JPH01242578A - Extraction of readily degradable organic compound - Google Patents

Abstract

PURPOSE:To enable the extraction of an organic compound liable to be degraded by conventional solvent extraction, without casing the degradation of the compound and to improve the extraction efficiency, by extracting a substance containing readily degradable organic compound with supercritical carbon dioxide. CONSTITUTION:A substance containing a readily degradable organic compound such as a natural compound containing epoxy ring in the structure is extracted with supercritical carbon dioxide to enable the extraction and separation of the readily degradable organic compound keeping the epoxy ring and without causing the degradation using a general solvent extraction method. The above natural compound is e.g., aculeatin existing in the root sheath of SARUKAKEMIKAN (Toddalia asiatica, a plant of family Rutanceae) which is folk medicine called as SARAKACHI in Okinawa prefecture, Japan and is a traditional folk medicine of India exhibiting tonic, stimulation and antipyretic action. The supercritical carbon dioxide used in the present process is carbon dioxide of supercritical state exceeding the critical point in a phase equilibrium diagram. The extraction of the component and the removal of the extraction solvent after the extraction can be carried out without applying thermal energy.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention is directed to the use of Sulkacheman [Rutaceae, Toddalia asiat.
ica (L,) Lam, CT.

aculeata I'ers, etc., and which, in the numerical extraction method, is a compound that has a functional group such as an epoxide ring in its molecular structure that is easily altered during the extraction process. Concerning how to extract single chicks.

More specifically, the present invention relates to a method of extracting organic compounds from a substance containing easily-denatured organic compounds without deterioration using supercritical carbon dioxide.

<Prior Art> The root of Sarcacheman has been known as a folk medicine in India for its tonic, stimulating, and antipyretic effects since ancient times.
In the Okinawa region, the root bark of this plant is called ``Sarakake'' and is used as a folk medicine.

Since the root bark is expected to exhibit useful pharmacological effects, many chemical studies have been conducted on the components contained in the root bark of Sarca chemican. The main component of the root bark was initially extracted from a methanol extract prepared by digesting the root bark of this plant in methanol, and its structural formula is todalolactone (toddalolactone), which is represented by the structural formula (I).
Actone).

Under these circumstances, researchers have since focused their research on the components contained in this plant, using the extract extracted according to the above method as the subject of research.
The research has been conducted using actone (I) as the main component.

However, later the xylem of this plant was extracted using diethyl ether as an extraction solvent, and todalolactone (tod
toddalolactone (I) instead of dalolactone (I)
Acreadin (
aculeatin) (II) was obtained, and in this report, todalolactone.

(toddalolactone) (1) was not obtained.

<Problem to be solved by the invention> As mentioned above, some of the components of medicinal plants known to date cannot be extracted by solvent extraction methods, which have been frequently used, and steam distillation methods. , necessarily under heat during extraction! Because of this, there are many cases in which the true active ingredients are not extracted, but instead are extracted that have undergone chemical changes such as hydrolysis, dehydration, polymerization, or air oxidation.

For this reason, there is a need for a method for appropriately extracting active ingredients from substances containing organic compounds that are susceptible to deterioration, without causing deterioration.

The purpose of the present invention is to solve the above-mentioned problems and provide a method for extracting organic compounds that are easily denatured by an extraction method using supercritical carbon dioxide without denaturing them and improving the extraction efficiency. try to.

Means for Solving the Problems> The present invention is an alteration method characterized by extracting the easily alterable organic compound from a substance containing the easily alterable organic compound without altering the substance using supercritical carbon dioxide. Provides an easy method for organic conversion and extraction of metal objects.

Here, it is preferable that the organic compound that is susceptible to deterioration is a natural organic compound having an epoxy ring in its structure, and that the step of extracting without deterioration is one that extracts while preserving the epoxy ring.

The present invention will be explained in detail below.

The supercritical carbon dioxide used in the extraction method of the present invention refers to carbon dioxide in a supercritical state exceeding the critical point in the phase diagram.

It is known that in a region exceeding the critical temperature (31.1° C.) and critical pressure (72.9 atmospheres), there is no distinction between liquid and gas, and the liquid becomes a single phase, exhibiting a unique dissolving power.

The present invention is characterized by using such supercritical carbon dioxide to extract organic compounds from a mixture containing organic compounds that are easily denatured without denaturing them.

