JP2975705B2 - Steroid derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the formula (1)

[0002]

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In the formula, R represents a hydrogen atom or a protecting group for a hydroxyl group, and Y represents

[0004]

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The present invention relates to a steroid derivative represented by

The steroid derivative represented by the above formula (1) produced by the present invention is known to be effective as a bone metabolism regulator and a therapeutic agent for hypercalcemia, and it is known that the steroid derivative is a 24,25-dihydroxycholecalcifie. Useful as an intermediate for the synthesis of rolls.

[0007]

2. Description of the Related Art Heretofore, as a method for producing 24,25-dihydroxycholecalciferol, a method using stigmasterol as a starting material (Japanese Patent Application Laid-Open No.
JP-A-108960), a method using colenic acid-3β-ol as a starting material (JP-A-54-36249).
JP, JP-A-55-73700, JP-A-55-73700
167299, JP-A-55-131000, JP-A-56-22763, and JP-A-56-22763.
No. 34665) is known.

[0008]

As described above, 24,
Although several methods for producing 25-dihydroxycholecalciferol are known, in producing 24,25-dihydroxycholecalciferol, a compound that can be used as a synthetic intermediate is selected from many compounds. It is preferable that the production process can be appropriately changed according to the raw material situation.

Therefore, an object of the present invention is to provide
An object of the present invention is to provide a compound useful as a synthetic intermediate of dihydroxycholecalciferol.

[0010]

According to the present invention, the above-mentioned object is achieved by providing a steroid derivative represented by the above formula (1).

The hydroxyl-protecting group which can be represented by R in the above formula (1) can be any commonly used protecting group as long as the purpose of the hydroxyl-protecting group is achieved. Has an acetyl group, a propionyl group,
Acyl groups such as butyryl group, isobutyryl group, valeryl group, isovaleryl group, 4-methylvaleryl group, pivaloyl group, benzoyl group, monochloroacetyl group, trifluoroacetyl group; methoxycarbonyl group, ethoxycarbonyl group, isopropoxycarbonyl group, Ali Alkoxycarbonyl groups such as roxycarbonyl group, benzyloxycarbonyl group, p-nitrobenzyloxycarbonyl group, p-methoxybenzyloxycarbonyl group, and phenoxycarbonyl group; trimethylsilyl group, triethylsilyl group,
Tri-substituted silyl groups such as triisopropylsilyl group, tert-butyldimethylsilyl group and tert-butyldiphenylsilyl group; methoxymethyl group, methoxyethoxymethyl group, 1- (ethoxy) ethyl group, methoxyisopropyl group, tetrahydrofuranyl group And an alkoxymethyl group which may have a substituent such as a tetrahydropyranyl group.

The steroid derivative represented by the formula (1) is
For example, it can be manufactured by the method described below.

First, the method of Ikegawa et al. (JP-A-54-128)
557) can be produced according to the formula (2)

[0014]

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In the formula, R ¹ represents a hydrogen atom or a protecting group for a hydroxyl group, and R ² represents a lower alkyl group.

[0016]

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In the formula, R ³ represents a hydrogen atom or a protecting group for a hydroxyl group to produce a steroid derivative represented by the formula:

The reducing agent which can be used for the reduction of the compound of the above formula (2) includes those usually used when converting an ester to an alcohol, and specifically includes, for example, aluminum hydride, hydride Examples thereof include aluminum lithium, diisobutylaluminum hydride, lithium trimethoxyaluminum hydride, and sodium borohydride. The amount of these reducing agents used varies depending on the reducing agent used, but is usually in the range of 0.5 to 200 moles per 1 mole of the steroid derivative of the formula (2). This reaction can be carried out in the presence of a catalyst such as aluminum chloride, ethanedithiol, and boron fluoride. Although the amount of the catalyst is not particularly limited, it can be generally in the range of 0.05 to 1 mol per 1 mol of the steroid derivative of the formula (2). The reaction is preferably performed in a solvent, and as the solvent, a solvent that does not adversely affect the reaction is selected from tetrahydrofuran, diethyl ether, benzene, toluene, xylene, methanol, ethanol, or the like depending on the reducing agent. Can be.
Although the amount of the solvent used is not limited, it is usually convenient to use the solvent in an amount of about 5 to 200 times the weight of the steroid derivative of the formula (2). The reaction is usually about -100 ° C to 50 ° C
Performed at a temperature in the range of

