JP4934293B2 - Plant vitality composition - Google Patents

Description

  The present invention relates to a 5-aminolevulinic acid ester sulfonic acid salt useful in the fields of microorganisms / fermentation, animals / medicine, plants, and the like, a production method thereof, a medical composition containing the same, and a plant vital agent composition containing the same About.

  The hydrochloride of 5-aminolevulinic acid ester is a cancer treatment (Non-patent Document 1) in the medical field, a herbicide (Patent Document 1), a salt tolerance improver (Patent Document 2), and a seed treatment agent in the plant field. (Patent Document 3) is known to be useful.

  On the other hand, the production method of 5-aminolevulinic acid esters is known only as a hydrochloride, for example, a method of condensing 5-aminolevulinic acid hydrochloride and alcohol in the presence of a condensing agent (Patent Document 1), 5-alkoxycarboxamide. A method for removing an amino-protecting group of levulinic acid ester (Patent Document 1, Non-Patent Document 2) has been reported.

On the other hand, when 5-aminolevulinic acid ester hydrochloride is administered to an animal or plant or a cell thereof, a sterilization operation may be required in advance. For example, radiation irradiation described in JP-T-2001-514243 may be used. The sterilization method by was known.
However, the method by radiation irradiation requires a special device. As a simple sterilization method, there is a heat sterilization method, but 5-aminolevulinic acid ester hydrochloride has a property of low melting point (low heat resistance). Therefore, the sterilization method by heating involves a solid phase change. The application of the superheat sterilization method was difficult.
Jean-Michel Gaullier et.al., Cancer Research, 57, 1481-1486 (1997) H. Brunner et.al., Photochemistry and Photobiology, 78 (5), 481-486 (2003) Japanese Patent Laid-Open No. 4-9360 JP-A-8-151304 Japanese Patent Laid-Open No. 2001-10

  Therefore, this invention is providing the novel salt of 5-aminolevulinic acid ester excellent in heat resistance, its manufacturing method, the medical composition containing this, and a plant vital agent composition.

  As a result of intensive studies in view of such circumstances, the inventors of the present invention can obtain a specific 5-aminolevulinic acid ester sulfonic acid salt satisfying the above requirements by acting a 5-aminolevulinic acid sulfonic acid salt and an alcohol. As a result, the present invention has been completed.

That is, the present invention provides the following general formula (1)
R ¹ OCOCH ₂ CH ₂ COCH ₂ NH ₂ · HOSO ₂ R ² (1)
Wherein, R ¹ is hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, shows amino, aryl, oxo, fluoro, chloro and hydrocarbon radicals groups selected from nitro which may be substituted; R ² is Hydroxy or R ¹ is indicated. R ¹ and R ² may be the same or different.
The 5-aminolevulinic acid ester sulfonic acid salt represented by these is provided.

Further, the present invention provides the following general formula (2)
HOCOCH ₂ CH ₂ COCH ₂ NH ₂ and HOSO ₂ R ² (2)
[R ² is as defined above]
5-aminolevulinic acid sulfonate represented by the following general formula (3)
R ¹ OH (3)
[R ¹ is as defined above]
A method for producing a 5-aminolevulinic acid ester sulfonic acid salt represented by the above general formula (1), which comprises condensing an alcohol represented by formula (1).

  Furthermore, the present invention provides a photodynamic therapeutic or diagnostic composition containing the 5-aminolevulinic acid ester sulfonic acid salt represented by the general formula (1). The present invention further provides a plant vitality composition containing a 5-aminolevulinic acid ester sulfonic acid salt represented by the general formula (1).

  The 5-aminolevulinic acid ester sulfonic acid salts of the present invention have a decomposition temperature higher than that of the hydrochloride, so that the heat sterilization operation is simple. Moreover, according to the manufacturing method of this invention, 5-aminolevulinic acid ester sulfonic acid salts can be manufactured simply and efficiently.

In the general formula (1), R ¹ represents a hydrocarbon group which may be substituted with a group selected from hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo, fluoro, chloro and nitro. Here, the hydrocarbon group is preferably an alkyl group, an alkenyl group, an aralkyl group or an aryl group. Here, as an alkyl group, a linear, branched or cyclic alkyl group is mentioned, A C1-C40, Furthermore, a 1-18, especially 1-7 alkyl group is preferable. Examples of the alkenyl group include linear, branched or cyclic alkenyl groups, and alkenyl groups having 2 to 40 carbon atoms and more preferably 2 to 18 carbon atoms are preferable. Examples of the aralkyl group include those composed of an aryl group having 6 to 20 carbon atoms and an alkyl group having 1 to 6 carbon atoms. Moreover, as an aryl group, a C6-C20 aryl group is mentioned.

