KR0123414B1 - Novel abscisic acid derivatives with fluorine - Google Patents

Abstract

This invention relates to fluoride substituted abscisic acid derivatives of formula (I) wherein R is alkyl group of C1-C2, X is H2 or O, and Y is H or OH. A fluoride replaced abscisic acid derivative is produced by witting reaction of triethyl 2-fluorophosphonoacetate with alpha-ionone. Fluoride replaced abscisic acid (ABA) derivatives are more stable than natural ABA and have strong physiological activity, so they can be used as a active ingredient of plant growth regulators such as herbicides or dwarfing chemicals.

Description

Novel fluorine-substituted absic acid derivatives and preparation method thereof

The present invention relates to a novel fluorine-substituted absic acid derivative. More specifically, the present invention relates to novel fluorine-substituted absic acid derivatives represented by the following general formulas (I) and (II), methods for their preparation and use as plant growth regulators.

Wherein X is H ₂ or O; Y is H or OH; And R is H or an alkyl group having 1 to 2 carbon atoms.

Abscisic acid (ABA) is a type of plant hormone having the following structural formula, and unlike other plant hormones, it exhibits a physiological effect of inhibiting plant growth. In addition, since the concentration of abscisic acid is increased in various stressed plants, it is known that the compound has a high possibility of being used as an antistress agent for various textiles.

Numerous studies have been accumulated about the structure and activity of the absic acid derivatives, and the structure required for the active expression is also known. According to this, it can be summarized that the methyl group of C-3, C-2 'is important for activity expression, and the double bond of the side chain should have the structure of 2-cis-4-trans.

Unlike other plant hormones that have been industrially used, abscisic acid has not yet been put to practical use, although it exhibits significant physiological activity. To date, numerous absic acid derivatives have been synthesized, but still have activity of increasing abscitic acid. No compound is found. The reason for this is as follows: First, natural abscisic acid is unstable, and the side chain double bond isomerized easily by light to inactivate the structure of 2-trans-4-trans; Second, the concentration necessary for expressing the activity easily metabolized in the plant is not maintained.

On the other hand, various attempts have been made to overcome some of the above problems by modifying some of the structures of absic acid: Japanese Patent Laid-Open No. H3-2102, European Publication, for compounds related to the assis acid derivatives of the present invention; Patent EP 87,638 and European Patent EP 77,439 and the like. However, they did not contain a fluorine-substituent and were found to be significantly lower than abscinic acid in terms of physiological activity. Derivatives in which the side chain moiety of absciic acid are modified are known from Japanese Patent Application Laid-open No. Hei 1-254638, Japanese Patent Application Laid-open No. Hei 5-97844 and the like. However, they also did not contain a fluorine-substituent and were found to be remarkably lower in comparison with absic acid in terms of physiological activity.

Accordingly, the inventors of the present invention have found that 2-fluoroabbisic acid in which hydrogen at the C-2 position of abscisic acid is replaced with fluorine requires more energy than assis acid to isomerize from 2-cis to 2-trans. Compared to the fact that 2-fluoroabsic acid is not only more stable but also long-term expression with increased physiological activity, the results of intensive studies have shown that the novel fluorine-substituted abscides derivatives can The present invention has been accomplished by finding a method that can be synthesized using a process and can be easily produced in large quantities.

As a result, the first object of the present invention is to provide a fluorine-substituted absic acid derivative represented by the general formulas (I) and (II).

A second object of the present invention is to provide a method for producing an fluoric acid-substituted acetic acid derivative represented by the general formulas (I) and (II).

A third object of the present invention is to provide a use as a plant growth regulator comprising a fluorine-substituted absic acid derivative represented by the general formulas (I) and (II).

Although the fluorine-substituted absic acid derivatives of the present invention can be prepared through various reaction pathways, the following describes a representative-reaction pathway among them.