The organic compound that is susceptible to deterioration may be of any kind and is not limited.

In particular, organic compounds having functional groups that are susceptible to hydrolysis, dehydration, polymerization, and oxidation reactions during extraction are preferred.

The temperature and pressure of the supercritical carbon dioxide used may be adjusted as appropriate depending on the type of organic compound to be extracted.

The use of supercritical carbon dioxide has the following advantages in contrast to solvent extraction and steam distillation, which are conventionally frequently used methods for extracting plant components.

(1) There is no need to apply thermal energy during extraction, +rI11 There is no need to apply thermal energy when removing the extraction solvent after extraction, +iii+ During extraction, the extract is dissolved in supercritical carbon dioxide, which is the extraction solvent. As a result of being shielded from the air, carbon dioxide itself is less susceptible to air oxidation than the alcohols, ketones, esters, and halogenated hydrocarbons that are most commonly used in solvent extraction methods. Since it has poor reactivity, it is unlikely to produce artificial products by reacting with extracts.

Since carbon dioxide itself is not toxic, there is no need to consider the toxicity of residual solvents when the extracted components are used as medicines.

In the present invention, an entrainer (third component as an extraction aid) may be used in combination with supercritical carbon dioxide, if necessary.

Examples of entrainers include solvents such as acetone, methyl ethyl ketone, methanol, ethanol, and n-hexane.

Next, the extraction method using supercritical carbon dioxide according to the present invention will be specifically explained with reference to FIG. 1, but the method of the present invention is not limited thereto.

FIG. 1 shows a circulation path that is equipped with an extraction tank 1 and a separation tank 5 that can be adjusted to a predetermined pressure and temperature, and that are connected by a conduit 16. A carbon supply source 9 and an entrenner storage tank 11 are provided, and carbon dioxide and entrenner are supplied into the circulation path, respectively, and the other recovery side path of the circulation path has a configuration in which the extraction tank 1 and the separation tank 5 are communicated.

The carbon dioxide supply source 9 is communicated from the separation tank 5 to the supply side circulation path via the pressure-resistant check valve 8, and further communicated to the extraction tank 1 via the boost pump 10 and the heat exchanger 15.

The entrainer storage tank 11 is communicated via a boost pump 13 and a stop valve 14 to a circulation path on the supply side between the boost pump 1° and the heat exchanger 15.

On the other hand, the extraction tank 1 is communicated with a separation tank 5 equipped with a recovery pipe 7 having a stop valve 6 at the lower end via a pressure reduction valve 2, a heat exchanger 3, and a stop valve 4, and this forms a circulation path on the recovery side. .

Below, we will explain the operation of the apparatus shown in Figure 1 by taking Sarka Chemical as an example of a substance containing the compound to be extracted, and by taking as an example a case where a compound having an epoxy ring as an organic compound that is easily altered in Sarka Chemical is extracted. do.

The extraction tank 1 is filled with Sarca chemicalan, preferably in a pulverized state. This extraction tank 1 can be adjusted to a predetermined pressure and temperature, and a conduit 16 is connected to the bottom of the extraction tank 1, from which supercritical carbon dioxide, meth, ethanol, acetone, etc. as an entrainer are supplied. Supercritical carbon dioxide containing supercritical carbon dioxide is introduced via a heat exchanger 15.

The entrainer is connected to the conduit 12 from the entrainer storage tank 11.
, a boost pump 13 and a stop valve 14. Then, in this extraction WIl, the substance containing the compound to be extracted is brought into contact with supercritical carbon dioxide (hereinafter referred to simply as the extractant) containing the entrenerator, and the supercritical carbon dioxide is mixed into the extractant. Extract compounds with epoxy rings.

Next, the extractant containing the epoxy ring-containing compound dissolved therein is drawn out from the upper part of the extraction tank 1, reduced in pressure with a pressure reducing valve 2, and then introduced into a separation tank 5 via a heat exchanger 3 and a stop valve 4.

In the separation tank 5, the extractant and carbon dioxide are separated by lowering the pressure and/or increasing the temperature, and the carbon dioxide is recovered from the conduit 16 via the pressure-resistant check valve 8 into the circulation path.

A compound having an epoxy ring, or if an entrenner is used, an entrenner and a compound having an epoxy ring are recovered from the recovery pipe 7 via the stop valve 6.

