JP5737751B2 - Shikimic acid acquisition method and shikimic acid production method - Google Patents

Description

  The present invention relates to a method for obtaining shikimic acid and a method for producing shikimic acid.

  Shikimic acid is an important intermediate in the reaction pathway for plants to biosynthesize aromatic compounds, and is contained in many plants. Shikimic acid is also used as a starting material for influenza drug Tamiflu (registered trademark). Shikimic acid isolated from star anise (also called “octagon”) is used in the manufacture of the influenza treatment drug Tamiflu.

  By the way, in recent years, studies on low melting point organic salts composed of only ions (referred to as “Ionic Liquid”) have been conducted. Some ionic liquids enter a liquid state near room temperature. In addition, the ionic liquid has high polarity as a result of being composed only of ions, and has characteristics such as non-volatility, high thermal stability, and chemical stability. Some ionic liquids can dissolve cellulose that is difficult to dissolve in common organic solvents and water. The ionic liquid is also referred to as “ionic liquid”. An ionic liquid that is in a liquid state near room temperature is also referred to as “room temperature molten salt” or “room temperature molten salt”.

  One of the researches on ionic liquids is an acquisition method that uses ionic liquids to acquire natural organic compounds that are soluble in ethyl acetate from ginkgo biloba leaves. In this conventional acquisition method, components contained in ginkgo leaves (also referred to as “ginkgo leaf components”) are extracted from ginkgo leaves using an ionic liquid capable of dissolving cellulose as a solvent. And in the conventional acquisition method, after adding ethyl acetate which is not compatible with an ionic liquid, an ethyl acetate layer is collect | recovered. And in the conventional acquisition method, the natural organic compound which melt | dissolves in ethyl acetate is acquired by removing the ethyl acetate of the collect | recovered ethyl acetate layer by distillation.

Yuta Ono Masahiro Fujita Makiko Sato Yutaka Usuki Hiroko Takeoka "Establishment of an efficient extraction method of natural organic compounds derived from Ginkgo biloba leaves by ionic liquid" Polymer Preprints, Japan, Polymer Society (2010) Vol. 59, No1 2Pa139

  However, the above-described conventional acquisition method merely acquires a natural organic compound that dissolves in ethyl acetate from ginkgo leaves, and cannot acquire shikimic acid that does not dissolve in ethyl acetate.

  Considering the shortage of star anise resources and the demand for the influenza drug Tamiflu, the conventional method for isolating shikimic acid from star anise described above has insufficient shikimic acid supply and a new method for obtaining shikimic acid. Is required.

  The disclosed technology has been made in view of the above, and an object thereof is to provide a new method for obtaining shikimic acid and a method for producing shikimic acid.

  The disclosed shikimic acid acquisition method includes, in one embodiment, an extraction step in which a plant is added to an ionic liquid capable of dissolving cellulose to perform extraction from the plant. Further, the shikimic acid acquisition method comprises mixing the extract obtained in the extraction step with a solvent that is compatible with the ionic liquid and can dissolve shikimic acid, and from the mixture of the extract and the solvent. A solid-liquid separation step of removing the insoluble matter by solid-liquid separation and collecting the separated liquid. Further, the shikimic acid acquisition method comprises contacting the separated liquid collected in the solid-liquid separation step with a strongly basic anion exchange resin, thereby converting the shikimic acid contained in the separated liquid to the strongly basic anion exchange. An adsorption process for adsorbing to resin is included. Moreover, the shikimic acid acquisition method is a method of washing the strongly basic anion exchange resin, to which shikimic acid has been adsorbed in the adsorption step, with deionized water, thereby remaining in the strongly basic anion exchange resin. A cleaning step of removing the ionic liquid; The shikimic acid obtaining method includes an obtaining step of obtaining the shikimic acid from the strongly basic anion exchange resin washed by the washing step.

  According to one aspect of the disclosed shikimic acid acquisition method, it is possible to provide a new shikimic acid acquisition method and shikimic acid production method.

FIG. 1 is a diagram showing an example of a chart obtained by reverse phase HPLC analysis. FIG. 2 is a diagram showing the extraction rate of shikimic acid from the green leaves of female ginkgo biloba.