In the present invention, the fluorine-substituted absic acid derivatives represented by the general formulas (I) and (II) are trimethyl 2-fluorophosphonoacetate represented by the following structural formula (III) and α represented by the following general formula (IV). Prepared by a series of reactions involving the reaction of α-ionone derivatives. At this time, triethyl 2-fluorophosphonoacetate represented by the following structural formula (III) used as a starting material in the present invention is used for the construction of a fluorine-substituted vinyl group and usefully used to introduce fluorine into the side chain of absciic acid. Can be obtained in high yield by reacting triethyl phosphite with ethyl 2-bromo-2-fluoroacetate as a compound, α-nonone derivative represented by the general formula (IV) As intermediates useful for the preparation, they can be obtained by oxidation of? -Nonon or? -Nonon.

Wherein X is H ₂ or O; Y is H or OH.

Derivatives of the present invention can be prepared through the following process, but these methods do not limit the preparation method of the present invention.

[Step 1: Preparation of Triethyl 2-Fluorophosphonoacetate]

Triethyl 2-fluorophosphoacetate represented by the above general formula (III) can be obtained by reacting ethyl 2-bromo-2-fluoroacetate with triethyl phosphite. At this time, as the solvent, a solvent which does not adversely affect the reaction of benzene, toluene, xylene and the like may be used alone or in combination of two or more thereof. Although reaction temperature is not specifically limited, The temperature of the boiling point range of a solvent is suitable, and reaction time is preferable 20 hours.

Representing the first step in the reaction scheme is as follows:

First step:

[Second Step: Manufacturing Step of α-Yonon Derivative]

The α-nonon derivative represented by the general formula (IV) may be prepared by the following method:

The α-nonon derivative represented by the following structural formula (IV-a) can be obtained by directly oxidizing the α-nonon represented by the following structural formula (IV-d). In this case, as the solvent, a solvent which does not adversely affect the reaction such as alcohol, pyridine, carbon dichloride and carbon tetrachloride may be used alone or in combination of two or more thereof. Although reaction temperature is not specifically limited, The temperature in the boiling point range of a solvent is preferable from normal temperature, and the reaction time of 2 to 20 hours is preferable. As the oxidizing agent, t-butyl chromate, chromic acid, Jones reagent, pyridine chlorochromate and the like can be used.

The α-nonon derivative represented by the following structural formula (IV-b) can be obtained by epoxidizing β-nonon and then ring-opening. At this time, as the oxidizing agent used in the epoxidation reaction, hydrogen peroxide, acetic acid peroxide, benzoic acid peroxide and metachlorobenzoic acid peroxide may be used, and as a solvent, a solvent which does not adversely affect the reaction such as carbon tetrachloride, carbon trichloride, and carbon dichloride may be used alone. Or it can mix and use 2 or more types. The reaction temperature is not particularly limited. The temperature within the boiling point range of the solvent is preferably from -78 ° C, and the reaction time is preferably 2 to 20 hours. Sodium hydroxide, phenyl lithium and diethylamine lithium can be used as the base used for the ring-opening reaction, and a solvent which does not adversely affect the reaction such as carbon tetrachloride, carbon trichloride, carbon dichloride and tetrahydrocarbon can be used as the solvent. have. The reaction temperature is not particularly limited. The temperature within the boiling point range of the solvent is preferred from normal temperature, and the reaction time is preferably 2 to 20 hours.

In addition, the alpha-onon derivative represented by the following structural formula (IV-c) can be obtained by oxidizing α-nonon (IV-d).

In this case, as the solvent, a solvent which does not adversely affect the reaction such as alcohol, pyridine, carbon dichloride and carbon tetrachloride may be used alone or in combination of two or more thereof. The reaction temperature is not particularly limited, but a temperature within a boiling point range of the solvent from normal temperature is suitable, and the reaction time is preferably 2 to 20 hours. As the oxidizing agent, t-butyl chromate, chromic acid, Jones reagent, pyridine chlorochromate and the like can be used.

