JP7600524B2 - Method for decomposing glycosides, method for producing aglycones, and method for decomposing sphingoglycolipids - Google Patents

Description

The present invention relates to a method for decomposing an ester compound and a method for producing a compound having a hydroxyl group.

Ester compounds having an ester structure obtained by dehydration condensation of an organic acid and a compound having a hydroxyl group are widely found in nature and are also widely used industrially as thermoplastic resins and thermosetting resins. Naturally occurring ester compounds include glycosides in which a sugar and an aglycone, which is the non-sugar portion, are bonded via a glycosidic bond.

Glycosides are found in the flowers, leaves, roots, stems, fruits, seeds, etc. of various plants, including citrus fruits and beans, and aglycones are obtained by hydrolysis of glycosides. Aglycones have different characteristics and effects depending on the type, but among aglycones, polyphenols generally have strong antioxidant effects. For example, polymethoxyflavones, a type of polyphenol found in citrus fruits, are known to have antioxidant, carcinogenic, antibacterial, antiviral, antiallergic, melanin production inhibitory, and blood sugar inhibitory effects, and are expected to be used in a variety of applications such as medicines, health foods, and cosmetics.

A method for decomposing glycosides, which are ester compounds, to obtain aglycones is known that involves contacting the glycosides with high-temperature, high-pressure water (Patent Document 1).

WO 2008/155890

However, conventional methods for decomposing ester structures involve hydrolysis using water as a solvent, and the epoxy and acrylic compounds produced by decomposition of ester compounds, as well as aglycones such as polyphenols, are virtually insoluble in water, resulting in low processing efficiency and yield during separation and purification after processing.

The present invention has been made in consideration of the problems of the above-mentioned conventional technology, and aims to provide a method for decomposing an ester compound that can efficiently decompose an ester compound into a compound having a hydroxyl group, and a method for producing a compound having a hydroxyl group that can improve the yield of the compound having a hydroxyl group.

To achieve the above object, the present invention provides a method for decomposing an ester compound, which includes a decomposition step of decomposing a raw material containing an ester compound having an ester structure obtained by dehydration condensation of an organic acid and a compound having a hydroxyl group in the presence of a solvent, the solvent including a non-aqueous solvent other than water having an ionic product of 23 or less at 23°C.

The above method allows the ester compound to be efficiently decomposed. Since the ester structure is decomposed by hydrolysis, it is generally considered that the decomposition occurs by acid treatment or hydrothermal treatment of the aqueous solution. However, although the reason is unclear, the inventors have found that the decomposition of the ester structure is promoted when the solvent contains a non-aqueous solvent other than water that has an ionic product of 23 or less at 23°C. Therefore, by using the above method, it is possible to efficiently produce a compound having a hydroxyl group at low cost.

In the decomposition step, the raw material is heated and pressurized in the presence of a solvent, and the heating and pressurizing treatment may be carried out at a temperature of 110°C or higher and 400°C or lower. This allows the ester compound to be decomposed particularly efficiently.

In the above method, the ester compound may contain a glycoside. According to the above method, the glycoside can be decomposed particularly efficiently. The glycoside may contain a polyphenol glycoside, a flavonoid glycoside, a sudachitin glycoside, a demethoxysudachitin glycoside, a quercetin glycoside, an anthocyanin, or a glycosylceramide. According to the above method, these glycosides can be decomposed particularly efficiently.

The present invention also provides a method for producing a compound having a hydroxyl group, comprising a decomposition step of decomposing an ester compound by the method of the present invention, and a separation step of separating a compound having a hydroxyl group from the decomposition product obtained in the decomposition step. According to this production method, a compound having a hydroxyl group can be produced efficiently at a high yield at low cost. When water or the like in which an ester compound is not dissolved is used as a solvent, the compound having a hydroxyl group produced by the decomposition of the ester compound precipitates. Therefore, in the separation step, it is necessary to dissolve the precipitated compound having a hydroxyl group in a solvent in which the compound having a hydroxyl group is dissolved, and then remove the insoluble matter by filtration or the like. However, in the method according to the present invention, since the solvent contains a non-aqueous solvent other than water having an ionic product of 23 or less at 23°C, the compound having a hydroxyl group does not precipitate after the decomposition step, and there is no need to dissolve the compound having a hydroxyl group in a new solvent in the separation step. Therefore, a compound having a hydroxyl group can be produced efficiently.