  Hereinafter, the disclosed shikimic acid acquisition method and shikimic acid production method will be described in detail. The disclosed shikimic acid acquisition method and shikimic acid production method include an extraction step, a solid-liquid separation step, an adsorption step, a washing step, and an acquisition step. Moreover, the disclosed shikimic acid acquisition method and shikimic acid production method may further include a recovery step. Further, the disclosed method for obtaining a substance from an ionic liquid and the method for producing a substance from an ionic liquid include an adsorption step, a washing step, and an obtaining step.

(Shikimic acid acquisition method and shikimic acid production method)
As will be described in detail below, in the disclosed shikimic acid obtaining method and shikimic acid producing method, it is possible to obtain shikimic acid from a plant using a non-volatile ionic liquid as an extraction solvent. For example, shikimic acid can be obtained from abundant ginkgo leaves. Moreover, by using an ionic liquid as an extraction solvent, it is possible to provide a shikimic acid acquisition method and a shikimic acid production method that can repeatedly use the extraction solvent. Moreover, compared with the case where another organic solvent or water is used as an extraction solvent, it is possible to provide a shikimic acid acquisition method and a shikimic acid production method capable of efficiently acquiring shikimic acid.

  In the extraction step, the plant is added to an ionic liquid capable of dissolving cellulose to perform extraction from the plant. Here, as the ionic liquid in the extraction step, any ionic liquid may be used as long as it can dissolve cellulose, and it is preferable to use an ionic liquid having a thermal decomposition temperature higher than 180 ° C. which is the melting point of shikimic acid. An ionic liquid refers to a liquid which is fluid over a wide temperature range and is completely composed of ions. For example, the salt which will be in a liquid state below 100 degreeC or below room temperature is shown.

  The ionic liquid is a salt and has a cation and an anion. As the cation of the ionic liquid used in the extraction step, for example, organic cation such as quaternary ammonium cation, imidazolium cation and pyridinium cation may be used singly or in combination. For example, the cation of the ionic liquid is preferably a 1-butyl-3-methylimidazolium cation, a 1-ethyl-3-methylimidazolium cation, or a 1-allyl-3-methylimidazolium cation, more preferably 1-butyl-3-methylimidazolium cation, 1-ethyl-3-methylimidazolium cation.

Examples of the anion of the ionic liquid include BF ₄ ⁻ , PF ₆ ⁻ , AsF ₆ ⁻ , SbF ₆ ⁻ , AlCl ₄ ⁻ , HSO ₄ ⁻ , ClO ₄ ⁻ , CH ₃ SO ₃ ⁻ , and CH ₃ SO ₄ ^−. , CH ₃ C ₆ H ₄ SO ₃ ⁻ , CF ₃ SO ₃ ⁻ , CF ₃ SO ₄ ⁻ , CF ₃ CO ₂ ⁻ , C ₂ F ₅ CO ₂ ⁻ , (CF ₃ SO ₂ ) ₂ N ⁻ , (C _{2 ^{F 5 SO 2) 2 N -}} , phosphonic acid, phosphate ion ^{_{((CH 3 O) 2 PO}} 2 -, (CH 3 O) CH 3 PO 2 -, (CH 3 O) C 2 H 5 OPO 2 - , (CH ₃ O) HPO ₂ ⁻ , (C ₂ H ₅ O) ₂ PO ₂ ⁻ , (C ₂ H ₅ O) CH ₃ PO ₂ ⁻ , (C ₂ H ₅ O) C ₂ H ₅ PO ₂ ⁻ , _{(C 2 H 5 O) HPO} 2 -), halide ions, Carboxylate ion having 1 to 3 carbon atoms, formic acid ions (HCOO ^-), perchlorate ion, pseudohalide ions, Shianamidoion (NCN ^-), dicyanamide ion (N _{(CN) 2 ^-)} may be used such as . Halide ions include, for example, Cl ⁻ , Br ⁻ , I ⁻ and the like. The pseudohalide ions, for example, CN ^- and ^{SCN -, OCN -, ONC -} , N 3 - , and the like. For example, the anion of the ionic liquid is preferably Cl ⁻ , phosphate anion, or carboxylic acid anion, more preferably Cl ⁻ or methyl phosphite anion ((CH ₃ O) HPO ₂ ⁻ ), Acetic acid anion (CH ₃ COO ⁻ ).