As an alkoxy group, a C1-C18 alkoxy group, especially a C1-C7 alkoxy group are preferable. The acyloxy group is preferably an alkanoyloxy group having 1 to 18 carbon atoms, particularly an alkanoyloxy group having 2 to 8 carbon atoms. As the alkoxycarbonyloxy group, a C _1-18 alkoxy-carbonyloxy group, particularly a C _1-7 alkoxy-carbonyloxy group is preferable.

  Preferred examples of the alkyl group having 1 to 18 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, and neopentyl group. Tert-pentyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, ethylbutyl group, n-heptyl group, 2-methylhexyl group, n-octyl group, isooctyl group, tert-octyl group Group, 2-ethylhexyl group, 3-methylheptyl group, n-nonyl group, isononyl group, 1-methyloctyl group, ethylheptyl group, n-decyl group, 1-methylnonyl group, n-undecyl group, 1,1- Dimethylnonyl group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n-pentadecyl group, - hexadecyl group, n- heptadecyl group, n- octadecyl group.

  More preferable examples of the alkyl group having 1 to 7 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, and neopentyl. Group, tert-pentyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, ethylbutyl group, n-heptyl group and 2-methylhexyl group.

When the fluoro is substituted, the number of fluoro may be in the range of 1 to 37, and the position to be substituted is not limited, but preferably-(CH ₂ ) _M (CF ₂ ) _N R ³ [M 0 to 6 and N represents an integer of 1 to 7. However, the sum of M and N is 1-7. R ³ represents hydrogen or fluoro. ], For example, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl, 4,4,4- Trifluorobutyl, 3,3,4,4,4-pentafluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, 5,5,5-trifluoropentyl, 4,4,5 , 5,5-pentafluoropentyl, 2,2,3,3,4,4,5,5-octafluoropentyl, 3,3,4,4,5,5,5-hexafluoropentyl, 3,3 4,4,5,5,5-heptafluoropentyl, 2,2,3,3,4,4,5,5,5-nonafluoropentyl, 6,6,6-trifluorohexyl, 5,5 , 6,6,6-pentafluorohexyl, 4,4,5,5,6,6,6-heptafluorohexyl, 3,3, , 4,5,5,6,6,6-nonafluorohexyl, 2,2,3,3,4,4,5,5,6,6,6-undecafluorohexyl, 7,7,7- Trifluoroheptyl, 6,6,7,7,7-pentafluoroheptyl, 5,5,6,6,7,7,7-heptafluoroheptyl, 4,4,5,5,6,6,7, 7,7-nonafluoroheptyl, 3,3,4,4,5,5,6,6,7,7,7-undecafluoroheptyl, 2,2,3,3,4,4,5,5 , 6,6,7,7,7-tridecafluoroheptyl and the like, particularly preferably 2,2,3,3,4,4,4-heptafluorobutyl, 2,2,3,3, and the like. 4,4,5,5-octafluoropentyl, 3,3,4,4,5,5,6,6,6-nonafluorohexyl, 2,2,3,3,4,4,5,5 6, 6, Is a 7,7-bird decafluoro heptyl.

  Examples of the alkyl group having 1 to 18 carbon atoms substituted by hydroxy include 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl and the like.

Examples of the C1- _C18 alkyl group substituted by alkoxy include C _1-7 alkoxy-C _1-18 alkyl groups such as 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 4 -Methoxybutyl, 4-ethoxybutyl, 2- (2-methoxyethyl) ethyl and the like.

Examples of the alkyl group substituted with an acyloxy group include a C _2-7 alkanoyloxy-C _1-18 alkyl group. Examples of the alkyl group substituted by an alkoxycarbonyloxy group include a C _1-18 alkoxy-carbonyloxy-C _1-18 alkyl group. Examples of the alkyl group substituted with an amino group include an amino-C _1-18 alkyl group.
Examples of the alkenyl group having 2 to 18 carbon atoms include vinyl group, allyl group, isopropenyl group, 2-butenyl group, 2-methylallyl group, 1,1-dimethylallyl group, 3-methyl-2-butenyl group, 3- Methyl-3-butenyl group, 4-pentenyl group, hexenyl group, octenyl group, nonenyl group, decenyl group, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, cyclooctenyl group, 4-methylcyclohexenyl Group, 4-ethylcyclohexenyl group, 2-cyclopentenylethyl group, cyclohexenylmethyl group, cycloheptenylmethyl group, 2-cyclobutenylethyl group, 2-cyclooctenylethyl group, 3- (4-methylcyclo Hexenyl) propyl group, 4-cyclopropenylbutyl group, 5- (4 Ethylcyclohexenyl) pentyl group, oleyl group, bacenyl group, linoleyl group, linolenyl group, trans-9-octadecenyl group, 9E, 12E-octadecadienyl group, 9E, 12E, 15E-octadecatrienyl group, etc. It is done.

