JPWO2007010838A1 - (-)-Method for producing alkaline earth metal salt of hydroxycitric acid - Google Patents

Abstract

The present invention relates to a novel process for producing an alkaline earth metal salt of (−)-hydroxycitric acid represented by the following general structural formula (1) (hereinafter referred to as “compound (1)”). . [Wherein M represents an alkaline earth metal. The present invention relates to a garcinia extract and an alkaline earth metal oxide or alkaline earth within a range of 0.5 times to less than 0.9 times in molar ratio to (-)-hydroxycitric acid contained in garcinia. The step of obtaining a precipitate produced by reacting a metal hydroxide or its hydroxide and preferably cooling, and reacting the obtained precipitate with an alkaline earth metal salt and a base, It is a manufacturing method of the compound (1) which has the process of acquiring 1).

Description

The present invention relates to an alkaline earth metal salt (hereinafter referred to as “compound (1)”) of (−)-hydroxycitric acid (hereinafter referred to as “HCA”) represented by the following general structural formula (1). Or it relates to a novel process for producing the hydrate.
[Wherein M represents an alkaline earth metal. ]

  For example, HCA is known as a substance that is abundant in the skin of Garcinia, and inhibits ATP citrate lyase, which is one of the enzymes on the pathway to synthesize fat from citric acid, and increases body fat mass. It is known that it is useful for the treatment of obesity because of its suppression (see, for example, Patent Document 1).

In general, HCA is described in Lewis, Y. et al. S. These methods can be obtained by extracting from the skin of Garcinia, and the salts thereof can be obtained from HCA by a conventional method (for example, Non-Patent Document 1, Non-Patent Document 2, Patent See reference 2.) HCA and its salts are described in Lewis, Y. et al. S. In addition to these methods, for example, it can be produced according to the methods described in Patent Documents 3, 4, 5, 6, and 7. However, in these methods, for example, it is difficult to remove impurities such as pectin and organic acids such as citric acid, malic acid, tartaric acid, and it is difficult to produce high-purity HCA and the like.
In particular, the calcium salt of HCA can be produced by reacting an excess amount of calcium hydroxide with a garcinia extract. At the same time, the pectin contained in the extract forms a hard gel with calcium hydroxide, and Since citric acid and maleic acid form a calcium salt that is sparingly soluble in water, it is difficult to obtain a high-purity product by a known production method.
U.S. Pat. No. 3,766,692 Indian Patent No. 160753 International Publication No. 99/03464 Pamphlet US Pat. No. 6,875,891 International Publication No. 2004/100682 Pamphlet US Pat. No. 6,160,172 European Patent No. 866137 “Phytochemistry”, 1965, vol. 4, p. 619-625 Lewis, Y. et al. S. Et al., “Methods In Enzymology”, 1969, 13, p. 613-617

An object of the present invention is mainly to provide a novel production method for obtaining a highly pure compound (1).
Here, “high purity” refers to 96% or more, preferably 98% or more, and more preferably 99% or more.

As a result of intensive studies, the present inventors have found a production method that can achieve the above object, and have completed the present invention. Fortunately, an alkaline earth metal salt (hereinafter referred to as “compound (2)”) of an lactone form of HCA represented by the following general structural formula (2), which is an intermediate of compound (1), or A production method for easily obtaining the hydrate with high purity was also found.
[Wherein, M is as defined above. ]

As this invention, the manufacturing method of compound (1) or its hydrate which has at least following process ae can be mentioned, for example.
Step a: Garcinia extract and alkaline earth metal oxide or alkaline earth metal hydroxide or hydration thereof in a molar ratio of 0.5 to 0.9 times the HCA contained in Garcinia A process of reacting with a product,
Step b: A step of precipitating the product by leaving or cooling the reaction solution of Step a,
Step c: a step of obtaining a precipitate,
Step d: a step of reacting the obtained precipitate with an alkaline earth metal salt or a hydrate thereof and a base,
Step e: A step of obtaining an alkaline earth metal salt of HCA or a hydrate thereof from the reaction solution of the reaction of Step d.