Representing the second step in the reaction scheme is as follows:

Second Step:

[Step 3: Preparation of Fluorine-Substituted Absic Acid Derivatives]

Fluorine-substituted absic acid derivatives represented by formulas (I) and (II) can be prepared by the following method:

The first method is applied to the case of producing a derivative in which R is an ethyl group in the fluorine-substituted absic acid derivatives represented by the general formulas (I) and (II). These derivatives can be obtained by the Wittich reaction of the α-yonone derivative represented by the general formula (IV) and triethyl 2-fluorophosphonoacetate represented by the general formula (III). In this case, as the base, sodium hydride (NaH), potassium hydride, sodium amidated, etc. may be used, and as the solvent, one or two or more solvents that do not adversely affect the reactions such as tenerahydrofuran and benzene It can be mixed and used. The reaction temperature is not particularly limited, but a temperature within the boiling point range of the solvent is preferable, and the reaction time is preferably 2 to 20 hours. The 2-cis-4-trans derivative (I-1) and 2-trans-4-trans derivative (II-1) obtained as a result of the reaction can be easily separated by chromatography or the like. Separated isomers were used.

The second method is applied to the case of producing a derivative in which R is H in the fluorine-substituted absic acid derivatives represented by the general formulas (I) and (II). These derivatives can be obtained by hydrolyzing ester compounds of 2-cis-4-trans derivative (I-1) and 2-trans-4-trans derivative (II-1) prepared in the first method. In this case, sodium hydroxide, potassium hydroxide, sodium methoxide and sodium ethoxide may be used as the base, and as the solvent, a solvent which does not adversely affect the reaction such as water and alcohol may be used alone or in combination of two or more thereof. . Although reaction temperature is not specifically limited, The temperature in the boiling point range of a solvent is preferable from normal temperature, and the reaction time of 2 to 20 hours is preferable.

The third method is applied to the case of producing a derivative in which R is a methyl group in the fluorine-substituted absic acid derivatives represented by the general formulas (I) and (II). These derivatives can be obtained by esterifying the derivatives (I-2) and (II-2) prepared in the second method. In this case, as the base, sodium hydroxide, potassium hydroxide, sodium methoxide and sodium ethoxide may be mixed and used, and as the solvent, a solvent which does not adversely affect the reaction, such as alcohol, may be used alone or in a mixture of two or more thereof. . Although reaction temperature is not specifically limited, The temperature in the boiling point range of a solvent is preferable from normal temperature, and the reaction time of 2 to 20 hours is preferable.

It is also possible to use a method of reacting with diazomethine in ether instead of the above method.

Representing the third step in the reaction scheme is as follows:

Third Process: (1) Method 1

(2) Second method

(3) Third method

Wherein X and Y are as defined above.

[Step 4: Preparation of Abbic Acid Derivative with Optical Activity]

Of the fluorine-substituted asisic acid derivatives represented by the above general formula, X is O, Y is OH, and R is H. The derivative has optical activity. Absic acid derivatives having such optical activity are derivatives obtained through the third method of the third step, wherein X is O, Y is OH, and R is a methyl group using a column capable of separating optical isomers. It can be separated by chromatography using HPLC or the like, and then obtained by hydrolysis.

The fourth step is represented by the following reaction scheme:

4th process:

The fluorine-substituted abscides derivatives represented by the general formulas (I) and (II) obtained in each step in the above production method are conventional in the art, such as distillation, crystallization, chromatography, etc., depending on the physical properties of each compound. The mixture is separated and purified according to the method used, and identification of the compound is performed using ¹ H-NMR and a mass spectrometer.

Through the present invention, the fluorine-substituted abscides derivatives represented by the following general formulas (I) and (II) can be used as active ingredients of pesticides and plant growth regulators having herbicidal activity by themselves, It is also useful as an intermediate to synthesize.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not limited to these examples according to the gist of the present invention.

Synthesis Example 1

Synthesis of Triethyl-2-fluorophosphonoacetate (First Step)

25 g (0.135 mmol) of ethyl 2-bromo-2-fluoroacetate and 67 g (0.4 mmol) of triethyl phosphite were mixed and heated to reflux for 4 hours, and then the reaction solution was distilled off and the residue was removed. Vacuum distillation was carried out under the conditions of a temperature of 126 DEG C and a vacuum degree of 3 mmHg to obtain 17 g of an oily substance (yield: 52 g).