The aralkyl group having 7 to 26 carbon atoms is preferably one composed of an alkyl group having 1 to 6 carbon atoms and an aryl group having 6 to 20 carbon atoms. Examples of the alkyl group having 1 to 6 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, n-hexyl group, A cyclopropyl group, a cyclobutyl group, a cyclohexyl group, etc. are mentioned, As a C6-C20 aryl group, a phenyl group, a naphthyl group, etc. are mentioned. Of the aralkyl groups having 7 to 26 carbon atoms, a benzyl group, a phenethyl group, and a 9-fluorenylmethyl group are preferable, and a benzyl group and a fluorenylmethyl group are particularly preferable. The aryl group of the aralkyl group has 1 to 6 carbon atoms such as the above-described alkyl group having 1 to 6 carbon atoms, methoxy group, ethoxy group, n-propoxy group, n-butoxy group, isobutoxy group, tert-butoxy group and the like. May be substituted by 1 to 3 substituents such as a carboxy group or a halogen atom such as an alkoxy group, a hydroxyl group, an amino group, a nitro group, a cyano group, fluorine, chlorine, bromine or iodine. As such a substituted aralkyl group, —CH ₂ C ₆ H ₄ F _p R ⁴ (R ⁴ is selected from hydrogen, fluoro, chloro, methyl, ethyl, propyl, butyl, trifluoromethyl, nitro and methoxy. And p represents an integer of 0 to 4), particularly 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 4-methoxybenzyl, 4-trifluoromethylbenzyl, 4-chlorobenzyl, 3,4-dichlorobenzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-nitrobenzyl, 4-nitrobenzyl, 2,3,4,5-tetrafluorobenzyl, 2 , 3,4,5,6-pentafluorobenzyl is preferred.

  Examples of the aryl group having 6 to 20 carbon atoms include a phenyl group and a naphthyl group. For example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, C1-C6 alkyl group such as n-pentyl group, n-hexyl group, cyclopropyl group, cyclobutyl group, cyclohexyl group, methoxy group, ethoxy group, n-propoxy group, n-butoxy group, isobutoxy group, tert -Substituted by 1 to 3 substituents such as a C1-C6 alkoxy group such as a butoxy group, a hydroxyl group, an amino group, a nitro group, a cyano group, a halogen atom such as fluorine, chlorine, bromine or iodine, or a carboxy group It may be.

R ² in the general formula (1) is hydroxy or a group represented by R ¹ . Examples of R ² include all the groups described for R ¹ above. Among these, as R < ² >, a C1-C18 alkyl group, an aralkyl group, or an aryl group is preferable. Examples of the alkyl group having 1 to 18 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 2-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, ethylbutyl group, n-heptyl group, 2-methylhexyl group, n-octyl group, isooctyl group, tert-octyl group 2-ethylhexyl group, 3-methylheptyl group, n-nonyl group, isononyl group, 1-methyloctyl group, ethylheptyl group, n-decyl group, 1-methylnonyl group, n-undecyl group, 1,1-dimethyl Nonyl group, n-dodecyl group, n-tridecyl group, n-tetradecyl group, n-pentadecyl group, n-hex A decyl group, n-heptadecyl group, n-octadecyl group, etc. are mentioned, Preferably it is a C1-C16 alkyl group, More preferably, a methyl group, an ethyl group, n-propyl group, isopropyl group, n- Examples thereof include a butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, n-hexadecyl group, and 2-ethylhexyl group. The aralkyl group is preferably a benzyl group, and the aryl group is preferably a phenyl group.