Moreover, the manufacturing method of compound (2) or its hydrate which has at least following process a'-c 'as this invention can be mentioned.
Step a ': Alkaline earth metal oxide or alkaline earth metal hydroxide or water thereof in a range of 0.5 times to less than 0.9 times in molar ratio with respect to HCA contained in Garcinia extract and Garcinia A process of reacting with a Japanese product,
Step b ′: the step of precipitating the product by leaving or cooling the reaction solution of step a ′,
Step c ′: a step of obtaining a precipitate and recrystallizing the obtained precipitate.

The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity. The chromatogram obtained by HPLC analysis is represented. In the figure, the vertical axis represents time (minutes) and the horizontal axis represents absorption intensity.

Hereinafter, the present invention will be described in detail.
I. Production of Compound (1) and its Hydrate (1) About Step a Garcinia extract is an extract containing a large amount of HCA. ) From the pericarp using water, alcohol or the like.
Garcinia extract contains, for example, polysaccharides such as pectin, and organic acids such as citric acid, malic acid, and tartaric acid, although the amount is very small. Even Garcinia extract containing such impurities can be used in the present invention.
Currently, Garcinia extract is marketed as an aqueous solution containing HCA in the range of 10% to 70% by weight. Examples of such commercially available products include Garcinia extract S (manufactured by Nippon Shinyaku Co., Ltd.), Garcitic Gold (registered trademark) (manufactured by Renaissance Herb (USA), Citrin (registered trademark) (manufactured by Sabinsa (USA)), Citrimax. (Registered trademark) (manufactured by Inter Health (USA)).
The concentration of HCA contained in the garcinia extract is suitably within the range of 5% to 90% by weight, preferably within the range of 7% to 80% by weight, more preferably 10% to 70% by weight. Is within the range. If necessary, water may be added to adjust the concentration of HCA contained in the Garcinia extract.

The reaction between garcinia extract and alkaline earth metal oxide or alkaline earth metal hydroxide or hydrate thereof is, for example, garcinia extract and alkaline earth metal oxide or alkaline earth metal hydroxide or hydrate thereof. Can be performed by heating and stirring the product in an aqueous solution. At that time, if necessary, an appropriate amount of activated carbon may be added.
Examples of the “alkaline earth metal oxide” include calcium oxide. Examples of “alkaline earth metal hydroxides or hydrates thereof” include calcium hydroxide or hydrates thereof. Among these, calcium hydroxide dihydrate is particularly preferable.

  The amount of the alkaline earth metal oxide or alkaline earth metal hydroxide or hydrate thereof is not particularly limited as long as the reaction solution does not show basicity. For example, the amount of HCA contained in the garcinia extract to be used is not limited. On the other hand, the molar ratio is suitably in the range of 0.5 times or more and less than 0.9 times, preferably 0.7 times or more and less than 0.9 times, more preferably 0.8 times or more and 0.8. Within a range of less than 9 times.

  The amount of activated carbon used varies depending on the Garcinia extract to be used, but is suitably in the range of 1 to 10% by weight, preferably 2 to 7% by weight based on the HCA contained in the Garcinia extract. It is in the range of wt%, more preferably in the range of 3 wt% to 4 wt%.

The reaction temperature varies depending on the concentration of HCA contained in the garcinia extract and the amount of alkaline earth metal oxide or alkaline earth metal hydroxide used, but it is usually within the range of 20 ° C to 100 ° C. Preferably it exists in the range of 40 to 95 degreeC, More preferably, it exists in the range of 60 to 90 degreeC.
The reaction time varies depending on the reaction temperature and the like, but is suitably in the range of 1 minute to 24 hours, preferably in the range of 5 minutes to 12 hours, and more preferably in the range of 10 minutes to 1 hour.

(2) Step b After the reaction in step a, this step can be carried out, for example, by leaving the reaction solution in step a as it is at room temperature. Moreover, it can implement also by cooling the reaction liquid of the process a, and it is more preferable to cool rather than leaving at normal temperature. The cooling temperature is usually in the range of −10 ° C. to 30 ° C., preferably in the range of −5 ° C. to 25 ° C., and more preferably in the range of 0 ° C. to 20 ° C. The cooling time is suitably in the range of 1 minute to 48 hours, preferably in the range of 10 minutes to 36 hours, and more preferably in the range of 20 minutes to 24 hours.