  Examples of the combination of the cation and the anion of the ionic liquid include 1-butyl-3-methylimidazolium chloride (hereinafter referred to as “[bmim] Cl”) and 1-butyl-3-methylimidazolium acetic acid. 1-allyl-3-methylimidazolium chloride, 1-allyl-3-methylimidazolium methylphosphorous acid, 1-ethyl-3-methylimidazolium methylphosphorous acid, 1-ethyl-3-methylimidazolium diphosphate It is preferable to use cyanamide, 1-butyl-3-methylimidazolium dicyanamide, or the like. Moreover, as a combination of a cation and an anion of an ionic liquid, for example, [bmim] Cl, 1-allyl-3-methylimidazolium methyl phosphorous acid, 1-ethyl-3-methylimidazolium methyl phosphorous acid is used. Is more preferable. In addition, the commercially available ionic liquid may be used in the extraction step, or one synthesized by a known method may be used.

  As the plant in the extraction process, any plant may be used as long as it contains shikimic acid. Moreover, as a plant in an extraction process, arbitrary parts may be used among arbitrary plants containing shikimic acid, and all the plants may be used. As a part of a plant, for example, it is preferable to use a leaf of a plant, and it is more preferable to use a green leaf. Plants in the extraction process include, for example, ginkgo biloba leaves, binanka pod leaves, cypress leaves, eucalyptus leaves, senryo leaves, cypress leaves, sudajii leaves, shikimi leaves, binankazura leaves, bamboo rush leaves, genus Leaves, Mucous leaves, Sakaki leaves, Mokukoku leaves, Asebi leaves, Satsuki azalea leaves, Gardenia leaves, Hirohoshi no Kusa fusa leaves are preferred, female Ginkgo biloba green leaves, Binan quail green leaves, Tochinoki green leaves , Eucalyptus green leaf, green leaf of senryo, green leaf of cypress, green leaf of sudajii, green leaf of shikimi, green leaf of binankazura, green leaf of bamboo shoot, green leaf of genus mushroom, green leaf of green croaker, green leaf of oyster, green leaf of red fox Green leaves, gardenia green leaves, and green leaf Ri preferred.

  Moreover, as a plant in an extraction process, it is preferable to use the pulverized plant from a viewpoint of improving extraction efficiency, and it is more preferable to use a powdery thing. As a method for pulverizing plants, any method may be used, and it is preferable to pulverize after freezing. As a method for pulverizing the plant, for example, it is preferable to pulverize the plant after freezing it using a freezer, liquid nitrogen, dry ice or the like, and it is preferable to pulverize the plant after freezing the plant using liquid nitrogen. More preferred. As a method of pulverizing the frozen plant, any method may be used, and pulverization may be performed using a mortar.

  As a temperature for performing the extraction, any temperature may be used, and it is preferable to use a high temperature in a temperature range in which shikimic acid does not melt. As a temperature for performing extraction, for example, it is preferable to use 100 ° C to 200 ° C, more preferably 120 ° C to 170 ° C, and still more preferably 150 ° C to 170 ° C.

  Any time may be used as the extraction time. As a time for performing the extraction, for example, it is preferable to use 30 minutes to 10 hours, and it is more preferable to use 1 hour.

  Any weight ratio may be used as the weight ratio between the plant and the ionic liquid in the extraction step. The weight ratio between the plant and the ionic liquid is preferably, for example, that the weight of the ionic liquid is greater than 1 and less than 9 with respect to 1 part by weight of the plant, more preferably 2 to 6 parts by weight of the ionic liquid. The ionic liquid is more preferably 2 to 4 parts by weight. In addition, the value shown as an example of weight ratio shows ratio of the weight of the ground material which grind | pulverized the plant which was not dried, and the weight of an ionic liquid. Plants that have been dried may be used, or plants that have not been dried may be used.

  It supplements about weight ratio. Compared with common organic solvents such as methanol and ethanol, the viscosity of the ionic liquid is high. Based on this, the weight ratio of the plant to the ionic liquid is such that the weight part of the ionic liquid is larger than 1 and smaller than 9 with respect to 1 part by weight of the plant, so that the plant can be immersed in the ionic liquid easily It is possible to facilitate the stirring of the ionic liquid by adding the plant to the highly viscous ionic liquid.

  In the solid-liquid separation step, the extract obtained in the extraction step is mixed with a solvent that is compatible with the ionic liquid and can dissolve shikimic acid, and the insoluble matter is separated from the mixture of the extract and the solvent by solid-liquid separation. And the separated solution is recovered. That is, by mixing the extract obtained in the extraction step and the solvent, a mixed solution having a reduced viscosity as compared with the extract is generated once, and insoluble matters are removed from the generated mixed solution.