¹ H-NMR (CDCl ₃ , TMS) δ: 1.39 (t, 9H), 4.29 (q, 6H), 5.2 (dd, 1H, J = 12 Hz, J = 36 Hz).

Synthesis Example 2

Synthesis of α-yonon Derivatives (Second Step)

Synthesis Example 2-1

Of 4- (1'-hydroxy-4'-oxo-2 ', 6', 6'-trimethyl-2'-cyclohexene-1'-yl) -3-buten-2-one (IV-a) synthesis

25 g (0.13 mmol) of α-ionone was dissolved in 100 ml of t-butyl alcohol, and 265 ml of t-butyl chromate solution (0.75 mmol solution) was slowly added dropwise for 20 hours while refluxing the reaction solution. After the reaction solution was heated to reflux for 5 hours, 500 ml of water was added, 100 ml of methyl alcohol and 20 g of oxalic acid were added to remove excess t-butyl chromate. The mixture was extracted using 2 L of chloroform, and the organic layer was dried over anhydrous magnesium sulfate. Evaporation under reduced pressure. The residue was purified by column chromatography (eluent: n-hexane: ethyl acetate = 5: 1 to 2: 1, v / v) to give 4.33 g of product. (Yield: 15%).

¹ H-NMR (CDCl ₃ , TMS) δ: 1.02 (s, 3H), 1.11 (s, 3H), 1.88 (d, 3H, J = 1.4Hz), 2.30 (s, 3H), 2.31 (bs, 1H , OH), 2.33 (d, 1HJ = 17.2Hz), 2.51 (d, 1HJ = 17.3Hz), 5.95 (s, 1H), 6.46 (d, 1H, J = 15.7Hz), 6.84 (d, 1H, J = 15.7 Hz).

Synthesis Example 2-2

Synthesis of 4- (1'-hydroxy 2 ', 6', 6'-trimethyl-2'-cyclohexene-1'-yl) -3-buten-2-one (IV-6)

Synthesis Example 2-2-1

Synthesis of 4- (1 ', 2'-epoxy-2', 6 ', 6'-trimethylcyclohexene-1'-yl) -3-buten-2-one (IV-6)

9.62 g (0.05 mmol) of β-nonone was dissolved in 100 ml of dried dichloromethane, and the reaction solution was cooled to 0 ° C., followed by addition of 17.26 g (50%, 0.05 mmol) of metachlorobenzoic acid peroxide. The reaction solution was stirred at room temperature for 20 hours, filtered, and the organic layer was washed with saturated aqueous sodium bicarbonate solution and 5% aqueous sodium sulfite solution, and then dried over anhydrous magnesium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography (eluent: n-hexane: acetylacetate-1: 4, v / v) to obtain 8.84 g of the product (yield: 85%).

¹ H-NMR (CDCl ₃ , TMS) δ: 0.93 (s, 3H), 1.14 (s, 6H), 1.38-1.95 (m, 6H), 2.28 (s, 3H), 6.28 (d, 1H, J = 15.7 Hz), 7.02 (d, 1H, J = 15.7 Hz).

MS m / e (rel. Int.): 208 (M +, 5), 193 (13), 135 (100), 123 (100), 107 (51), 95 (52), 79 (25), 69 ( 30), 43 (100).

Synthesis Example 2-2-2

Synthesis of 4- (1'-hydroxy 2 ', 6', 6'-trimethyl-2'-cyclohexene-1'-yl) -3-buten-2-one (IV-b)

100 ml of dried ether and 4.39 g (0.06 mmol) of diethylamine were mixed while passing through a nitrogen stream, and the reaction solution was cooled to -78 ° C. 25 ml (0.0625 mmol) of butyllithium (n-BuLi) solution (2.5 mmol) was slowly added dropwise to the reaction solution, and gradually warmed to −20 ° C., and then cooled to −78 ° C. again to obtain 4- (1). 4.16 g (0.02 mmol) of '2'-epoxy-2', 6 ', 6'-trimethylcyclohexane-1'-yl) -3-buten-2-one was dissolved in 10 ml of ether and slowly added to the reaction solution. . The reaction solution was stirred at room temperature for 12 hours, and then water was added and the organic layer was extracted with ether (3 × 50 ml) and dried over anhydrous magnesium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography (eluent: n-hexane: ethyl acetate = 1: 2, v / v) to obtain 0.957 g of a product (yield: 23%).