(3) About step c This step can be carried out by performing a filtration operation by a conventional method.
Precipitates that can be produced in this step c are substantially free of impurities such as pectin, which is a polysaccharide, such as citric acid, malic acid, and tartaric acid, which have been difficult to completely remove until now. Does not contain.

(4) About step d This step is performed by, for example, dissolving the precipitate obtained in step c by heating in water, adding an alkaline earth metal salt or hydrate thereof and a base, and stirring with heating. be able to. If necessary, a filtering operation can be performed after adding the alkaline earth metal salt.

The amount of water used is, for example, suitably in the range of 5 to 100 times by weight with respect to the precipitate, preferably in the range of 10 to 70 times, more preferably in the range of 20 to 40 times. Is within.
Examples of alkaline earth metal salts include calcium salts.
Examples of the “calcium salt” include calcium chloride, calcium sulfate, calcium carbonate, and calcium bromide. Of these, calcium chloride dihydrate is particularly preferred.
The amount of the alkaline earth metal salt or hydrate thereof used is, for example, suitably in the range of 0.40 times to 0.70 times in terms of molar ratio with respect to the precipitate, preferably 0.45 times to It is in the range of 0.65 times, more preferably in the range of 0.50 times to 0.60 times.
Examples of the “base” include amines such as aqueous ammonia, pyridine and trimethylamine.
The amount of base used is, for example, suitably in the range of 0.5 to 2.0 times in molar ratio to the precipitate, preferably in the range of 0.9 to 1.5 times, More preferably, it is in the range of 1.0 to 1.2 times.
The reaction temperature is usually within the range of 20 ° C to 100 ° C, preferably within the range of 30 ° C to 95 ° C, and more preferably within the range of 40 ° C to 90 ° C.
The reaction time varies depending on the reaction temperature and the like, but is suitably in the range of 1 minute to 12 hours, preferably in the range of 5 minutes to 7 hours, and more preferably in the range of 10 minutes to 2 hours.

(5) Step e Compound (1) in the reaction solution of step d can be obtained by performing a known solid-liquid separation operation. In performing the solid-liquid separation operation, the compound (1) can be washed with water. Examples of the solid-liquid separation operation include a filtration operation, a dehydration operation using a centrifuge, or a juicer.
If necessary, the compound (1) can be further purified. Specifically, for example, the purity can be further increased by adding 10 to 20 times by weight of water to the obtained compound (1) and stirring and performing the solid-liquid separation operation. If necessary, you may heat-stir within the range of 40 to 60 degreeC.

Since the compound (1) obtained by performing solid-liquid separation operation contains a large amount of water, it is preferable to perform drying operation.
Examples of the drying operation include drying under reduced pressure.
The decompression force is, for example, suitably in the range of 1.0 × 10 ⁻¹³ Pa to 1.0 × 10 ⁵ Pa, preferably in the range of 1.0 × 10 ⁻⁹ Pa to 1.0 × 10 ⁴ Pa, more preferably 1. It is in the range of 0 × 10 ⁻⁵ Pa to 1.0 × 10 ³ Pa.
The drying temperature is, for example, suitably within the range of 50 ° C to 140 ° C, preferably within the range of 60 ° C to 130 ° C, and more preferably within the range of 70 ° C to 120 ° C.
The drying time is suitably in the range of 1 hour to 96 hours, preferably in the range of 12 hours to 72 hours, and more preferably in the range of 24 hours to 48 hours.

For the production of compound (1), the precipitate produced in step c from which impurities such as citric acid, malic acid, tartaric acid, etc., which are organic acids, such as pectin, which is a polysaccharide, is removed is easily used. A highly pure compound (1) can be obtained.
In addition, the compound (1) produced in the present invention uses only water as a reaction solvent and a washing solvent used in the production process, methanol, ethanol, butanol, chloroform, methylene chloride, acetonitrile, dimethylformamide, Since organic solvents such as acetone and dimethyl sulfoxide are not used, there is no concern about residual solvents harmful to humans and animals.