  In other words, instead of solid-liquid separation of an extract using an ionic liquid having a high viscosity, the ionic liquid is mixed with a solvent capable of dissolving shikimic acid by being compatible with the ionic liquid and then solid-liquid separated. Even when is used as a solvent, solid-liquid separation can be easily performed.

  Here, as a solvent mixed with the extract in the solid-liquid separation step, any solvent that is compatible with the ionic liquid and can dissolve shikimic acid may be used. As the solvent mixed with the extract in the solid-liquid separation step, for example, methanol, ethanol, water, dimethylformaldehyde, and dimethyl sulfoxide are preferably used, and methanol is more preferably used.

  As the volume of the solvent mixed with the extract, any volume may be used. As the volume of the solvent to be mixed with the extract, it is preferable to use an excessive amount of solvent with respect to the extract from the viewpoint of reducing the viscosity by adding the solvent. For example, it is preferable to add 90 ml of solvent to 10 grams of the extract.

  The extract and the solvent may be mixed by any method. For example, the extract and the solvent may be mixed by adding the solvent to the extract and stirring at room temperature, or by adding the extract to the solvent and stirring at room temperature. Also good.

  Any method may be used for the solid-liquid separation. As the solid-liquid separation, for example, celite filtration, filtration using arbitrary filter paper, centrifugation, or the like is preferably used, and celite filtration is more preferred.

  In the adsorption process, the separation liquid from which the solvent has been removed in the solvent removal process is brought into contact with the strongly basic anion exchange resin, so that shikimic acid contained in the separation liquid is adsorbed on the strong basic anion exchange resin.

  Here, as the strongly basic anion exchange resin, any strongly basic anion exchange resin that adsorbs shikimic acid may be used. As the strongly basic anion exchange resin, for example, Amberlite (registered trademark), Diaion (registered trademark) or the like is preferably used. Further, as the strongly basic anion exchange resin, it is more preferable to use Amberlite IRA400 Cl-, IRA400 OH-, IRA400 Ac-, or the like.

  In the washing step, the ionic liquid remaining in the strong base anion exchange resin is removed by washing the strong base anion exchange resin having shikimic acid adsorbed in the adsorption step with deionized water. The capacity of deionized water used in the washing step may be any volume, and it is preferable to use an excessive amount of deionized water. For example, it is preferable to use 280 ml or more of deionized water with respect to the separated liquid “0.86 g” from which the solvent has been removed by the removal process.

  In the obtaining step, shikimic acid is obtained from the strongly basic anion exchange resin washed in the washing step. Specifically, in the obtaining step, shikimic acid is obtained by passing the eluent through a strongly basic anion exchange resin and removing the acetic acid from the eluent after the passage. For example, as an eluent in the acquisition step, any eluent that elutes shikimic acid adsorbed on a strongly basic anion exchange resin may be used. As the eluent in the acquisition step, for example, acetic acid or formic acid is preferably used, and acetic acid is more preferable.

  The case where acetic acid is used as the eluent will be further described. The concentration of acetic acid used as the eluent may be any concentration, preferably in the range of 10 to 50% by weight, and more preferably 25% by weight.

  In the collection step, the deionized water after washing the strongly basic anion exchange resin in the washing step is collected, and the collected deionized water is removed to recover the ionic liquid. Any method may be used as a method for removing the solvent. As the solvent removal, for example, vacuum concentration is preferable.

(Substance acquisition method and substance production method)
The disclosed substance acquisition method from ionic liquid and substance production method from ionic liquid include an adsorption step, a washing step, and an acquisition step.

  As described in detail below, according to the disclosed substance acquisition method from an ionic liquid and substance production method from an ionic liquid, a substance dissolved in a nonvolatile ionic liquid can be reliably obtained. For example, when shikimic acid is extracted using an ionic liquid as an extraction solvent, the shikimic acid extracted into the ionic liquid can be obtained with high efficiency.

In the adsorption step, an ionic liquid in which an arbitrary substance is dissolved is brought into contact with the ion exchange resin, so that the substance contained in the ionic liquid is adsorbed on the ion exchange resin. The arbitrary substance may be any compound that is adsorbed on the ion exchange resin. When the ion exchange resin is an anion exchange resin, for example, any compound having a carboxylic acid may be used. In addition, when the ion exchange resin is a cation exchange resin, for example, any compound having an amino acid (NH ₃ ) may be used. For example, when an arbitrary substance is shikimic acid, any strongly basic anion exchange resin is used as the ion exchange resin. About another point, it is the same as that of the adsorption process in the shikimic acid acquisition method and shikimic acid manufacturing method which were mentioned above, and abbreviate | omits description.

