred as active ingredients. You can use only one type of casino as an active ingredient,
Further, two or more kinds may be mixed and used. These casinos 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 an oil agent. Alternatively, an aqueous solution, an oil agent, an emulsifier, a penetrant, a stabilizer,
It is also possible to add a propellant or the like and use it in the form of an emulsion, a powder, an aerosol or the like.

The concentration of the active ingredient and the application rate of the active ingredient in the preparation may vary depending on the application method, the type of the active ingredient, the type of target mites, etc., but the concentration of the active ingredient is usually
It is 10 to 100% by weight, preferably 40 to 60% by weight. The applied amount is usually 1 to 100 g / m ² , and preferably 5 to 20 g / m for an application target such as a building site.
m ² . The acaricide of the present invention can be applied by applying, spraying, or spraying on a building site, bedding, clothing, etc., which is a target for controlling mites.

Among the casinos represented by the formula [I], T-casinols and α-casinoles are hexane-soluble obtained by further extracting a methanol extract of cypress with hexane, benzene, ethyl acetate and methanol in this order. The fraction can be obtained in high purity by subjecting it to silica gel column chromatography and then high performance liquid chromatography (HPLC). T-Casino and α-
The compound of formula [I '] which is a derivative of casinoyl can be synthesized as follows. An acylated derivative of T-casinoal or α-casinoline (a compound in which R'represents a lower acyl group and -A'-represents a double bond in the formula [I ']) is T-casinoal or α.
It can be obtained by reacting caffeine with an acid anhydride or an acid halide in the presence of pyridine. A dihydro derivative of T-casino or α-casino (in the formula [I '], R'represents a hydrogen atom,
Compounds in which -A'- represents a single bond) can be obtained by catalytic reduction of T-casinols or α-casinols in the presence of a palladium / carbon catalyst. Epoxy derivative of T-casinols or α-casinoles (a compound in the formula [I '] in which R'represents a hydrogen atom and -A'- represents an epoxy ring)
Can be obtained by reacting T-casinols or α-casinols with a peracid such as m-chloroperbenzoic acid. Each of the above reactions is a known reaction per se, and detailed reaction conditions and the like can be easily determined by those skilled in the art.

[0010]

The effects of the present invention are α-casino, T-casino, and derivatives thereof, dihydro-α-casino.
Casinols such as dihydro-T-casinoal have a strong acaricidal activity, and are particularly effective against dust mites such as mosquitoes. Therefore, the acaricide of the present invention containing caffeine as an active ingredient is extremely significant as an anthelmintic agent for mites that generate causative antigens for childhood asthma and allergic diseases.

[0011]

EXAMPLES The present invention will now be described in more detail with reference to examples. Example 1 Isolation and Purification of α-Casino and T-Casinos A wood chip obtained by crushing a cypress wood core material with a chipper was immersed in methanol for 3 days at room temperature and concentrated with an evaporator to obtain a cypress / methanol extract. The cypress-methanol extract (50 g) was extracted with hexane, benzene, ethyl acetate, and ethanol in this order, and the hexane-soluble fraction was subjected to silica gel column chromatography (Fuji-De).
Separation using Vison BW-350) gave two fractions 11, 12 eluting with hexane: ethyl acetate = 10: 1. These two fractions were respectively subjected to HPLC (Shim-pacPREP-SIL).
Was used to obtain α-casinols (500 mg) and T-casinoles (500 mg).

These purified components are α-casino and T
-The structure of being casino is determined as follows. According to GC-MS analysis, the molecular weight was 212 (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 shown in Table 1 below.

[Table 1]

From the ¹ H-NMR data in Table 1, it was revealed that it has one double bond, two terminal methyl groups and an isopropyl group. Furthermore, ¹ H, ¹³ C-N
As a result of finely examining the MR chemical shift, it was 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-Casino and Acetyl-α-Casino
111 mg of synthetic T-casino and α-casino each
(1 mmol) was dissolved in 5 ml of anhydrous methylene chloride, and 791 g (10 mmol) of anhydrous pyridine, 122 mg (1 mmol) of dimethylaminopyridine, 1.02 g (10 mmol) of acetic anhydride.
Was added and the mixture was 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, saturated aqueous sodium hydrogen carbonate solution and saturated brine in that order, and the extract was dried over anhydrous sodium sulfate. The extract was concentrated and then purified by silica gel column chromatography. Thus, acetyl-
70 mg T-Casino and 7 Acetyl-α-Casino
0 mg was obtained. ¹ H-NMR Acetyl-T-Casinoal: 2.10 ppm, acetyl group —CH ₃ , s, 3H Acetyl-α-Casinoyl: 2.15 ppm, acetyl group —CH ₃ , s, 3H.