II. Compound (2) and production method thereof (1) Step a ′ This step is the same as Step a in I above.
(2) Step b ′ This step is the same as the step b of I described above.
(3) About Step c ′ This step can be carried out by recrystallizing the precipitate after obtaining the precipitate by performing a filtration operation by a conventional method.
To the obtained precipitate, for example, water in the range of 1 to 10 times by weight is added and heated in the range of 50 ° C. to 100 ° C. to dissolve the precipitate, and it is left as it is at room temperature or cooled. The compound (2) can be produced by recrystallization. The cooling temperature is usually in the range of −10 ° C. to 30 ° C., preferably in the range of −5 ° C. to 25 ° C., and more preferably in the range of 0 ° C. to 20 ° C. The cooling time is suitably in the range of 1 minute to 48 hours, preferably in the range of 10 minutes to 36 hours, and more preferably in the range of 20 minutes to 24 hours.

The compound (2) that can be produced in this step is substantially free of impurities such as pectin, which is a polysaccharide, such as citric acid, malic acid, and tartaric acid, which have been difficult to completely remove until now. Not contained in.
In addition, the compound (2) produced in the present invention uses only water as a reaction solvent and a washing solvent used in the production process, methanol, ethanol, butanol, chloroform, methylene chloride, acetonitrile, dimethylformamide, Since organic solvents such as acetone and dimethyl sulfoxide are not used, there is no concern about residual solvents harmful to humans and animals.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example 1
30 g of water was added to 20 g of Garcinia extract (Gartricic Gold (registered trademark) Liquid; manufactured by Renaissance Herb Inc. (USA); containing 60.75 wt% as HCA) while stirring, 3.03 g, 3.46 g, 3. 89 g, 4.33 g or 4.76 g of calcium hydroxide was added, and each reaction solution stirred at 85 ° C. for 30 minutes was allowed to stand at 5 ° C. for 2 days, and the resulting precipitate was collected by filtration.
The results are shown in Table 1.
The purity of the precipitate deposited under each condition was confirmed using a high performance liquid chromatography (hereinafter referred to as “HPLC”) apparatus.
0.1 g of the precipitate deposited under each condition was diluted with water so that the total amount became 100 mL, and HPLC measurement was performed under the following conditions.
[Measurement condition]
HPLC apparatus: liquid feeding unit: LC-7A (manufactured by Shimadzu Corporation)
Detector: SPD-10AV (manufactured by Shimadzu Corporation)
Column for organic acid analysis: ULTRON PS-80H
<8mmφx30cm> 1 piece (manufactured by Shinwa Kako Co., Ltd.)
<8mmφx5cm> 1 piece (Shinwa Kako Co., Ltd.)
Column temperature: 50 ° C
Mobile phase: water (adjusted to pH 2.20 using perchloric acid)
Flow rate: 0.81 ml / min UV-visible spectrometer Detection wavelength: 210 nm
Injection volume: 20 μl

The results are shown in FIGS.
1 to 8, peak 1 represents impurities contained in the mobile phase, peak 2 represents HCA lactone, peak 3 represents HCA, and peak 4 represents citric acid, an organic acid.
As a result of HPLC analysis of only the mobile phase used in Example 1, a chromatogram as shown in FIG. 1 was obtained.
As a result of HPLC analysis of the garcinia extract used in Example 1, a chromatogram as shown in FIG. 2 was obtained. The Garcinia extract was confirmed to contain at least citric acid (a substance having a retention time of about 8 minutes) as an impurity.
FIG. 5 shows the results when calcium hydroxide having a molar ratio of 0.9 times that of HCA contained in the Garcinia extract used in Example 1 is used. FIG. 5 shows the HCA contained in the Garcinia extract used in Example 1. FIG. 6 shows the results when calcium hydroxide having an equal molar ratio is used. In the precipitate obtained when calcium hydroxide having a molar ratio of 0.9 times and equal to that of HCA contained in the Garcinia extract used in Example 1 was used, the precipitate was obtained with citric acid (FIG. 5). , 6 was confirmed to contain a peak 4).
FIG. 3 shows the results obtained when calcium hydroxide having a molar ratio of 0.7 times the HCA contained in the Garcinia extract used in Example 1 is used. The results for the HCA contained in the Garcinia extract used in Example 1 are shown in FIG. FIG. 4 shows the results when calcium hydroxide having a molar ratio of 0.8 is used. The precipitate obtained when calcium hydroxide having a molar ratio of 0.8 times or less with respect to the HCA contained in the Garcinia extract used in Example 1 has been difficult to remove completely so far. It was also confirmed that impurities such as pectin, which is a polysaccharide, and organic acids such as citric acid, malic acid, and tartaric acid were not included.
Furthermore, 10 mL of water was added to each precipitate obtained when calcium hydroxide having a molar ratio of 0.7 times and 0.8 times that of HCA contained in the Garcinia extract used in Example 1 was used. The precipitate obtained after being dissolved by heating at 90 ° C. was subjected to HPLC measurement and measurement of the amount of calcium contained in the precipitate. The amount of calcium contained in the precipitate was measured according to a known method using a 0.05 M aqueous solution of ethylenediaminetetraacetic acid. It was confirmed that the recrystallized precipitates were only HCA lactone calcium salt (peak 2 in FIGS. 7 and 8) (see FIGS. 7 and 8).