When the entrenner is collected and used for circulation, a second branch tank (not shown) is provided between the entrenner storage tank 11 and the communicating conduit 12 via the stop valve 6, and the epoxy ring is removed from the entrenner. It is preferable to separate and take out the compound having a .

On the other hand, the separated carbon dioxide is recovered to the supply side circulation path through the pressure-resistant check valve 8, and after being pressurized by the boost pump 10 and the heat exchanger 15 to become a supercritical fluid again, it is passed through the circulation path through the conduit 16. is recirculated to If some of the carbon dioxide to be circulated is lost, carbon dioxide is replenished from the carbon dioxide supply source 9.

In this way, epoxy compounds are extracted from Sarka Chemical with supercritical carbon dioxide, or after extraction with supercritical carbon dioxide, they are extracted with supercritical carbon dioxide in which an entrainer, preferably acetone, hexane, or methanol, etc. coexists. do. The following extraction conditions are preferably used.

Extraction pressure is preferably 80 to 400Kgf/cTr1
' gauge, more preferably 120 to 300 kgf/bagage, and the extraction temperature is preferably 35 to 100°C, more preferably 35 to 60°C.

Preferred examples of the entrainer include acetone, methyl ethyl ketone, methanol, ethanol, and n-hexane. These solvents as entrainers are usually present in the extractant at a concentration of 0.5 to 20 mo 1%,
More preferably, it is contained in an amount of 3 to 1%.

The solvent as an entrainer is removed from the extract, for example by vacuum drying.

By extracting with supercritical carbon dioxide as described above, it is possible to achieve a significant improvement in extraction efficiency in the field of lizard trees without deteriorating compounds that are easily susceptible to chemical deterioration.

<Examples> The present invention will be specifically described below with reference to Examples, but the present invention is not limited thereto.

(Example) Using the apparatus shown in FIG. 1, 21.6 g of crushed root bark of Sarca chemical was filled into extraction tank 1. As the extractant, only supercritical carbon dioxide was used, and the extraction pressure was 120 gf/cnf, 200 Kgf as shown in Table 1.
/c+f, increase sequentially to 300 Kgf/crIf, 7 each
The mixture was extracted for 8 hours, 2.5 hours, until almost no pale yellow viscous solid was observed (Experiment No. 1).

Next, acetone was added as an entrainer to supercritical carbon dioxide, and extraction was further performed for 7 hours. Extraction pressure is 2
00 Kgf/cnf (experiment number 2).

Subsequently, methanol was added to the supercritical carbon dioxide as an entrainer, and the extraction pressure was increased to 200 g f / crrf.
, 7 hours, and 300 Kgf/cnf for 5 hours (Experiment No. 3).

Table 1 shows the extraction conditions, extraction amount, and solubility in these extractions.

In addition, in Table 1, solubility has the following meanings.

Solubility (mg/Nu) In the extraction operation, the weight of the raw materials and the weight of the extract were determined by weighing with a balance, and the weight of the extract when using an entrenner was determined by weighing the extract after drying under reduced pressure.
Further, the amount of carbon dioxide was measured using a wet gas meter.

The extracts of experiments 1.2 and 3 obtained through the above series of operations were repeatedly separated by column chromatography using silica gel and recrystallization, respectively, and aculeatin (II), todalolactone
(todalolactone) (I), and 6-(3-chloro-2-hydroxy-3-methylbutyl)-5,7-simethoxycoumarin (
IV) was obtained. The yield of each component is shown in Table 2 (experiment number 1~
3).

(IV) Note that the yield as used in the present invention has the following meanings.

Yield (%) x 100 Table 1 By further examining the results of the above examples and the following comparative examples, the present inventor discovered the following fact.

Research on the root bark of Okinawan dust revealed that the main component present in the plant is toddalolactone.
one) (1), but aculeatin (acule
atin) (II).

Todalolactone (todd
alolactone) (1), organic acids contained in plants are eluted together with methanol extraction,
As a result of the acidity of the solvent during extraction, acreatin (
It was confirmed that this was due to the ring opening of the epoxy ring of aculeatin (II) to generate glycol.

At the same time, todalolactone methyl ether (toddal
olactone methylether) The following formula (
III) is also an artificial product produced by the action of methanol, which was used as a nucleophilic reagent, when the epoxy ring was cleaved by the same mechanism when methanol was used as a solvent. confirmed.