  The 5-aminolevulinic acid ester sulfonic acid salt of the present invention represented by the general formula (1) may be solid or liquid. The solid indicates a crystalline state, a glass state, or a liquid crystal state, and may be a hydrate. The liquid refers to a melted state or solution. The solution means a state in which it is dissolved or dispersed in a solvent such as water, but the pH may be adjusted with a pH adjuster or the like. In addition, two or more kinds of solvents including water may be mixed and used. pH adjusters include phosphoric acid, boric acid, phthalic acid, citric acid, succinic acid, tris, acetic acid, lactic acid, tartaric acid, oxalic acid, phthalic acid, maleic acid and their salts. A buffer solution may be mentioned.

The 5-aminolevulinic acid ester sulfonic acid salt (1) of the present invention has the following general formula (2):
HOCOCH ₂ CH ₂ COCH ₂ NH ₂ and HOSO ₂ R ² (2)
[Wherein R ² is as defined above]
And a compound represented by the following general formula (3)
R ¹ OH (3)
[Wherein R ¹ is as defined above]
It is manufactured by condensing the compound represented by these. The reaction can be obtained by dissolving or dispersing compound (2) in compound (3) and stirring with heating.

  Further, instead of the compound (2), other salts of 5-aminolevulinic acid, such as hydrochloride, hydrobromide, hydroiodide, nitrate, borate, phthalate, citrate, succinate Acid salts, acetate salts, lactate salts, tartrate salts, oxalate salts, maleate salts and the like can also be used as raw materials. In this case, after completion of the reaction, sulfonic acids may be further reacted.

When the dissolved state or dispersed state is not desired, an appropriate solvent can be added for dilution.
Examples of the solvent include water, ketones (acetone, methyl ethyl ketone, etc.), esters (methyl acetate, ethyl acetate, propyl acetate, butyl acetate, γ-butyrolactone, etc.), ethers (diethyl ether, methyl tert-butyl ether, Ethyl tert-butyl ether, dimethoxyethane, tetrahydrofuran, dioxane and the like). Although there is no restriction | limiting in particular in the temperature in the case of heating, Preferably it is room temperature-100 degreeC.

  The reaction may be performed using a condensing agent. Such condensing agents include dicyclohexylcarbodiimide, diisopropylcarbodiimide, N-ethyl-N′-3-dimethylaminopropylcarbodiimide and its hydrochloride, benzotriazol-1-yl-tris (dimethylamino) phosphonium hexafluorophosphate salt And diphenylphosphoryl azide.

Furthermore, the general formula (5)
HOSO ₂ R ² (5)
(Wherein R ² is as defined above)
It is also possible to condense in the presence of sulfonic acids represented by Examples of such sulfonic acids include methyl sulfonic acid, ethyl sulfonic acid, n-propyl sulfonic acid, isopropyl sulfonic acid, n-butyl sulfonic acid, sec-butyl sulfonic acid, tert-butyl sulfonic acid, n-pentyl sulfone. Acid, isopentylsulfonic acid, neopentylsulfonic acid, tert-pentylsulfonic acid, 2-methylbutylsulfonic acid, n-hexylsulfonic acid, isohexylsulfonic acid, 3-methylpentylsulfonic acid, ethylbutylsulfonic acid, hexadecyl Sulfonic acid, 2-ethylhexylsulfonic acid, oleylsulfonic acid, benzylsulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfonic acid, 2,4-dimethylbenzenesulfonic acid, 2,5-dimethylbenzenesulfonic acid, 4-ethylbenzene Sulfonic acid, 4- (n-propyl) benzenesulfonic acid, 4-isopropylbenzenesulfonic acid, 4- (n-butyl) benzenesulfonic acid, 4- (sec-butyl) benzenesulfonic acid, 4- (tert-butyl) Benzenesulfonic acid, 4- (n-pentyl) benzenesulfonic acid, 4- (isopentyl) benzenesulfonic acid, 4- (neopentyl) benzenesulfonic acid, 4- (tert-pentyl) benzenesulfonic acid, 4- (2-methylbutyl ) Benzenesulfonic acid, 4- (n-hexyl) benzenesulfonic acid, 4-isohexylbenzenesulfonic acid, 4- (3-methylpentyl) benzenesulfonic acid, 4- (ethylbutyl) benzenesulfonic acid, 4- (hexadecyl) Benzenesulfonic acid, 4- (2-ethylhexyl) benzenesulfone , And 4-oleyl benzenesulfonic acid.

  When recovering the solid from the reaction solution, it is possible to add a poor solvent to the reaction solution. The poor solvent is not particularly limited as long as it is a solvent having a polarity lower than that of the reaction solvent, but is preferably selected from the above reaction solvents. When the solid recovery rate is low, the recovery rate can be improved by cooling.