Example 2
To 4 kg of Garcinia extract (Gartricic Gold (registered trademark) Liquid; manufactured by Renaissance Herb Co. (USA); containing 64.0% by weight as HCA), 6 L of water was added and stirred, and 0.64 kg of calcium hydroxide (8 .64 mol; 0.70-fold molar ratio of calcium hydroxide to HCA) and 100 g of activated carbon were added and stirred at 85 ° C. for 30 minutes. Thereafter, the reaction mixture was filtered while being washed with hot water at 80 ° C.
The filtrate was allowed to stand at 5 ° C. overnight, and 1.5 kg of the deposited precipitate (HCA lactone calcium salt) was collected by filtration.
7.7 L of water was added to the obtained calcium salt of the lactone form of HCA, dissolved at 90 ° C. with heating, stirred as it was for 5 minutes, and then filtered. The obtained filtrate was heated again to 85 ° C., cooled to 20 ° C. or less, and allowed to stand for 30 minutes. The resulting precipitate was collected by filtration to obtain 1.0 kg of purified calcium salt of HCA lactone. (Yield: 51%).
The amount of calcium contained in the precipitate was measured according to a known method using a 0.05 M aqueous solution of ethylenediaminetetraacetic acid.
Melting point: elemental analysis value (as C ₆ H ₄ O ₇ Ca · 4H ₂ O) over 250 ° C.
Theoretical value: H: 4.03%, C: 24.0%
Actual value: H: 3.88%, C: 23.9%
Calcium content:
Theoretical value: Ca: 13.35%
Actual value: Ca: 13.40%
Specific rotation: [α] _D ²⁰ = 67.0 ° (c = 0.2, H ₂ O)
¹ H NMR (D ₂ O)
4.84 (s, 1H), 3.18 (d, 1H), 2.83 (d, 1H)

Example 3 Production of Calcium Salt of HCA 20 L of water was added to 1.0 kg (4.4 mol) of the calcium salt of lactone form of HCA obtained in Example 2, and the mixture was heated and stirred at 80 ° C. for 5 minutes. Thereafter, 0.35 kg of calcium chloride dihydrate (2.4 mol) and 0.5 L of water were added and dissolved, and then the reaction solution was filtered. The obtained filtrate was again heated to 80 ° C., stirred as it was for 5 minutes, and then cooled to 50 ° C. to 60 ° C. To the reaction solution, 0.29 kg of 28% aqueous ammonia was added dropwise and stirred at 85 ° C. for 60 minutes, and then the resulting precipitate was subjected to solid-liquid separation with a centrifuge (manufactured by Sakuma Seisakusho) for 10 minutes. The resulting solid was collected to obtain 0.55 kg of crude HCA calcium salt.
8.25 L of water was added to the obtained crude calcium salt of HCA, heated to 50 ° C. and stirred for 5 minutes, and then subjected to solid-liquid separation with a centrifuge for 10 minutes. The obtained solid was collected and subjected to the same purification operation once more. After the obtained solid was dried at 100 ° C. for 1 hour, the solid was pulverized and then dried at 80 ° C. for 41 hours and 115 ° C. for 7 hours to obtain 0.62 kg of the target compound (yield: 53%).
Mp: 250 ° C. or higher Elemental analysis _{(as C 12 H 10 O 16 Ca 3} · 5H 2 O)
Theoretical value: H: 3.25%, C: 23.23%
Actual value: H: 3.40%, C: 23.11%
Calcium content:
Theoretical value: Ca: 19.38%
Actual value: Ca: 19.60%
Specific rotation: [α] _D ²⁰ = −26.0 ° (c = 0.2, H ₂ O)
¹ H NMR (D ₂ O)
4.11 (s, 2H), 2.84 (d, 2H), 2.64 (d, 2H)

  Since no organic solvent is used in the production process of compound (1), compound (1) can be produced safely and at low cost, and there is no concern about residual organic solvent. In addition, since a precipitate from which impurities such as citric acid, malic acid, and tartaric acid, which are organic acids, are removed, such as pectin, which is a polysaccharide contained in Garcinia extract, is obtained, high-purity compound (1) is obtained. Can be manufactured.