Dihydro-T-casino and dihydro-
Synthesis of α-casinoal 111 mg each of T-casino and α-casino
(1 mmol) is dissolved in 5 ml of ethanol and the activity is 10% P
d / C was added and the reaction was carried out in a hydrogen stream for 12 hours. After the reaction was completed, Pd / C was filtered, concentrated and purified by silica gel column chromatography. Thus, dihydro-T-
110 mg of casino and 11 of dihydro-α-casino
0 mg was obtained. ¹ H-NMR dihydro-T-casinoal: 5.55 ppm disappeared; 1.0
And 0.9 ppm between -CH _{3 of the} iso-propyl group;
0.88 ppm, 11-position of -CH _3, d, 3H dihydro -α- Kajinoru: 5.56Ppm loss; 0.9
0ppm, 11th-CH ₃ , d, 3H epoxy-T-casino and epoxy-α-casino
111 mg of synthetic T-casino and α-casino each
(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 saturated aqueous sodium hydrogen carbonate solution and saturated brine in that order, and the extract was dried over anhydrous sodium sulfate. The extract was concentrated and then purified by silica gel column chromatography. Thus, 100 mg of epoxy-T-casino and 100 mg of epoxy-α-casino are obtained. ¹ H-NMR Epoxy-T-Casinoal: 5.55 ppm lost; 1.2
5 ppm, —CH ₃ , d, 3H at 11-position; 3.0 ppm, —H, d, 1H bonded to epoxy ring Epoxy-α-casinoal: 5.56 ppm disappeared; 1.3
ppm, —CH ₃ , d, 3H at position 11; 3.1 ppm, —H, d, 1H bonded to epoxy ring

Example 3 Acaricidal activity test of casinoles Mite A powder feed for breeding experimental animals adjusted to a water content of 15% (CE-250%, CLEA Japan, yeast extract 50%) was used as a breeding medium at a temperature of 25. Tests were carried on a mite mite, which was being bred in successive generations in an environment (in a desiccator) at a temperature of 75 ° C. and a relative humidity of 75% (adjusted with saturated saline). The acaricidal activity test method was performed according to the measurement method of Takaoka et al. Filter paper with a diameter of 14 mm (Toyo No. 5) was impregnated with casino oils (diluted with methanol) at a constant concentration (16 μg / cm ² ), and mosquito leopard mite (20-30
Hen) with the food. The filter paper has a diameter of 12 mm in the center to prevent dust mites from escaping from the filter paper.
It was sandwiched between two acrylic plates with holes of mm, a slide glass was placed on the top, and these three were fixed with clips. Put the acrylic plate incubating this scalloped mite into a petri dish with a diameter of 9 cm,
The sample was placed in a dark place at a temperature of 25 ° C. and a relative humidity of 75% (adjusted with saturated saline solution). The number of living mites 24 hours after the start of the experiment was examined under a stereoscopic microscope. 3 tests per sample
A test was conducted, and this test was repeated again at a later date, and a value obtained by averaging test data for a total of 6 times was determined according to the following formula. Mortality of insects (%) = (A / B) × 100 A = Number of ticks immediately after the start of the test B = Number of live ticks after each time The obtained results were as follows. Rate of casino mortality (%) α-casinole 87 T-casinoles 94 dihydro-α-casinoles 83 dihydro-T-casinoles 84 acetyl-α-casinoles 32 acetyl-T-casinoles 29 epoxy-α-casinoles 29 epoxy-T- Casino 32 ─────────────────────────────

Claims (4)

[Claims] 1. The following formula [I]: (In the formula, R represents a hydrogen atom or a lower acyl group,
A- is an acaricide containing a casino, which is represented by a single bond, a double bond or an epoxy ring) as an active ingredient. 2. The acaricide according to claim 1, which comprises T-casino, α-casino, dihydro-T-casino or dihydro-α-casino as an active ingredient. 3. The acaricide according to claim 1 or 2, which is effective against the mosquito mosquito. 4. The following formula [I ′]: (In the formula, R ′ represents a hydrogen atom or a lower acyl group,
When R'is a hydrogen atom, -A'- represents a single bond or an epoxy ring, and when R'is a lower acyl group, -A'- represents a double bond.