  In the washing step, the ion exchange resin in which an arbitrary substance is adsorbed in the adsorption step is washed with deionized water, thereby removing the ionic liquid remaining in the ion exchange resin. In the acquisition step, an arbitrary substance is acquired from the ion exchange resin that has been cleaned in the cleaning step. About the other point of a washing process and an acquisition process, it is the same as that of a washing process and an acquisition process in a shikimic acid acquisition method and a shikimic acid manufacturing method mentioned above, and omits explanation.

  Hereinafter, the disclosed shikimic acid acquisition method and shikimic acid production method will be described in more detail with reference to examples. However, the disclosed shikimic acid acquisition method and shikimic acid production method are not limited to the following examples.

[Example 1]
[Extraction process]
Green leaves of female ginkgo were coagulated with liquid nitrogen, and the coagulated green leaves were pulverized using a mortar. Thereafter, 2.62 g of green leaf pulverized product is added to 7.49 g of 1-butyl-3-methylimidazolium chloride (also referred to as “[bmim] Cl”) which becomes liquid at room temperature, and stirred at 130 ° C. for 1 hour. Extraction was performed. Thereafter, 90 ml of methanol was added to the extract and stirred at room temperature for 30 minutes to lower the viscosity of the extract, followed by Celite filtration, and methanol contained in the filtrate was removed by concentration under reduced pressure. 9.14g of filtrate after methanol removal was obtained by removing methanol by vacuum concentration.

  Thereafter, reverse-phase HPLC (High Performance Liquid Chromatography) analysis was performed under the following analysis conditions, and the concentration of shikimic acid contained in the filtrate after methanol removal was quantified using an absolute calibration curve method. The extraction rate of shikimic acid extracted from the pulverized plant by the extraction treatment will be described later using Table 1.

[HPLC analysis conditions]
Column: COSMOSIL (registered trademark) 5C18-Ar-II (Nacalai Tesque)
Solvent: 20 mM KH ₂ PO ₄ (pH 2.5)
Flow rate: 0.15 ml / min
Column temperature: 40 ° C
UV detection: 240 nm

  FIG. 1 is a diagram showing an example of a chart obtained by reverse phase HPLC analysis. (SA (Shikimic Acid) + IL (Ionic Liquid)) in FIG. 1 shows a chart obtained for the filtrate after methanol removal. Note that (SA) in FIG. 1 is a chart obtained for a sample containing only shikimic acid, and (IL) in FIG. 1 is a chart obtained for a sample containing only [bmim] Cl. (SA) and (IL) in FIG. 1 were prepared using a standard sample. As shown in (SA + IL) in FIG. 1, the filtrate after removing methanol contains [bmim] Cl and shikimic acid.

  In addition, when the HPLC analysis was performed with respect to the extract before mixing with methanol, the extraction rate similar to the filtrate after methanol removal was obtained. In other words, there was no change in the extraction rate of shikimic acid by adding methanol.

[Examples 2 to 12]
As shown in Table 1, Example 1 was the same as Example 1 except that [bmim] Cl “z” g was added with green leaf pulverized product “x” g and stirred at “y” ° C. for 1 hour. A similar extraction process was performed. The extraction rate of shikimic acid in Examples 2 to 12 is shown in Table 1.

[Example 13]
After removing methanol, 0.86 g of the mixture of filtrates after removal of methanol obtained in Examples 10 to 12 was passed through a column packed with strongly basic anion exchange resin (Amberlite IRA400 Cl ⁻ ). Shikimic acid contained in the filtrate was adsorbed on the column. Thereafter, 280 ml of deionized water was passed through the column to wash away [bmim] Cl remaining in the column. Thereafter, by passing 56 ml of acetic acid having a concentration of 25% by weight as an eluent, shikimic acid adsorbed on the column was eluted. Thereafter, the eluate was evaporated to dryness to obtain 6.2 mg of shikimic acid. It was confirmed using NMR (Nuclear Magnetic Resonance) spectrum that the obtained substance was shikimic acid and did not contain [bmim] Cl. The filtrate 0.86 g after the removal of methanol contained 7.1 mg of shikimic acid as determined by the absolute calibration curve method. As a result, the isolation rate of shikimic acid from the filtrate after removal of methanol was “87%”. As a result, the yield of shikimic acid from the green leaves of Ginkgo biloba when extracted at 150 degrees was “(3.2%) × 0.87 = 2.8%”.