¹ H-NMR (CDCl ₃ , TMS) δ: 0.91 (s, 3H), 1.01 (s, 3H), 1.45-1.68 (m, 2H), 1.59 (s, 3H), 2.00-2.15 (m, 3H) , 2.29 (s, 3H), 5.56 (bs, 1H), 6.35 (d, 1H), 6.81 (d, 1H).

MS m / s (rel. Int.): 208 (M ⁺ , 4), 193 (9), 181 (5), 165 (21), 152 (11), 123 (20), 109 (100), 81 (22), 43 (39).

Synthesis Example 2-3

Synthesis of 4- (4'-oxo-2 ', 6', 6'-trimethyl-2'-cyclohexene-1'-yl) -3-buten-2-one (IV-c)

Jones reagent prepared by mixing α-ionon 1.5g (7.8 mmol) with 40 mol of acetone and adding 2 g (0.013 mmol) of chromic acid and 3 ml of concentrated sulfuric acid to 10 ml of 90% acetone aqueous solution was added to the reaction solution, followed by stirring at room temperature for 10 hours. I was. The reaction solution was filtered and the solvent was removed by evaporation under reduced pressure. The residue was purified by column chromatography (eluent: n-hexane: ethyl acetate = 1: 2, v / v) to obtain 0.45 g of a product (yield: 28). %)

¹ H-NMR (CDCl ₃ , TMS) δ: 1.01 (s, 3H), 1.08 (s, 3H), 1.90 (d, 3H, J = 1 Hz), 2.29 (s, 3H), 2.15-2.41 (m, 2H), 2.72 (d, 1H, J = 9.5 Hz), 5.98 (s, 1 Hz), 6.68 (dd, 1H, J = 15.8 Hz, 9.5 Hz).

MS m / e (rel. Int.): 206 (M ⁺ , 2), 191 (2), 164 (2), 150 (44), 135 (6), 108 (100), 43 (100).

Example 1

Preparation of 2-fluoroabic acid ethyl ester (I-1a) and (II-1a) (3rd process 1st method)

While passing through a nitrogen stream, 1.33 g (5.5 mmol) of triethyl 2-fluorophosphonoacetate prepared in Synthesis Example 1 was dissolved in 100 ml of dried tetrahydro tube, followed by 150 mg (5 mmol, 80% dispersion in mineral) of sodium hydride. oil) was added and stirred for 1 hour. 4- (1'-hydroxy-4'-oxo-2 ', 6', 6'-trimethyl-2'-cyclohexene-1'-yl) -3 prepared in Synthesis Example 2-1 to the reaction solution -10 g (5 mmol) of butene-2-one (IV-a) was added and heated to reflux for 12 hours. The reaction solution was cooled to room temperature, washed with water, extracted with ether, and the organic layer was dried over anhydrous magnesium sulfate. The residue obtained was purified by column chromatography (eluent: n-hexane: ethyl acetate = 4: 1, v / v). Purification and separation of the two geometrical isomers obtained in this Example yielded 0.62 g of Compound (I-1a) having an Rf value of 0.45 and 0.63 g of Compound (II-1a) having an Rf value of 0.38, respectively (yield: 80% ).

(2E, 4E) Isomers (I-1a):

Melting Point: 120-122 ° C

(2Z, 4E) Isomers (II-1a)

Melting Point: 114-115 ° C

[Examples 2 to 4]

Examples 2 to 4 were carried out except that α-nonon derivatives (IV-b) (IV-c) and (IV-d) were used instead of the α-nonon derivative (IV-a) used in Example 1. It carried out in the same manner as in Example 1. The chemical analysis results of the compounds prepared in Examples 1 to 4 are shown in Table 1 below.