The present invention provides a method for decomposing an ester compound that can efficiently decompose an ester compound into a compound having a hydroxyl group, and a method for producing a compound having a hydroxyl group that can improve the yield of the compound having a hydroxyl group.

The present invention will be described in detail below with reference to preferred embodiments. However, the present invention is not limited to the following embodiments.

In this specification, a numerical range indicated using "~" indicates a range including the numerical values before and after "~" as the minimum and maximum values, respectively. In the numerical ranges described in stages in this specification, the upper limit or lower limit of a numerical range in a certain stage can be arbitrarily combined with the upper limit or lower limit of a numerical range in another stage. In the numerical ranges described in this specification, the upper limit or lower limit of the numerical range may be replaced with a value shown in the examples. "A or B" may include either A or B, or may include both. Unless otherwise specified, the materials exemplified in this specification may be used alone or in combination of two or more types.

(Method for decomposing ester compounds)
The method for decomposing an ester compound according to this embodiment (hereinafter also referred to as the "decomposition method of this embodiment") includes a decomposition step of decomposing an ester compound having an ester structure obtained by dehydration condensation of an organic acid and a compound having a hydroxyl group, in the coexistence of a solvent, and the solvent includes a nonaqueous solvent other than water having an ionic product of 23 or less at 23°C.

In the decomposition method of this embodiment, the raw material may be heated and pressurized in the presence of a solvent in the decomposition step. The heating and pressurizing treatment may be a method in which the raw material is dissolved/dispersed in a solvent and heated in a sealed container at a temperature above the boiling point at normal pressure to decompose the raw material. In this embodiment, normal pressure means 0.1 MPa (atmospheric pressure).

An ester compound is a compound having an ester structure obtained by dehydration condensation of an organic acid and a compound having a hydroxyl group. Examples of organic acids include sugar, acetic acid, citric acid, and other organic acids. Examples of compounds having a hydroxyl group include polyphenol aglycone, phenol, and alcohol. Examples of ester compounds include glycosides and polyesters, and among them, glycosides can be preferably used. Glycosides are hydrophilic compounds in which sugar and aglycone, which is the non-sugar portion, are bonded by a glycosidic bond. Examples of such glycosides include, but are not limited to, phenol glycosides, coumarin glycosides, flavonoid glycosides, chalcone glycosides, anthocyanidin glycosides, anthraquinone glycosides, indole glycosides, and sphingoglycolipids.

Among polyphenol glycosides, flavonoid glycosides are hydrophilic compounds having a structure in which a flavonoid and a sugar are bound by a glycosidic bond. The flavonoids (aglycones) that are the source of flavonoid glycosides are aromatic compounds with a phenylchroman skeleton as a basic structure, and examples of such compounds include flavones, flavonols, flavanones, flavanonols, isoflavones, anthocyanins, flavanols, chalcones, and aurones. Among these, the flavonoid may be a polymethoxyflavone, which is a flavone.

Examples of polymethoxyflavones include sudachitin, demethoxysudachitin, nobiletin, tangeretin, pentamethoxyflavone, tetramethoxyflavone, and heptamethoxyflavone. Among these, the polymethoxyflavone may be sudachitin or demethoxysudachitin.

The flavonoids may also include hesperetin or anthocyanidins.

Glycosphingolipids are formed by binding sugar and sphingosine via a glycosidic bond. An example of a glycosphingolipid is glucosylceramide.

The sugars that are the source of flavonoid glycosides are not particularly limited, and include known sugars that can be bound to the above-mentioned flavonoids via glycosidic bonds to form glycosides.