The steroid derivative of formula (3) thus obtained can be isolated and purified from the reaction mixture in the same manner as used in the isolation and purification of organic compounds. For example, an ammonium chloride aqueous solution is added to the reaction mixture under ice-cooling, and the supernatant organic layer is dried and concentrated to obtain a crude product, or the reaction mixture is poured into ice water and extracted with an organic solvent such as diethyl ether. The extract is washed successively with an aqueous ammonium chloride solution, water and brine, dried and concentrated to obtain a crude product. The obtained crude product is purified by recrystallization, chromatography or the like to obtain a steroid derivative of the formula (3).

The steroid derivative of the formula (3) is subjected, if necessary, to a protection reaction of the hydroxyl group at the 3-position. The protection reaction can be carried out in the same manner as the usual hydroxyl group protection reaction. Subsequently, the steroid derivative of the formula (3) is subjected to an oxidation reaction and, if necessary, to a deprotection reaction of the hydroxyl group at the 3-position, whereby a compound of the formula (4)

[0021]

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In the formula, R ⁴ represents a hydrogen atom or a protecting group for a hydroxyl group.

From the steroid derivative of the formula (3), the compound of the formula (4)
Is converted to a steroid derivative by a method usually used for converting an alcohol to an aldehyde, for example, a method using dimethyl sulfoxide, manganese dioxide, chromic acids, 4-methylmorpholin-N-oxide or a metal salt. be able to. For example, a steroid derivative of the formula (3) can be converted to a steroid derivative of the formula (4) by reacting with 4-methylmorpholin-N-oxide and tetrapropylammonium parthenate. The amount of 4-methylmorpholin, N-oxide to be used can be usually within a range of 1 to 200 times mol per mol of the steroid derivative of the formula (3). The amount of tetrapropylammonium pearl thenate used as a catalyst is not particularly limited, but is usually in the range of 0.01 to 1 mol per 1 mol of the steroid derivative of the formula (3). This reaction can be carried out in the presence of molecular sieves (4A, powder). The amount of mole sieves used is
The weight can be usually about 1 to 10 times the weight of the steroid derivative of the formula (3). The reaction is preferably performed in a solvent, and a solvent that does not adversely affect the reaction, such as chloroform and methylene chloride, is used. The amount of the solvent to be used is not limited, but is usually in the range of about 5 to 200 times the weight of the steroid derivative of the formula (3).
The reaction is usually performed at a temperature in the range of about 10 to 50C.

The steroid derivative of the formula (4) thus obtained is isolated and purified from the reaction mixture, for example, as follows. The reaction mixture is filtered using celite and the resulting solution is concentrated under reduced pressure. The obtained crude product is purified by chromatography or the like to obtain a steroid derivative of the formula (4).

The steroid derivative of the formula (4) is reacted with an isopropenyl Grignard reagent to give Y

[0026]

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The steroid derivative of the formula (1) of the present invention, that is, the formula (1-1)

[0028]

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In the formula, R can lead to a steroid derivative having the above-mentioned meaning. Examples of the isopropenyl Grignard reagent that can be used include, for example, isopropenyl magnesium chloride, isopropenyl magnesium bromide, isopropenyl magnesium iodide, and the like. The amount of the isopropenyl Grignard reagent to be used can be usually within a range of about 1 to 100 moles per 1 mole of the steroid derivative of the formula (4). The reaction is usually performed under an inert gas atmosphere.
The reaction is preferably performed in a solvent, and examples of the solvent include tetrahydrofuran, dimethoxyethane, diethyl ether, dioxane, and a mixed solvent thereof. The amount of the solvent to be used is not limited, but it is usually appropriate to use the solvent in an amount of about 5 to 200 times the weight of the steroid derivative of the formula (4). The reaction is usually performed at a temperature in the range of about -80C to 50C.