  As shown in the examples below, 5-aminolevulinic acid ester sulfonic acid salts (1) have higher heat resistance and are difficult to decompose. Therefore, sterilization by heating is easy, and 5-aminolevulinic acid ester sulfonic acid salts are useful as photodynamic therapy or photodynamic diagnostic agents in animals including humans, like 5-aminolevulinic acid ester hydrochloride. Examples of the photodynamic therapy or diagnostic agent include those for cancer, infection, rheumatism, thrombus, acne and the like.

  When the 5-aminolevulinic acid ester sulfonic acid salt is used as a photodynamic therapeutic agent or diagnostic agent, it may be used under known conditions. Specifically, JP-T-2001-501970, JP-T 4- No. 500770, No. 2005-501050, No. 2004-506005, No. 2001-518498, No. 8-507755, No. 2004-505105, No. 11- What is necessary is just to use it by the prescription and method currently disclosed by 501914 gazette.

  The composition for photodynamic treatment or photodynamic diagnosis containing a 5-aminolevulinic acid ester sulfonic acid salt can be made into a dosage form such as an external preparation for skin, an injection, an oral preparation, or a suppository. In preparing these dosage forms, a pharmaceutically acceptable carrier can be used. As the carrier, water, a binder, a disintegrant, a dissolution accelerator, a lubricant, a filler, an excipient and the like are used.

Moreover, when using 5-aminolevulinic acid ester sulfonic acid salt for a plant use, you may contain the fertilizer component etc. which are generally used, for example. As a fertilizer component, the substance currently disclosed by Unexamined-Japanese-Patent No. 4-338305 is mentioned.
5-Aminolevulinic acid ester sulfonic acid salts are also useful as plant activators. When used as a plant activator, it may be used under known conditions. Specifically, it may be used for plants by the method disclosed in JP-A-7-53487.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Example 1 Preparation of 5-aminolevulinic acid methyl ester p-toluenesulfonate 50-4.7 mg (1.64 mmol) of 5-aminolevulinic acid p-toluenesulfonate and 1.9 mg (0.01 mmol) of p-toluenesulfonic acid monohydrate The mixture was added to 3 mL of methanol and stirred at 60 ° C. for 16 hours. After cooling the reaction solution, 40 mL of isopropanol was added and stirred for 30 minutes. The precipitated crystals were collected by filtration and dried under reduced pressure at room temperature to obtain 286.5 mg (0.903 mmol) of the desired product. Recovery 55 mol%.
¹ H-NMR (D ₂ O, 400 MHz) δ ppm: 2.38 (s, 3H, Aromatic-CH ₃ ), 2.68 (t, 2H, CH ₂ ), 2.87 (t, 2H, CH ₂ ), 3.67 (s , 3H, OCH ₃ ), 4.10 (s, 2H, CH ₂ ), 7.35 (d, 2H, Ar-H), 7.68 (d, 2H, Ar-H)
¹³ C-NMR (D ₂ O, 100 MHz) δ ppm: 23 (CH ₃ ), 30 (CH ₂ ), 37 (CH ₂ ), 50 (CH ₂ ), 55 (OCH ₃ ), 128 (Aromatic), 132 (Aromatic), 142 (Aromatic), 145 (Aromatic), 178 (COO), 207 (C = O)
Elemental analysis values: C ₆ H ₁₁ NO ₃ and C ₇ H ₈ SO ₃ Theoretical values: C 49.20%; H 6.03%; N 4.41%
Actual value: C 49.0%; H 5.9%; N 4.3%