The raw material used in the decomposition method of this embodiment may contain other components besides the ester compound. Examples of other components include flavonoids, water-soluble dietary fiber, poorly soluble dietary fiber, and sugars. The content of the ester compound in the raw material is preferably 0.1 mass% or more, more preferably 0.25 to 30 mass%, even more preferably 0.3 to 15 mass%, and particularly preferably 0.5 to 5 mass%, based on the total solid content of the raw material. When the raw material further contains a flavonoid, the content of the flavonoid glycoside is preferably 0.25 mass parts or more, more preferably 0.5 to 100 mass parts, and even more preferably 5 to 50 mass parts, per 1 mass part of the flavonoid content.

When the ester compound contains a glycoside, the flowers, leaves, roots, stems, fruits, seeds, etc. of plants and seaweeds can be used as the raw material for the glycoside. In particular, the peel contains a lot of polymethoxyflavones and their glycosides, so the squeezed residue of citrus fruits can be suitably used. The raw material may be a dried powder obtained from citrus fruits, or a dried powder obtained from citrus peels. Examples of citrus fruits include sudachi, unshu mandarin oranges, ponkan, and shikuwasa. The citrus fruit may be sudachi, which contains a lot of polymethoxyflavones such as sudachitin and demethoxysudachitin, and their glycosides.

The heating and pressurizing treatment can be carried out by sealing the raw materials together with the solvent in a pressure-resistant sealed container and heating the sealed container at a temperature above the boiling point of the solvent at normal pressure. By heating the reaction liquid containing the raw materials and the solvent in the sealed container, the inside of the sealed container becomes a heated and pressurized environment, and a decomposition reaction of the ester structure occurs. The heating and pressurizing treatment may be carried out while stirring the raw materials and the solvent. There are no particular limitations on the pressure-resistant sealed container, and for example, a known container that can be used for hydrothermal treatment using water as a solvent can be used. For example, an autoclave can be used as the pressure-resistant sealed container.

The solvent used in the decomposition method of this embodiment includes non-aqueous solvents other than water that have an ionic product of 23 or less at 23°C. Examples of such non-aqueous solvents include, but are not limited to, alcohols such as methanol, ethanol, and propanol, ethylene glycol, formaldehyde, butylaldehyde, organic acids such as formic acid and acetic acid, ethanolamine, and ethylenediamine. The non-aqueous solvent may be used alone or in combination of two or more. Among these, methanol and ethanol are preferred as non-aqueous solvents because they can further promote the decomposition of glycosides. The solvent used in the decomposition method of this embodiment may or may not contain water.

The ionic product at 23°C of a non-aqueous solvent other than water that has an ionic product of 23 or less at 23°C may be 18 or less, or may be 12 or less.

The solvent used in the decomposition method of this embodiment may contain other solvents that are different from non-aqueous solvents other than water that have an ion product of 23 or less at 23°C. Such other solvents include water and non-aqueous solvents other than water that have an ion product of more than 23 at 23°C. Examples of non-aqueous solvents other than water that have an ion product of more than 23 at 23°C include toluene and hexane.

The proportion of non-aqueous solvent other than water having an ionic product of 23 or less at 23°C contained in the solvent used in the decomposition method of this embodiment may be 10% by mass or more, 50% by mass or more, or 100% by mass, based on the total amount of the solvent.

The amount of the solvent used in the decomposition method of this embodiment is not particularly limited as long as it is an amount sufficient to decompose the ester compound, but the solid content of the raw material may be 1 part by mass or more, 2 parts by mass or more, 4 parts by mass or more, or 5 parts by mass or more relative to 100 parts by mass of the solvent, and may be 100 parts by mass or less, 33 parts by mass or less, 25 parts by mass or less, 18 parts by mass or less, or 11 parts by mass or less. In addition, the content of the solid content of the raw material in the reaction liquid (raw material concentration) may be 1.0 mass% or more, 2.0 mass% or more, 3.8 mass% or more, or 4.8 mass% or more based on the total amount of the reaction liquid, and may be 50 mass% or less, 25 mass% or less, 20 mass% or less, 15 mass% or less, or 10 mass% or less. When the amount of the solvent or the raw material concentration is within the above range, the decomposition of the ester compound can be efficiently performed. In addition, when the ratio of the solid content of the raw material to the solvent or the raw material concentration is equal to or less than the above upper limit, the yield tends to be improved when a substance is extracted from the decomposition product obtained by the decomposition method of this embodiment.