Example 5

Examples 2 to 4 except that α-nonon derivatives (IV-b), (IV-c) and (IV-d) were used instead of the α-nonon derivative (IV-α) used in Example 1, It was carried out in the same manner as in Example 1. The chemical analysis results of the compounds prepared in Examples 1 to 4 are shown in Table 1 below.

Example 5

Preparation of (±) (2E, 4E) -2-fluoroabbic acid (I-2a) (third step second method)

0.2 g (0.645 mmol) of (±) (2E, 4E) -2-fluoroabbic acid ethyl ester (I-1a) prepared in Example I was dissolved in 5 ml of methyl alcohol, followed by 0.41 g of potassium hydroxide 5 ml of water. Dissolved in the reaction solution and heated to reflux for 1 hour. The methyl alcohol was removed by evaporation under reduced pressure, acidified with 2N hydrochloric acid solution, and purified by 20 ml of ethyl acetate with chuhexane: ethyl acetate: formic acid = 50: 50: 0.2, v / v) to give 0.132 g of product. The analytical results are shown in Table 1 below (yield: 72.6%).

Melting Point: 166 to 168 ° C

Example 6

Preparation of (±) (2Z, 4E) -2-fluoroabbic acid (II-2a)

The same method as in Example 5, except that 0.2 g (0.645 mmol) of (±) (2Z, 4E) -2-fluoroabbic acid ethyl ester (II-1a) prepared in Example 1 was used as a raw material. The product was obtained using (yield 71%).

Melting Point: 158-160 ° C

[Examples 7 to 9]

Examples 7 to 9 were carried out except that the compounds prepared in Examples 2 to 4 were used as raw materials instead of (±) (2E, 4E) -2-fluoroabbic acid ethyl ester (I-1a). It carried out in the same manner as in Example 5. The chemical analysis results of the compounds prepared in Examples 6 to 9 are shown in Table 1 below.

Example 10

Preparation of (±) (2E, 4E) -2-fluoroabdic acid methyl ester (I-3a) (third step third method)

10 ml of diazomethane (0.02 mmol solution) solution was added to the reaction solution to which 50 mg (0.177 mmol) of (±) (2E, 4E) -2-fluoroabbic acid (I-2a) prepared in Example 5 was added to 15 ml of ether. It was added and stirred for 20 minutes at room temperature. The residue obtained by evaporation of the reaction solution under reduced pressure was purified by column chromatography (eluent: n-hexane: ethyl acetate = 2: 1, v / v) to give 45 mg of product (yield: 86%).

Melting Point: 136-138 ° C

Example 11

Preparation of (±) (2Z, 4E) -2-fluoroabbic acid methyl ester (II-3a) (third step third method)

47 mg of the product was obtained in the same manner as in Example 10, except that 50 mg (0.17 mmol) of (2Z, 4E) -2-fluoroabbic acid (II-2a) prepared in Example 6 was used as a raw material. Obtained (yield: 89%). The chemical analysis results of the compounds prepared in Examples 10 to 11 are shown in Table 1 below.

Melting Point: 135-136 ° C

Example 12

Preparation of Abbic Acid Derivatives with Optical Activity (4th Step)

(±) (2E, 4E) -2-fluoroabbic acid methyl ester (I-3a) prepared in Example 10 was separated under optical conditions using HPLC under (S)-(+ ) -2-fluoroabic acid methyl ester and (R)-(+)-2-fluoroabic acid methyl ester were respectively fractionated. Each of the optical isomers fractionated was hydrolyzed in the same manner as in Example 5 to give (S)-(+)-2-fluoroabbic acid (I-4a) and (R)-(-)-2-fluoro Abbic acid (I-4b) was prepared, and optical activity and chemical analysis results are shown in Table 1 below.