The thus obtained steroid derivative of the formula (1-1) can be isolated and purified from the reaction mixture in the same manner as in the usual method for the isolation and purification of organic compounds. For example, the reaction mixture is poured into an aqueous ammonium chloride solution or water, diethyl ether,
Extract with an organic solvent such as methylene chloride and ethyl acetate. The extract is washed with brine, dried over sodium sulfate, and concentrated to obtain a crude product. By purifying the crude product by recrystallization, chromatography or the like, the compound represented by the formula (1)
24R-hydroxy form and 24S-hydroxy form of the steroid derivative of -1) can be isolated.

The resulting steroid derivative of the formula (1-1) can be subjected to a hydroxyl-protecting group exchange or deprotection reaction, if necessary. Exchange or deprotection of a hydroxyl-protecting group can be carried out by combining ordinary deprotection and protection of a hydroxyl group.

The steroid derivative of the formula (1-1) thus obtained is subjected to epoxidation, so that Y is

[0033]

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The steroid derivative of the formula (1) according to the present invention, ie, the formula (1-2)

[0035]

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In the formula, R can be derived to a steroid derivative having the above-mentioned meaning.

The epoxidation of the steroid derivative of the formula (1-1) can be carried out by a method usually used for converting olefin to epoxide, for example, hydrogen peroxide-metal catalyst, organic peracid, alkyl hydroperoxide-metal complex. It can be performed by a method using a catalyst or the like. For example, equation (1-1)
Are converted to vanadium (III) acetylacetonate, hexacarbonylmolybdenum, tri-t
By reacting an alkyl hydroperoxide such as t-butyl hydroperoxide in the presence of a metal complex catalyst such as -butoxyaluminum or tetraisopropoxytitanium, a steroid derivative of the formula (1-2) can be obtained. . The amount of the alkyl hydroperoxide to be used can be generally in the range of about 1 to 200 mol per 1 mol of the steroid derivative of the formula (1-1). The amount of the metal complex catalyst used is not particularly limited, but is usually about 0.1 to 1 mol of the steroid derivative of the formula (1-1).
A range from 01 to 5 moles is suitable. The reaction is preferably performed in a solvent. As the solvent, for example, a solvent that does not adversely affect the reaction, such as chloroform, methylene chloride, carbon tetrachloride, 1,2-dichloroethane, benzene, toluene, and xylene, is used. The amount of solvent used is not limited,
Usually about 5 to 2 with respect to the steroid derivative of the formula (1-1)
It is convenient to use within the range of 00 times weight. The reaction is usually performed at a temperature in the range of about -100C to 50C.

The chemical formula (1-2) thus obtained
Isolation and purification of the steroid derivative from the reaction mixture
It is carried out in the same manner as a method usually used in the isolation and purification of an organic compound. For example, adding water to the reaction mixture,
The extract is extracted with an organic solvent such as ethyl acetate, and the extract is washed sequentially with an aqueous thiosulfate solution, an aqueous sodium bicarbonate solution, water and brine, dried and concentrated to obtain a crude product. The obtained crude product is purified by recrystallization, chromatography or the like to obtain a steroid derivative of the formula (1-2).

The steroid derivative of the formula (1-2) thus produced can be obtained by, for example, a method shown in the following reaction formula A, which is useful as a bone metabolism regulator and a therapeutic agent for hypercalcemia. it can be induced to 24,25-dihydroxy cholecalciferol shift Errol represented by 7).

[0040]

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In the formula, R has the meaning described above.

The steroid derivative of the formula (1-2) is optionally subjected to a deprotection reaction to give the steroid derivative (1-2a)
Then, the epoxy ring is opened to obtain a provitamin D ₃ derivative (5). Provitamin D ₃ derivative obtained (5)
By irradiating the product with ultraviolet rays according to a known method, and then subjecting the product to thermal isomerization, 24,25-dihydroxycholecalciferol (7) can be obtained.