[Comparative Examples 1-5]
As shown in Table 2, the pulverized green leaf “x” g was added to “α” g of methanol, and extracted by stirring with refluxing at 80 ° C. for 1 hour, and the extract was subjected to Celite filtration. Except having performed, the extraction process similar to Example 1 was performed. The extraction rate of shikimic acid in Comparative Examples 1 to 5 is shown in Table 2.

[Comparative Example 6]
As shown in Table 2, 2.5 g of pulverized green leaves was added to 10 g of ethanol, extracted by stirring at 80 ° C. while refluxing for 1 hour, and celite filtration was performed on the extract. The same extraction process as in Example 1 was performed. The extraction rate of shikimic acid in Comparative Example 6 is shown in Table 2.

[Comparative Example 7]
As shown in Table 2, 2.5 g of pulverized green leaves was added to 12.5 g of deionized water, and extraction was performed by stirring at 100 ° C. for 1 hour while refluxing. Celite filtration was performed on the extract. Except having performed, the extraction process similar to Example 1 was performed. The extraction rate of shikimic acid in Comparative Example 7 is shown in Table 2.

[Comparative Example 8]
As shown in Table 2, 2.5 g of pulverized green leaves were added to 10 g of DMF (dimethylformamide) and extracted by stirring at 150 ° C. for 1 hour while refluxing. The same extraction process as in Example 1 was performed except that filtration was performed. The extraction rate of shikimic acid in Comparative Example 8 is shown in Table 2.

[Comparative Examples 9 to 11]
As shown in Table 3, with respect to the extracts obtained in Comparative Examples 3 to 5, the weight part of the extract “0.11” is added to the ionic liquid “0.75”, HPLC analysis was performed, and shikimic acid concentration was quantified using an absolute calibration curve method. The extraction rates quantified for Comparative Examples 9 to 11 are shown in Table 3.

  It supplements about the ratio of the weight part "0.11" of the extract in Comparative Examples 9-11, and an ionic liquid weight part "0.75". The ratios in Comparative Examples 9 to 11 are values calculated from the weight of the filtrate after removal of methanol in Examples. The ionic liquid has a non-volatile characteristic, and the weight of the ionic liquid contained in the filtrate after removal of methanol is the same as that when the pulverized green leaves are added. As a result, when the weight of the filtrate after removing methanol is “8.6 g”, 7.5 g is the weight of the ionic liquid, and “1.1 g” is the weight of the extract. Based on this, the concentration of shikimic acid was quantified in the sample subjected to HPLC analysis, with the same weight ratio between the ionic liquid and the extract.

[Extraction rate]
As shown in Table 1, shikimic acid was extracted from the green leaves of female ginkgo biloba by extraction using an ionic liquid as an extraction solvent. Further, as shown in Example 2 to Example 4 in Table 1, when the ratio of green leaves to [bmim] Cl was changed, the ratio of green leaves to [bmim] Cl was “1: 1”. Compared with "1: 9" and "1: 3", the extraction rate was the highest. Moreover, as shown in Examples 1 and 5 to 12 in Table 1, the extraction rate was improved by increasing the temperature at which extraction was performed.

  As shown in Table 2, the extraction rate was around “1%” when extraction was performed using water or a general organic solvent regardless of the difference in temperature and solvent. The extraction rate shown in Table 2 is the extraction rate obtained when each solvent is extracted under reflux conditions, and is the maximum temperature at which extraction can be performed using each solvent. In other words, each extraction rate shown in Table 2 is a value that makes it difficult to improve the extraction rate by increasing the temperature.