Column: Chiral Cel OD (Daicel Chemical Ind., Japen) (4.6x250 mm)

Separation conditions: Solution: 3% IPA in hexane

Dissolution rate: 1 ml / min

Sample concentration: 10 mg / ml

Detection condition: UV 254nm

[Physical Activity of Plant Growth Regulators Containing Fluorine-Substituted Absic Acid Derivatives]

In the present invention, the plant growth regulator includes agents that exhibit various plant growth control actions such as germination inhibition, growth inhibition, plant growth inhibition such as herbicides and anti-dock action of plants such as dwarfing agents.

The plant growth regulator of the present invention can be used by a method of spraying a fluorine-substituted absic acid derivative in the form of an aqueous solution or the like on the ground planted with plants or plant seeds. In particular, in the case of herbicides among plant growth regulators, the fluorine-substituted absic acid derivative of the present invention can be added to the conventional herbicide component. Moreover, also in the case of a distortion agent, the fluorine-substituted abdic acid derivative of this invention can be added and used for the conventional distortion agent component. In addition, the fluorine-substituted absic acid derivative of the present invention can be used in combination with conventional plant fungicides and insecticides.

Hereinafter, a plant, a treatment site, a treatment time, a treatment method, a dosage amount, and a formulation of the plant growth regulator comprising the fluorine-substituted absic acid derivative of the present invention will be described in detail.

Iii) Plant to be applied: When the plant growth regulator of the present invention is used as a herbicide, the plant to be applied is all herb species, and when used as a dwarfing agent, an annual plant is preferable.

Ii) Treatment part: As the treatment part of the plant growth regulator of the present invention, the seed and foliage part of the plant are preferable.

Iii) Treatment time: The treatment time of the plant growth regulator of the present invention is the same as the treatment time of a conventional herbicide when used as a herbicide, and when used as a dwarfing agent, a planting period, a seedling period or a maturation period is preferable.

I) Treatment method: The treatment method of the plant growth regulator of the present invention is ground spraying when used as a herbicide, and ground spraying or soil mixing treatment is preferable when used as a dwarfing agent.

I) Treatment amount: When the plant growth regulator of the present invention is used as a herbicide, it is preferable to use an active ingredient of 0.01 mg or more per 1 m 2 of land, and when used as a dwarfing agent, 0.01 to 1 mg of active ingredient per 1 m 2 of land. Preference is given to using.

Iii) Formulation: The plant growth regulator of the present invention can be used in formulations such as hydrating agent, emulsion and powder by the conventional method for producing pesticides.

The germination inhibitory activity, α-amylase-induced inhibitory activity, and growth inhibitory activity of the derivatives having a configuration of (2E, 4E) among the fluorine-substituted absic acid derivatives synthesized by the preparation method of the present invention were reduced to The following method was used to compare with the cis acid:

1. Germination inhibition activity test

Ethyl alcohol was added to the absic acid derivative of the present invention to prepare a test solution. The test solution was then uniformly absorbed by a predetermined amount in a petri dish (6 cm inside diameter), and then air dried to remove the solvent. Distilled water was added to a separate Petri dish 1 ml each, and 25 seeds of cress (cress: Lepidium sativum) were uniformly flocculated, covered with a lid, and incubated at 25 ° C. under dark conditions. Then, after 36 hours, the number of non-germinated seeds was counted and calculated as a percentage of the germination rate of the control to obtain 50% germination inhibition rate (pi50) for each compound, and the test was repeated three times. At this time, the concentration of the fluorine-substituted absic acid derivative was 0.3 to 1 ppm.

2.α-Amirase Inhibition Activity Test

The barium (Hordeum vulgare L. var. Hexastichon) was sterilized, cut in half, and 10 endosperms were placed in sterile 2 ml of medium (containing 1 mM acetate buffer, pH 5.1, 20 μM calcium chloride), and then the absic acid derivative of the present invention. The test solution prepared from the above was added. For control, gibberlic acid (GA: gibberelic acid) was incubated at 25, for 48 hours, then barley half-seeds were changed with a homogenizer and washed with a buffer solution (3 ml) used for incubation. The supernatant was collected by centrifugation at 2000g for 10 minutes. The precipitate was added to 3 ml of the medium, and again mixed with the supernatant obtained by centrifugation. Distilled water was added to 10 ml of the supernatant obtained twice, and 10 ml was used as a sample liquid containing α-amylase. At this time, the concentration of the fluorine-substituted absic acid derivative was 0.3 to 1 ppm.