It is preferable that the solvent used in the decomposition method of this embodiment does not contain inorganic acids such as hydrochloric acid, sulfuric acid, and nitric acid. When the solvent used in the decomposition method of this embodiment contains an inorganic acid and the heating and pressurizing treatment is performed in the decomposition method of this embodiment, it is not preferable because highly toxic organic salt compounds, organic nitrogen compounds, and organic sulfur compounds are likely to be generated by the heating and pressurizing treatment in a closed container. In addition, when the solvent used in the decomposition method of this embodiment contains an inorganic acid, there is a problem that the inorganic acid may remain in the product, and a process for sufficiently removing the inorganic acid is required to prevent the inorganic acid from remaining in the product, resulting in high costs. The content of the inorganic acid in the solvent used in the decomposition method of this embodiment is preferably 1% by mass or less, 0.1% by mass or less, or 0.01% by mass or less based on the total amount of the solvent and raw materials.

When the heating and pressurizing treatment is performed in the decomposition treatment step, the reaction conditions for the heating and pressurizing treatment are not particularly limited, but may be, for example, 110 to 400°C and 0.5 to 20 hours. The optimum reaction temperature varies depending on the solvent, but is preferably 110 to 350°C, more preferably 120 to 300°C, and even more preferably 140 to 250°C. If the reaction temperature is 110°C or higher, the reaction tends to occur more smoothly, and if it is 400°C or lower, carbonization of the raw material and compounds containing hydroxyl groups such as flavonoids tends not to proceed, and the yield tends to be improved. The reaction time is preferably 0.5 to 20 hours, and more preferably 1 to 10 hours. If the reaction time is 0.5 hours or more, the reaction tends to proceed more easily, and if it is 20 hours or less, it tends to be easier to balance the progress of the reaction and the cost.

When a heating and pressurizing treatment is performed in the decomposition step and the solvent is a mixed solvent containing two or more solvents, the reaction temperature may be a temperature that exceeds the boiling point of the solvent with the lower boiling point in the mixed solvent at normal pressure (i.e., the boiling point taking into account the boiling point elevation, etc.).

From the viewpoint of improving the yield, it is preferable to carry out the heating and pressurizing treatment under conditions of low temperature (e.g., less than 250°C) and long time (e.g., 1 hour or more). If the reaction temperature is high, bumping of the reaction liquid is likely to occur during cooling after the reaction, and if bumping occurs, the reaction liquid will scatter outside the container containing the reaction liquid, which tends to reduce the yield. In addition, if cooling is performed to prevent the above-mentioned bumping from occurring, a long cooling time is required, which reduces the work efficiency. This problem of a long cooling time is a disadvantage especially in mass production. From the viewpoint of improving such a problem, it is preferable to carry out the heating and pressurizing treatment under conditions of low temperature and long time. Even if the heating and pressurizing treatment is performed at a low temperature, sufficient decomposition can be achieved by extending the reaction time. In addition, the heating and pressurizing treatment performed under conditions of low temperature and long time can shorten the overall process time, including the cooling time after the heating and pressurizing treatment, compared to the heating and pressurizing treatment performed under conditions of high temperature and short time.

By carrying out the heating and pressure treatment under the above conditions, the ester structure contained in the ester compound molecule can be efficiently decomposed.