(III) (Comparative Example) (1) Conventional method As shown in the flowchart of FIG. 2, the root bark of Sarkachem mandarin (2) was cut into small pieces, and methanol (2) was added thereto and digested for 8 hours. After cooling, the methanol extract was collected by filtration, and methanol was newly added to the remaining root bark and digested for 8 hours, and the methanol extract was collected by filtration again. After repeating this operation, the methanol extract was collected and the methanol was distilled off under reduced pressure to produce methanol extract ①.

The methanol extract (2) produced by the above method was separated into a soluble part (base component-containing part) (2) and an insoluble part (2) in a 5% acetic acid aqueous solution. After making the 5% acetic acid soluble part ammonia alkaline and extracting it with chloroform, the chloroform solution was extracted with a 5% aqueous solution of sodium hydroxide to separate the phenolic base-containing part (5% aqueous sodium hydroxide solution) and the non-phenolic part. The base-containing part (chloroform m?7Ii) was separated into two parts.

A 5% aqueous solution (■) of sodium hydroxide containing a phenolic base was made acidic with hydrochloric acid, then made alkaline with ammonia, and extracted with chloroform. After drying the obtained chloroform extract over anhydrous magnesium sulfate, the solvent was distilled off to obtain the phenolic base part (2).

The chloroform solution (2), which is the non-phenolic base-containing part, was directly dried over anhydrous potassium carbonate, and the solvent was distilled off to obtain the non-phenolic base part (2).

Separately, the part (■) of the methanol extract that is insoluble in a 5% acetic acid aqueous solution is dissolved in a small amount of chloroform/methanol mixture.
After thoroughly air-drying, the mixture was extracted with hexane and then benzene using a Soxhlet extractor, and the respective solvents were distilled off to obtain a hexane-eluted phase [phase] and a benzene-eluted phase of 0. Ta.

The obtained four fractions (1), (2), [phase], and (2) were isolated into each component by repeating column chromatography using silica gel and recrystallization, and toddalolactone (1) was obtained. , toddalolactone methyl ether (toddalolactone methyl ether)
methylether) (Tlr) and 6
-(3-chloro-2-hydroxy-3-methylbutyl)
Three types of coumarins, -5,7-simethoxycoumarin (IV), were obtained. The above (I) and (II) obtained from each fraction
Table 2 (experiment number 4) shows the total yield of each of the three types of coumarins, I) and (rV). The four crude fractions from which the coumarin was isolated were assayed using thin layer chromatography, but aculeatin was not detected.
(II) was not detected at all.

(2) Soxhlet extraction method←() The root bark of Sarcachem mandarin was cut into small pieces and extracted using a Soxhlet extractor using methanol as a solvent. The solvent was distilled off from the methanol extract under reduced pressure to obtain a residue. The obtained residue was immediately subjected to column chromatography using silica gel and repeated recrystallization operations without using any separation method based on the chemical properties of organic compounds to obtain aculeatin (II),
toddalolactone (
I),)-darolactone methyl ether (todd
alolactonemethylether) (I
II), and 6-(3-chloro-2-hydroxy-3-methylbutyl)-5,7-simethoxycoumarin (
rv) was isolated. The total yield of each of these four types of coumarins is shown in Table 2 (Experiment No. 5).

Soxhlet extraction method using the above methanol as a solvent (
Comparing the results of Experiment No. 5) with the results of the conventional method (Experiment No. 4), although both use methanol as the extraction solvent, in the conventional method, todalolactone (todd
alolactone) (I) as the main component,
No aculeatin (II) was obtained.

On the other hand, in the Soxhlet extraction method, although toddalolactone (1) is obtained as the main component, acreatin (
If ) has also been obtained in reasonable yields.

This fact suggests that acreatine (II) was decomposed to produce todalolactone (I) during the conventional separation of methanol extracts based on their chemical properties. .

(3) Soxhlet extraction method→i11 The root bark of Sulcachemis was cut into small pieces, and extracted using a Soxhlet extractor for 8 hours using n-hexane as a solvent (Experiment No. 6). Next, extraction was performed using ether (experiment number 7) and benzene (experiment number 8) for 8 hours each. The solvent was distilled off from each solvent extract individually, and the silica gel chromatography method and recrystallization method were repeated to extract acreatin (IX), todalolactone (■
), and 6-(3-chloro-2-hydroxy-3-
methylbutyl)-5゜7-simethoxycoumarin (IV
)of! # Released.