Example 2 Preparation of 5-aminolevulinic acid hexyl ester p-toluenesulfonate 50-66 mg (1.64 mmol) of 5-aminolevulinic acid p-toluenesulfonate and 1.9 mg (0.01 mmol) of p-toluenesulfonic acid monohydrate In addition to 3 mL of n-hexanol, the mixture was stirred at 80 ° C. for 16 hours. After cooling the reaction solution, 20 mL of cyclohexane was added and stirred, and allowed to stand at 4 ° C. for 18 hours. The precipitated crystals were collected by filtration and dried under reduced pressure at room temperature to obtain 520.4 mg (1.34 mmol) of the desired product. Recovery rate 82 mol%.
¹ H-NMR (D ₂ O, 400 MHz) δ ppm: 0.85 (t, 3H, CH ₃ ), 1.28 (s, 6H, 3CH ₂ ), 1.59 (t, 2H, CH ₂ ), 2.37 (s, 3H , Aromatic-CH ₃ ), 2.65 (t, 2H, CH ₂ ), 2.86 (t, 2H, CH ₂ ), 4.07 (t, 4H, 2CH ₂ ), 7.34 (d, 2H, Aromatic-H), 7.67 ( d, 2H, Aromatic-H)
¹³ C-NMR (D ₂ O, 100 MHz) δ ppm: 16 (CH ₃ ), 23 (Aromatic-CH ₃ ), 25 (CH ₂ ), 28 (CH ₂ ), 30 (CH ₂ ), 31 (CH ₂ ), 34 (CH ₂ ), 37 (CH ₂ ), 50 (CH ₂ ), 69 (OCH ₂ ), 128 (Aromatic), 132 (Aromatic), 142 (Aromatic), 145 (Aromatic), 178 (COO ), 207 (C = O)
Elemental analysis value: C ₁₁ H ₂₁ NO ₃ · C ₇ H ₈ SO ₃ Theoretical value: C 55.79%; H 7.54%; N 3.61%
Found: C 55.1%; H 7.3%; N 3.6%

Example 3 Preparation of 5-aminolevulinic acid benzyl ester p-toluenesulfonate 5-aminolevulinic acid p-toluenesulfonate 502.8 mg (1.64 mmol) and p-toluenesulfonic acid monohydrate 1.9 mg (0.01 mmol) The mixture was added to 3 mL of benzyl alcohol and stirred at 80 ° C. for 16 hours. After cooling the reaction solution, 20 mL of cyclohexane was added and stirred, and allowed to stand at 4 ° C. for 18 hours. The precipitated crystals were collected by filtration and dried under reduced pressure at room temperature to obtain 494.5 mg (1.26 mmol) of the desired product. Recovery rate 77 mol%.
¹ H-NMR (D ₂ O, 400 MHz) δ ppm: 2.35 (s, 3H, CH ₃ ), 2.70 (t, 2H, CH ₂ ), 2.86 (t, 2H, CH ₂ ), 4.06 (s, 2H , CH ₂ ), 5.11 (s, 2H, OCH ₂ ), 7.32 (d, 2H, Aromatic-H), 7.38-7.42 (m, 5H, Aromatic-H), 7.67 (d, 2H, Aromatic-H)
¹³ C-NMR (D ₂ O, 100 MHz) δ ppm: 23 (CH ₃ ), 30 (CH ₂ ), 37 (CH ₂ ), 50 (CH ₂ ), 70 (OCH ₂ ), 128 (Aromatic), 131.2 (Aromatic), 131.6 (Aromatic), 131.7 (Aromatic), 132 (Aromatic), 138 (Aromatic), 142 (Aromatic), 145 (Aromatic), 177 (COO), 207 (C = O)
Elemental analysis value: C ₁₂ H ₁₅ NO ₃ · C ₇ H ₈ SO ₃ Theoretical value: C 58.00%; H 5.89%; N 3.56%
Actual value: C 57.2%; H 5.9%; N 3.4%

Example 4 Melting point measurement Melting point and decomposition point of various crystals of 5-aminolevulinic acid ester p-toluenesulfonate were measured using EXSTAR6000 thermal analysis system (TG / DTA) manufactured by Seiko Instruments Inc. The results are shown in the table. As a comparative example, the melting point of hydrochloride is also shown. As a result, when the hydrochloride was changed to p-toluenesulfonate, the heat resistance was improved.

Example 5 Plant vitality effect 600 g of field soil was filled in a magnetic pot having an inner diameter of 12 cm, 12 seeds of radish were sown, covered with 5 mm, and grown in a greenhouse. The foliage spraying treatment with the spray liquid described once a day was performed. The state of the leaves after 21 days was observed. The results are summarized in Table 2. As a result, 5-aminolevulinic acid ester sulfonate showed a plant vitality effect equivalent to 5-aminolevulinic acid sulfonate.

Claims (1)

The following general formula (1)
R ¹ OCOCH ₂ CH ₂ COCH ₂ NH ₂ · HOSO ₂ R ² (1)
[In the formula, R ¹ represents hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo, fluoro, chloro and hydrocarbon group which may group selected from nitro substituted by,; R ² is 4-methylphenyl group is shown . ]
The plant vitality agent composition containing 5-aminolevulinic acid ester p-toluenesulfonate represented by these .