  In addition, as shown in Table 1, in Examples 1-12, when using the weight part 3 of an ionic liquid with respect to the weight part 1 of the ginkgo green leaf, when the ginkgo green leaf was added to the solvent, a ginkgo Green leaves soaked in a solvent in ionic liquid. On the other hand, when a general organic solvent or water is used instead of an ionic liquid, a general organic solvent or water part by weight 3 is used for the weight part 1 of the ginkgo green leaf. The green leaves of Ginkgo biloba were not sufficiently immersed in various organic solvents and water. Based on this, when using a general organic solvent instead of an ionic liquid, “4” was used as a weight part of a general organic solvent with respect to weight part 1 of green leaves of Ginkgo biloba. When water was used instead of the ionic liquid, “5” was used as the weight part of water with respect to the weight part 1 of the green leaf of Ginkgo biloba. That is, as shown in Table 1 and Table 2, when an ionic liquid is used as an extraction solvent, the weight part of the ionic liquid with respect to the weight part of green leaves of ginkgo biloba is used when water or a general organic solvent is used. It is possible to make it smaller than the weight part of the solvent with respect to the weight part of the green leaves of Ginkgo biloba.

  FIG. 2 is a diagram showing the difference in the extraction rate of shikimic acid depending on the extraction solvent. In the example illustrated in FIG. 2, the vertical axis indicates “extraction rate” and the horizontal axis indicates “temperature”. As shown in FIG. 2, when the ratio of green leaves to [bmim] Cl was “1: 3”, the extraction rate was higher than in Comparative Examples 1-8. For example, in Example 3 where the temperature at which extraction is performed is 150 ° C., the extraction rate is “3.3%”, which is three times as much as that of Comparative Examples 1 to 8 where the extraction rate is about “1%”. The acid can be extracted.

  Moreover, according to Table 3, the extraction rate of Comparative Examples 9 to 11 is “1.4 times” compared to Comparative Examples 3 to 5. This is considered to be due to the influence of the peak derived from the ionic liquid detected in HPLC, resulting in a large peak derived from shikimic acid, resulting in an increase in the concentration of shikimic acid as the quantitative result.

  Considering this point, the case where the extraction rate of the example is “1 / 1.4” will be examined. Even in this case, in the extraction process of Example 3 in which the extraction temperature is 150 ° C., the extraction rate is “(3.3%) / (1.4) = 2.3%”, and the extraction rate is “ It was shown that it was possible to extract shikimic acid twice as much as the comparative example of about 1%.

Claims (5)

An extraction step of adding ginkgo biloba leaves to an ionic liquid capable of dissolving cellulose and extracting from the ginkgo leaves ;
The extract obtained by the extraction step is mixed with a solvent that is compatible with the ionic liquid and can dissolve shikimic acid, and insoluble matters are removed by solid-liquid separation from the mixture of the extract and the solvent. A solid-liquid separation step of recovering the separated liquid,
An adsorption step for adsorbing shikimic acid contained in the separated liquid to the strongly basic anion exchange resin by bringing the separated liquid recovered by the solid-liquid separation step into contact with the strongly basic anion exchange resin;
A washing step of removing the ionic liquid remaining in the strongly basic anion exchange resin by washing the strongly basic anion exchange resin having shikimic acid adsorbed in the adsorption step with deionized water; ,
An acquisition step of acquiring the shikimic acid from the strongly basic anion exchange resin washed by the washing step. The shikimic acid acquisition method according to claim 1, wherein the ionic liquid is 2 to 8 parts by weight with respect to 1 part by weight of the ginkgo leaf .   The method for obtaining shikimic acid according to claim 1 or 2, wherein the extraction step is performed at 120 to 170 ° C. It further comprises a recovery step of recovering the ionic liquid by recovering the deionized water after cleaning the strongly basic anion exchange resin in the cleaning step and removing the recovered deionized water. shikimate acquisition method according to any one of claims 1 to 3. An extraction step of adding ginkgo biloba leaves to an ionic liquid capable of dissolving cellulose and extracting from the ginkgo leaves ;
The extract obtained by the extraction step is mixed with a solvent that is compatible with the ionic liquid and can dissolve shikimic acid, and insoluble matters are removed by solid-liquid separation from the mixture of the extract and the solvent. A solid-liquid separation step of recovering the separated liquid,
An adsorption step for adsorbing shikimic acid contained in the separated liquid to the strongly basic anion exchange resin by bringing the separated liquid recovered by the solid-liquid separation step into contact with the strongly basic anion exchange resin;
A washing step of removing the ionic liquid remaining in the strongly basic anion exchange resin by washing the strongly basic anion exchange resin having shikimic acid adsorbed in the adsorption step with deionized water; ,
An acquisition step of acquiring the shikimic acid from the strongly basic anion exchange resin washed by the washing step.

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