[0043]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

[0044]

Reference Example 1 In a nitrogen atmosphere, 533 mg of lithium aluminum hydride was suspended in 73.8 ml of tetrahydrofuran. 4.69 g of methyl 3β- (t-butyldimethylsilyloxy) -24,25,26,27-tetrakisnorcholest-5,7-diene-23-carboxylate was dissolved in 20 ml of tetrahydrofuran. The solution was added dropwise under ice-cooling, and the mixture was stirred for 20 minutes while cooling. 150 ml of diethyl ether was added, and an aqueous solution of sodium sulfate was added dropwise, followed by stirring at room temperature for 30 minutes. The resulting reaction mixture was filtered through celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and 3β
-(T-butyldimethylsilyloxy) -25,26,
2.6 g of 27-trisnorcholest-5,7-dien-24-ol were obtained.

[0045]

Reference Example 2 Under a nitrogen atmosphere, 652 mg of lithium aluminum hydride was suspended in 90 ml of tetrahydrofuran.
The resulting mixture was added to 3β-methoxymethoxy-24,2
A solution of 5.1 g of ethyl 5,26,27-tetrakisnorcholest-5,7-diene-23-carboxylate in 25 ml of tetrahydrofuran was added dropwise under ice-cooling, and the mixture was stirred for 20 minutes while cooling. 150 ml of diethyl ether was added, an aqueous solution of sodium sulfate was added dropwise, and the mixture was added at room temperature for 30 minutes.
Stirred for minutes. The resulting reaction mixture was filtered through celite,
Concentrated under reduced pressure. The residue was purified by silica gel column chromatography and 3β-methoxymethoxy-2
2.8 g of 5,26,27-trisnorcholest-5,7-dien-24-ol was obtained.

[0046]

Reference Example 3 3β- (t-butyldimethylsilyloxy) -25,26,27-trisnorcholest-5,7
2.6 g of dien-24-ol was dissolved in 26 ml of methylene chloride under an argon atmosphere, 970 mg of N-methylmorpholine-N-oxide and 3.25 g of molecular sieves (4A, powder) were added to the resulting solution, and the mixture was stirred at room temperature. And stirred. After stirring for 15 minutes, 100 mg of tetrapropyl ammonium parthenate was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered using celite and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography, and 3β- (t-butyldimethylsilyloxy) -2
2.25 g of 5,26,27-trisnorcholest-5,7-dien-24-al were obtained.

[0047]

Reference Example 4 3β-methoxymethoxy-25,26,2
1 g of 7-trisnorcholestole-5,7-dien-24-ol was dissolved in 10 ml of methylene chloride under an argon atmosphere, and 440 mg of N-methylmorpholine-N-oxide and molecular sieves (4A, powder ) And stirred at room temperature. After stirring for 15 minutes, 45 mg of tetrapropyl ammonium parthenate was added, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was filtered using celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and 3β-methoxymethoxy-25,26,27-trisnorcholestot-5,
835 mg of 7-dien-24-al are obtained.

[0048]

Reference Example 5 3β- (t-butyldimethylsilyloxy) -25,26,27-trisnorcholest-5,7
305 mg of -diene-24-al was dissolved in 10 ml of tetrahydrofuran, 1.5 ml of a tetrahydrofuran solution of tetrabutylammonium fluoride (1.0 mol / l) was added, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was poured into water and extracted with diethyl ether. The extract was washed with water and brine, dried, and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography,
188 mg of 3β-hydroxy-25,26,27-trisnorcholest-5,7-dien-24-al were obtained.

[0049]

Example 1 3β- (t-butyldimethylsilyloxy) -25,26,27-trisnorcholest-5,7
Dissolve 2.25 g of diene-24-al in 45 ml of dry tetrahydrofuran and add -60 g under argon atmosphere.
Stirred at ° C. 19 ml of isopropenylmagnesium bromide was added dropwise to the obtained solution,
Stirred for hours. An aqueous ammonium chloride solution was added to the reaction mixture, the mixture was returned to room temperature, and water and ethyl acetate were added for extraction. The extract was washed with aqueous sodium hydrogen carbonate, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and high performance liquid chromatography, and 3β- (t-butyldimethylsilyloxy) cholest 5,7,25-triene-
0.49 g of 24S-ol and 3β- (t-butyldimethylsilyloxy) cholest having the following physical property values:
0.56 g of 5,7,25-trien-24R-ol was obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.07 (s, 6H), 0.62 (s, 3H), 0.89 (s, 9H), 0.93 (s, 3H), 3.50 to 3.67 ( m, 1H), 3.95 to 4.09 (m, 1H), 4.83 (s, 1H), 4.93 (s, 1H), 5.38 (m, 1H), 5.54 (m, 1H)