Table 2 shows the yield of each coumarin obtained from each solvent.
(Experiment numbers 6 to 8).

In addition, todalolactone methyl ether (III) obtained by the conventional method (experiment number 4) and the Soxhlet extraction method using methanol as the extraction solvent (experiment number 5) was obtained from any of the extraction solvents in experiment numbers 6 to 8. It was also not detected in the resulting extract.

The fact that todalolactone methyl ether (III) cannot be obtained when a solvent other than methanol is used for extraction is due to the fact that when this compound is extracted using methanol as a solvent, acreatin (II) is extracted during the extraction. It can be concluded that it was produced by reaction with the solvent methanol.

Generally, it is known that the epoxy ring in the structure of acreatine (TI) opens under acidic conditions to give an α-substituted alcohol that reacts with glycol or a nucleophile present in the solvent. It is known that Sarca chemicalan contains relatively many types of organic acids, so these acids are eluted during extraction, making the extract acidic and producing acreatin (II).
Todalolactone (I) whose epoxy ring has undergone hydrolysis
It is concluded that todalolactone methyl ether (Ill) was produced by reacting with the solvent methanol.

In addition, when calculating the sum of each of acreatin (II) and todalolactone (I) obtained by Soxhlet extraction method (experiment numbers 6 to 8) using hexane, ether, and benzene, it was found that methanol was used as the extraction solvent. Unlike the conventional method (experiment number 4) and the Soxhlet extraction method using methanol (experiment number 5), acreatin (II) was obtained as the main component, and when compared with the yield of todalolactone (I), The value is about 10 times lower than that of acreatin (experiment number 4) and the Soxhlet extraction method using methanol (experiment number 5).
It is clear that II) is transformed into todalolactone (I) and todalolactone methyl ether (Ill).

As mentioned above, in Experiment Nos. 4 to 8 of the comparative example, it was clearly shown that the main component of Sarkachemican was acreatine (II), but as shown in the example, the results of using supercritical carbon dioxide (Experiment numbers 1 to 3) compared to the extraction method shown in the comparative example, the main component acreatin (
II) shows very good extraction efficiency.

Furthermore, when comparing the results when methanol is used as an entrenerator (experiment number 3) with the results of the conventional method using methanol as a solvent (experiment number 4) and the Soxhlet extraction method using methanol (experiment number 5), it is found that In the two cases, todalolactone methyl ether (III) is produced by cleavage of the epoxy ring, but in supercritical carbon dioxide extraction, todalolactone methyl ether (III) is produced even when methanol is used as an entrenerator.
) was not obtained at all, confirming that the contained components could be extracted without cleaving the epoxy ring.

<Effects of the Invention> According to the method of the present invention, components that are susceptible to deterioration when extracted using commonly used solvent extraction methods, such as compounds that have an epoxy ring in their structure, can be extracted without deterioration. Moreover, the extraction efficiency can be significantly improved.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram showing an example of an apparatus for carrying out the extraction method of the present invention. FIG. 2 is a flowchart illustrating a conventional extraction method. Explanation of symbols 1... Extraction tank, 2... Pressure reducing valve, 3...
・Heat exchanger, 4...stop valve, 5...
minute tank, 7... Recovery pipe, 8... Pressure resistant check valve, 9... Carbon dioxide supply source, 10... Boosting pump, 11... Entrenor storage tank, 12... Conduit, 13 ...boost pump, 14
... stop valve, 15 ... heat exchanger, 16 ... conduit, 17 ...
Drain patent applicant PCC Technology Co., Ltd. FIG, 1 Figure 2 Conventional method ■ Root bark of Sarukacheman ■ Methanol base-containing part Base-containing part (5%; NaOH* solution) (Chloroform solution)
Base part Base part

Claims (2)

[Claims] (1) A method for extracting an organic compound that is easily altered, the method comprising extracting the easily altered organic compound from a substance containing the easily altered organic compound using supercritical carbon dioxide without altering the organic compound. (2) The organic compound that is susceptible to deterioration is a natural organic compound having an epoxy ring in its structure, and the step of extracting without deterioration involves extracting while preserving the epoxy ring. A method for extracting organic compounds that are susceptible to deterioration.