(Method for producing a compound having a hydroxyl group)
The method for producing a compound having a hydroxyl group according to the present embodiment includes a decomposition step of decomposing an ester compound, and an extraction step of separating the compound having a hydroxyl group from the decomposition product obtained in the decomposition step. The decomposition step is a step of decomposing an ester compound having an ester structure by the above-mentioned method for decomposing an ester compound according to the present embodiment.

In the separation process, the target substance is separated from the decomposition product obtained in the decomposition process. In addition to the target substance, the decomposition product contains raw materials that remain undecomposed. If the decomposition product has a different solubility in the raw materials, one will be solid and the other will be obtained as a solution. After heat treatment, solid-liquid separation by filtration or centrifugation can be performed to obtain a component containing a high concentration of the target substance, which can be concentrated. Furthermore, the target substance can be further extracted and refined by drying and solidifying it, and then extracting it with another solvent with high solubility.

The above method allows for the efficient production of compounds having hydroxyl groups, such as aglycones, with high yields.

The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

Example 1
2 g of Sudachi peel extract powder (manufactured by Ikeda Yakuso Co., Ltd.) with a sudachitin content of 1000 ppm by mass and a glycoside-derived sudachitin content of 9000 ppm by mass was dissolved/dispersed in 50 g of ethanol (special grade, purity 99.5%, manufactured by Wako Pure Chemical Industries, Ltd.) as a solvent, and sealed in a Teflon (registered trademark) container with a capacity of 100 ml, and the Teflon (registered trademark) container was further placed in a stainless steel pressure-resistant container, and the pressure-resistant container was sealed. In the sealed pressure-resistant container, the solution in the Teflon (registered trademark) container was heated with a heater to a temperature of 180° C. while stirring at a rotation speed of 600 rpm using a magnetic stirrer. After reaching 180° C., the solution was heated at 180° C. for 60 minutes while continuing to stir. Thereafter, heating and stirring were stopped and the solution was naturally cooled to room temperature (25° C.). The maximum temperature reached during the heat treatment was 181° C.

After cooling, the solution and solids were filtered under reduced pressure using a hydrophilic PTFE membrane filter with 0.2 μm mesh (Merck Millipore, product name: Omnipore 0.2 μm JG) with a diaphragm pump. Since the separated solution contained high concentrations of decomposed flavonoids (sudachitin and demethoxysudachitin), the resulting solution was placed in a 200 cc glass beaker and dried in an oven at 50°C for 12 hours, obtaining 0.17 g of powdered flavonoid concentrated powder 1.

Example 2
The same procedure as in Example 1 was repeated except that methanol (special grade, purity 99.5%, manufactured by Wako Pure Chemical Industries, Ltd.) was used instead of ethanol as the solvent, to obtain 0.16 g of a powdered flavonoid-enriched powder 2.

Example 3
The same procedure as in Example 1 was repeated except that isopropyl alcohol (manufactured by Wako Pure Chemical Industries, Ltd.) was used instead of ethanol as the solvent, to obtain 0.13 g of a powdered flavonoid-enriched powder 3.

Example 4
The same procedure as in Example 1 was repeated except that butyraldehyde (manufactured by Wako Pure Chemical Industries, Ltd.) was used instead of ethanol as the solvent, to obtain 0.16 g of a powdered flavonoid-enriched powder 4.

Example 5
Onion skin powder (Awajishima onion powder, Shizen Kenkou Co., Ltd.) was dispersed in a mixed solution of ultrapure water and ethanol (mixture ratio: ultrapure water:ethanol = 50:50) to a concentration of 5% by weight to obtain a dispersion of onion skin powder. The obtained dispersion was heated at 60 ° C for 3 hours to extract quercetin aglycone and quercetin glycoside contained in the onion skin powder. After extraction, solid-liquid separation was performed using a centrifuge at 10,000 rpm for 10 minutes, and the supernatant was separated and dried in an oven to obtain a dry powder. The obtained dry powder was pulverized in an agate mortar to obtain an onion skin extract powder containing 7% by mass of quercetin aglycone and 1% by mass of quercetin glycoside.