[0051]

Example 2 3β-methoxymethoxy-25,26,2
1.1 g of 7-trisnorcholest-5,7-dien-24-al was dissolved in 25 ml of dry tetrahydrofuran and stirred at -60 ° C under an argon atmosphere. 11 ml of isopropenylmagnesium bromide was added dropwise to the resulting solution, and the mixture was stirred for 15 hours while cooling. An aqueous ammonium chloride solution was added to the reaction mixture, the mixture was returned to room temperature, and water and ethyl acetate were added for extraction. The aqueous extract is treated with aqueous sodium bicarbonate,
The extract was washed with water and saline, dried over sodium sulfate, and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography and high performance liquid chromatography, and 3β-methoxymethoxycholest 5,7,2
0.26 g of 5-trien-24S-ol and 3β-methoxymethoxycholest-5 having the following physical property values
0.25 g of 7,25-trien-24R-ol was obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.62 (s, 3H), 0.91 (s, 3H), 3.33 (s, 3H), 3.22 to 3.53 (m, 1H), 3.92 to 4.07 (m, 1H), 4.48 to 4.76 (m, 2H), 4.84 (s, 1H), 4.93 (s, 1H), 5.38 (m, 1H), 5.55 (m, 1H)

[0053]

Example 3 1 g of 3β-hydroxy-25,26,27-trisnorcholest-5,7-dien-24-al
Was dissolved in 26 ml of dry tetrahydrofuran and stirred at -60 ° C under an argon atmosphere. 23 ml of isopropenylmagnesium bromide was added dropwise to the obtained solution, and the mixture was stirred for 20 hours while cooling. An aqueous ammonium chloride solution was added to the reaction mixture, the mixture was returned to room temperature, and water and ethyl acetate were added for extraction. The extract was washed with aqueous sodium hydrogen carbonate, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and high performance liquid chromatography, and 0.17 g of cholest 5,7,25-trien-3β, 24S-ol and cholest-5 having the following physical property values were obtained.
7,25-triene-3β, 24R-diol 0.19
g was obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.63 (s, 3H), 0.91 (s, 3H), 3.57 to 3.66 (m, 1H), 3.91 to 4.07 (m, 1H), 4.83 (s, 1H), 4.92 (s, 1H), 5.38 (m, 1H), 5.56 (m, 1H)

[0055]

EXAMPLE 4 84.1 mg of 3, β- (t-butyldimethylsilyloxy) cholestol 5,7,25-trien-24R-ol was dissolved in 5 ml of toluene, 5 mg of vanadium (III) acetylacetonate and 5 mg of t-butylhydrogen were dissolved. Add 0.2 ml of peroxide (80%)
Stirred at room temperature for 1 hour. Water was added to the reaction mixture, and extracted with ethyl acetate. The extract was washed with an aqueous thiosulfate solution, an aqueous sodium bicarbonate solution, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography to obtain 3β- (t-butyldimethylsilyloxy) -2 having the following physical properties.
5,26-epoxycholest 5,7-diene-24R-
75.6 mg of all were obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.06 (s, 6H), 0.64 (s, 3H), 0.89 (s, 9H), 0.94 (s, 3H), 1.33 (s, 3H), 2.61 (d, 1H), 2.92 (d, 1H), 3.45 to 4.08 (m, 2H), 5.38 (m, 1H), 5.53 (m, 1H)

[0057]