Claims (11)

A method for producing an alkaline earth metal salt of (−)-hydroxycitric acid represented by the following general structural formula (1) or a hydrate thereof, comprising at least the following steps a to e.
[Wherein M represents an alkaline earth metal. ]
Step a: Garcinia extract and alkaline earth metal oxide or alkaline earth metal within a range of 0.5 times to less than 0.9 times in molar ratio to (-)-hydroxycitric acid contained in Garcinia extract Reacting with a hydroxide or a hydrate thereof,
Step b: A step of precipitating the product by leaving or cooling the reaction solution of Step a,
Step c: a step of obtaining a precipitate,
Step d: a step of reacting the obtained precipitate with an alkaline earth metal salt or a hydrate thereof and a base,
Step e: A step of obtaining an alkaline earth metal salt of (−)-hydroxycitric acid or a hydrate thereof from the reaction solution of the reaction of Step d. The alkaline earth of (-)-hydroxycitric acid according to claim 1, wherein the garcinia extract is obtained by extracting from pericarp of Goraka (Garcinia cambogia), Indian mangosteen (Garcinia indica) or Gurgur (Garcinia atroviridis). A method for producing a metal salt or a hydrate thereof. The method for producing an alkaline earth metal salt of (−)-hydroxycitric acid or a hydrate thereof according to claim 1, wherein the base used in step d is aqueous ammonia, pyridine or trimethylamine. The method for producing an alkaline earth metal salt of (−)-hydroxycitric acid or a hydrate thereof according to claim 1, wherein the alkaline earth metal oxide used in step a is calcium oxide. The alkaline earth of (-)-hydroxycitric acid according to any one of claims 1 to 3, wherein the alkaline earth metal hydroxide or hydrate thereof used in step a is calcium hydroxide or a hydrate thereof. A method for producing a metal salt or a hydrate thereof. The alkaline earth metal salt of (−)-hydroxycitric acid according to claim 1, wherein the alkaline earth metal salt or hydrate thereof used in step d is a calcium salt or a hydrate thereof. Or the manufacturing method of the hydrate. The method for producing an alkaline earth metal salt of (−)-hydroxycitric acid or a hydrate thereof according to claim 6, wherein the calcium salt is calcium chloride. A process for producing an alkaline earth metal salt of a lactone form of (−)-hydroxycitric acid represented by the following general structural formula (2) or a hydrate thereof, having at least the following steps a ′ to c ′.
[Wherein M represents an alkaline earth metal. ]
Step a ': Alkaline earth metal oxide or alkaline earth within a range of 0.5 times to less than 0.9 times in molar ratio to Garcinia extract and (-)-hydroxycitric acid contained in Garcinia extract Reacting with a metal hydroxide or a hydrate thereof,
Step b ′: the step of precipitating the product by leaving or cooling the reaction solution of step a ′,
Step c ′: a step of obtaining a precipitate and recrystallizing the obtained precipitate. The lactone body of (-)-hydroxycitric acid according to claim 8, wherein the garcinia extract is obtained by extraction from pericarp of Goraka (Garcinia cambogia), Indian mangosteen (Garcinia indica), or Gurgl (Garcinia atroviridis). A method for producing an alkaline earth metal salt or a hydrate thereof. The alkaline earth metal salt or hydrate of the lactone form of (-)-hydroxycitric acid according to claim 8 or 9, wherein the alkaline earth metal oxide used in step a 'is calcium oxide. Manufacturing method. The lactone of (-)-hydroxycitric acid according to claim 8 or 9, wherein the alkaline earth metal hydroxide or hydrate thereof used in step a 'is calcium hydroxide or hydrate thereof. A method for producing an alkaline earth metal salt or hydrate thereof.