0.3 g of powdered flavonoid concentrated powder 5 was obtained in the same manner as in Example 1, except that 1 g of the onion skin extract powder was used instead of 2 g of sudachi peel extract powder as a raw material.

Example 6
The same procedure as in Example 1 was repeated, except that 0.2 g of soybean-derived glucosylceramide powder (manufactured by Wako Pure Chemical Industries, Ltd.) was used instead of 2 g of sudachi peel extract powder as a raw material, to obtain 0.18 g of powdered ceramide concentrated powder 6.

(Example 7)
The same procedure as in Example 5 was repeated except that butyraldehyde was used as the solvent instead of ethanol, to obtain 0.28 g of a powdered flavonoid-enriched powder 7.

(Example 8)
The same procedure as in Example 6 was repeated except that butyraldehyde was used as the solvent instead of ethanol, to obtain 0.17 g of concentrated ceramide powder 8 in powder form.

(Comparative Example 1)
The same procedure as in Example 1 was repeated except that toluene having an ionic product of more than 23 was used as the solvent instead of ethanol, to obtain 0.15 g of powder 9 in powder form.

<Measurement of aglycone concentration>
The concentration of sudachitin, quercetin or ceramide aglycone in the concentrated powder obtained in each Example and Comparative Example was measured by the following method. First, 0.1 g of concentrated powder was dissolved/dispersed in ethanol so that the dilution ratio was 500 times, and filtered through a PTFE filter with a pore size of 0.1 μm to obtain an ethanol solution. The components of this ethanol solution were analyzed by high performance liquid chromatography (HPLC). A calibration curve was created using a standard purified sample of each flavonoid and a standard purified sample of ceramide aglycone as a standard substance, and the concentrations of sudachitin, quercetin and ceramide aglycone in the concentrated powder were estimated using the calibration curve. The HPLC device used was a "Chrome Master" manufactured by Hitachi High-Tech. The results are summarized in Table 1.

As shown in Table 1, in all of Examples 1 to 8, the aglycone concentration and yield in the concentrated powder were increased compared to Comparative Example 1, and it was found that aglycone was newly generated by decomposition of glycoside, and the aglycone concentration and yield could be improved. On the other hand, in Comparative Example 1, the glycoside was not decomposed in toluene, which has an ion product at room temperature of more than 23, and the concentration was only the same as that of the flavonoid in the raw material, and no improvement in concentration was observed.

Claims (4)

A decomposition step of decomposing a raw material containing a glycoside in the presence of a solvent,
In the decomposition step, the raw material is subjected to a heating and pressurizing treatment in the presence of a solvent,
The heating and pressurizing treatment is carried out by sealing the raw material together with the solvent in a pressure-resistant sealed container and heating the sealed container at a temperature exceeding the boiling point of the solvent at normal pressure;
The glycoside is at least one selected from the group consisting of quercetin glycoside, sudachitin glycoside, and demethoxysudachitin glycoside,
A method for decomposing a glycoside , wherein the solvent comprises a non-aqueous solvent other than water having an ionic product of 23 or less at 23°C. The decomposition method according to claim 1, wherein the heating and pressurizing treatment is carried out at a temperature of 110°C or higher and 400°C or lower. A decomposition step of decomposing the glycoside by the method according to claim 1 or 2 ;
and an extraction step of extracting an aglycone from the decomposition product obtained in the decomposition step. A decomposition step of decomposing a raw material containing sphingoglycolipids in the presence of a solvent,
In the decomposition step, the raw material is subjected to a heating and pressurizing treatment in the presence of a solvent,
The heating and pressurizing treatment is carried out by sealing the raw material together with the solvent in a pressure-resistant sealed container and heating the sealed container at a temperature exceeding the boiling point of the solvent at normal pressure;
A method for decomposing sphingoglycolipids, wherein the solvent comprises a non-aqueous solvent other than water having an ionic product of 23 or less at 23°C.