Example 5 3β-methoxymethoxycholest-5
100 mg of 7,25-trien-24R-ol was dissolved in 7 ml of toluene, and 7 mg of vanadium (III) acetylacetonate and t-butyl hydroperoxide (8
(0%) was added and stirred at room temperature for 1 hour. Water was added to the reaction mixture, and extracted with ethyl acetate. The extract was washed with an aqueous thiosulfate solution, an aqueous sodium bicarbonate solution, water, and a saline solution,
After drying over sodium sulfate, it was concentrated under reduced pressure.
The residue was purified using silica gel column chromatography and had the following physical property values for 25,26-epoxy-3.
β-methoxymethoxycholest-5,7-diene-24
80.5 mg of R-ol were obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.63 (s, 3H), 0.92 (s, 3H), 1.34 (s, 3H), 2.60 (d, 1H), 2.91 (d, 1H), 3.33 (s, 3H), 3.25 to 4.09 (m, 2H), 4.48 to 4.77 (m, 2H), 5.38 (m, 1H), 5.54 (m, 1H)

[0059]

Embodiment 6 Cholest-5,7,25-triene-3
85.5 mg of β, 24R-diol was dissolved in 7 ml of toluene, and 7 mg of vanadium (III) acetylacetonate and 0.3% of t-butyl hydroperoxide (80%) were added.
ml was added and stirred at room temperature for 1 hour. Water was added to the reaction mixture, and extracted with ethyl acetate. The extract was washed with an aqueous thiosulfate solution, an aqueous sodium bicarbonate solution, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and had the following physical property values of 25,26-epoxycholest-5,7.
71.2 mg of -diene-3β, 24R-diol were obtained.

¹ H-NMR spectrum (90 MHz) CDCl ₃ , TMS, δ: 0.63 (s, 3H), 0.93 (s, 3H), 1.34 (s, 3H), 2.60 (d, 1H), 2.92 (d, 1H), 3.36 to 4.09 (m, 2H), 5.38 (m, 1H), 5.55 (m, 1H)

[0061]

Reference Example 6 Under a nitrogen atmosphere, 75.6 mg of 3β- (t-butyldimethylsilyloxy) -25,26-epoxycholest-5,7-dien-24R-ol was dissolved in 5 ml of dry tetrahydrofuran, and hydrogenated. 5 mg of aluminum lithium was added and the mixture was stirred at room temperature for 5 minutes. The reaction mixture was cooled on ice, 10 ml of diethyl ether was added,
The excess lithium aluminum hydride was then treated with aqueous sodium sulfate. The resulting mixture was filtered using celite and concentrated under reduced pressure. 3β- (t-butyldimethylsilyloxy) cholestot-5,7-diene-24
74.5 mg of R, 25-diol were obtained.

[0062]

Reference Example 7 Under a nitrogen atmosphere, 3β- (t-butyldimethylsilyloxy) cholest-5,7-diene-24R,
44.8 mg of 25-diol was dissolved in 5 ml of tetrahydrofuran, and tetrabutylammonium fluoride (1 mol /
l, tetrahydrofuran solution) at room temperature.
Stir for 5 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogen carbonate, water and brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification was performed using silica gel column chromatography to obtain 43.0 mg of cholest-5,7-diene-3β, 24R, 25-triol.

[0063]

Reference Example 8 Cholest-5,7-diene-3β, 24
43.0 mg of R, 25-triol in 300 ml of ethanol
, And the mixture was stirred under ice cooling with nitrogen. The resulting mixture was added to the mixture with a high pressure mercury lamp using a Vycor filter.
UV irradiation for a minute. The reaction mixture was allowed to stir for 2 hours and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and then high performance liquid chromatography to obtain 6.9 mg of 24R, 25-dihydroxycholecalciferol.

[0064]

According to the present invention, a steroid derivative represented by the formula (1) which can be easily derived into 24,25-dihydroxycholecalciferol can be industrially advantageously produced.

──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Manzo Shiono 2045 Sakura, Kurashiki City, Okayama Prefecture 1 Kuraray Co., Ltd. (58) Field surveyed (Int. Cl. ⁶ , DB name) C07J 9/00 C07J 17 / 00 A61K 31/575 ADF

Claims (1)

(57) [Claims] (1) Formula (1) In the formula, R represents a hydrogen atom or a protecting group for a hydroxyl group, and Y represents A steroid derivative represented by