The enzyme solution obtained through the above procedure was measured for activity using the following α-amylase assay, and the activity was evaluated relative to the natural abstic acid: 100 mg of starch was dissolved in 10 ml of distilled water and used as a substrate. In order to stop and color the enzymatic reaction with α-amylase, 0.05% iodine (I2) solution containing 0.05N hydrochloric acid solution was used, wherein the iodine solution contains 1% urethra containing 10% iodine and potassium. Distilled water was added to 0.5 ml of the solution and 2.5 ml of 2N hydrochloric acid to prepare 100 ml. When measuring enzyme activity, 0.5 ml of substrate and 0.5 ml of 0.1 M acetate buffer (pH 5.1, 20 mM calcium chloride) were added to 10 ml of test tubes A and B (base solution), followed by enzymatic reaction for 5 minutes in a thermostat maintained at 30 ° C. Let. Then, 5 minutes later, 1 ml of the enzyme solution was added to Test Tube A to stop the reaction, and simultaneously cooled. Distilled water was added to measure absorbances (OD) D and D of the reaction solution and the substrate solution at 620 nm. The same method was applied to the sample solution containing α-amylase induced by the test compound, and the absorbance D was measured, and the relative amount of α-amylase was measured on the calibration curve obtained based on D measured by changing the concentration of the enzyme solution. Obtained by

3. Kidney inhibition activity test

Rice seedlings were planted 10 times in a medium in a test pot, and then the absic acid derivative of the present invention was prepared as a solution at a predetermined concentration and ground sprayed. The test pot was sealed with vinyl and incubated for 10 days at 25 to 30 ° C. to prevent evaporation of water, and then the length of the grass length of one vinegar of rice seedlings was measured and compared with the large structure without spraying the drug. At this time, the use concentration of the fluorine-substituted abstic acid derivative was 1 to 3 ppm.

Among the fluorine-substituted absic acid derivatives synthesized by the above examples, the germination inhibitory activity, α-amylase-induced inhibitory activity, and renal inhibitory activity of the derivatives having a coordination of (2E, 4E) were naturally induced. The results compared with the case of Susan are shown in Tables 2 to 4 below. As shown in Tables 2 to 4 below, derivatives having a coordination of (2E, 4E) in the fluorine-substituted absic acid derivatives of the present invention showed a germination inhibitory activity comparable to that of natural abscisic acid and Compared with the one-tenth equivalent to α-amylase-induced inhibitory activity, and about one-tenth the kidney inhibitory activity. As described above, derivatives having a coordination of (2E, 4E) among the fluorine-substituted absic acid derivatives of the present invention are much more stable than absic acid, and have high germination inhibitory activity and α-amylase-induced inhibitory activity like natural absicylic acid. And it has been confirmed that it can be used as a plant growth regulator, such as herbicides and dwarfs because it has a renal inhibitory activity.

As described and demonstrated in detail above, the fluorine-substituted abscides derivatives prepared according to the present invention are more stable than natural abscides and exhibit potent abscisdic activity in terms of physiological activity, and thus have pesticides having herbicidal activity as such. And it can be used as an active ingredient of plant growth regulators such as dwarfs, it was found to be useful as an intermediate for synthesizing the active ingredient.

Claims (4)

A fluorine-substituted absic acid derivative represented by the following general formula (I). Wherein X is H ₂ or O; Y is H or OH; And R is H or an alkyl group having 1 to 2 carbon atoms. A fluorine-substituted absic acid derivative having an optical activity represented by the following structural formula. A fluorine-substituted absic acid derivative having an optical activity represented by the following structural formula. A plant growth regulator comprising a fluorine-substituted absic acid derivative represented by the following general formula (I) as an active ingredient. Wherein X, Y and R are as described in claim 1.