JPH0489476A - Preparation of 25-hydroxy pre-vitamin d derivative - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 25-hydroxy previtamin D derivatives.

The 25-hydroxy previtamin D derivative provided by the present invention has been reported to increase bone mass and is expected to be used as a therapeutic agent for osteoporosis, etc. 24.25-
It is useful as a synthetic intermediate for 25-hydroxyvitamin D derivatives such as dihydroxyvitamin D3.

[Prior Art] Conventionally, vitamin DH conductors have been produced in many cases by irradiating the corresponding steroid-5,7-diene derivative with ultraviolet light to cleave its B ring (6Z
)-9,10-Secosteroid-5(10),6.8-
9. isomerizing the 1-reengineering derivative with thermal energy;
10-secosteroid-io (19), 5.7-1-
This is done by converting it into a diene derivative. This cleavage reaction of the B ring of the steroid-5,7-diene derivative by ultraviolet irradiation is an equilibrium reaction, and the desired (6Z
)-9,10-Secosteroid-5(10),6.8-
It is known that in order to increase the selectivity of triene derivatives, it is necessary to suppress the conversion rate of the corresponding steroid-5,7-diene derivatives. Therefore, when producing 25-hydroxyvitamin D derivatives industrially, it is necessary to combine the product 25-hydroxyvitamin D derivative or 25-hydroxyprevitamin D derivative with the corresponding steroid-5,7-diene derivative as the raw material. Separation becomes a problem.

Furthermore, the photocleavage reaction of 7-dihydrocholesterol using ultraviolet light of a specific wavelength (including ultraviolet laser light) is known;
Society (J, Am.

Chem, Soc,), Volume 103, Page 6781 (19
1981) and Vol. 104, p. 5780 (1982)], and there are no known examples of using ultraviolet laser light for the production of vitamin D derivatives having a hydroxyl group at the 25th position.

[Problem to be solved by the invention] Product 25-hydroxyvitamin D derivative or 2
Possible methods for separating the 5-hydroxyprevitamin derivative from the corresponding steroid-5,7-diene derivative as a raw material include chromatographic methods such as thin layer chromatography, column chromatography, and high-performance liquid chromatography, and recrystallization methods. However, since the products and raw materials are isomers with similar properties, the above separation method is not necessarily industrially satisfactory, especially when the desired product is not the main component in the reaction mixture. requires complicated steps to isolate and purify the product from the reaction mixture.

Therefore, the object of the present invention is to provide 25-hydroxy previtamin D which can be derived into 25-hydroxy vitamin D derivatives.
The object of the present invention is to provide a method for selectively producing derivatives with good yield.

[Means for Solving the Problems] According to the present invention, the above object is achieved by (1) - General formula I) (wherein R1 and R2 each represent a hydrogen atom or a hydroxyl group protecting group, and Xl is a hydrogen atom or represents a group represented by the formula -OR'', where X2 represents a hydrogen atom, or
25-hydroxy represented by Taxisterol derivative [hereinafter referred to as compound (I)]
25 represented by the general formula (II) (wherein, RI RZ -Hydroxyprevitamin DI! 25, which is hereinafter referred to as compound (II), is represented by the general formula I[+) (wherein RI RI X I X 2 and Y are each as defined above) -Hydroxyprovitamin D derivative [hereinafter referred to as compound (I[l)]
It is characterized by sequentially or simultaneously irradiating an ultraviolet laser beam having a wavelength selected from the range of 340 nm and an ultraviolet laser beam having a wavelength selected from the wavelength range of 280 to 400 nm and longer than the ultraviolet laser beam. and (2) obtain compound (1) by irradiating compound (I[1) with an ultraviolet laser beam having a wavelength selected from the wavelength range of 190 to 31' Onm, and (L has a wavelength of 280
This is achieved by providing a method for producing compound (I[), which is characterized by irradiating with ultraviolet laser light selected from the range of ~400 nm and having a longer wavelength than the above-mentioned ultraviolet laser light.

Examples of the protecting group for the hydroxyl group represented by RI R2, R3 and R4 in the above general formula include an acyl group, an alkoxycarbonyl group, a trisubstituted silyl group, an alkoxymethyl group which may have a substituent, etc. Any protecting group may be used as long as it functions as a protecting group for the hydroxyl group. Examples of the acyl group include lower alkanoyl groups such as acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, and pivaloyl group; benzoyl group , nitrobenzoyl group, dinitrobenzoyl group, allenoyl group such as trimethylbenzoyl group; methoxyacetyl group, phenoxyacetyl group, chloroacetyl group,
Examples include substituted acetyl groups such as dichloroacetyl group, trichloroacetyl group, and trifluoroacetyl group. Examples of the alkoxycarbonyl group include lower alkoxycarbonyl groups such as methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, and tert-butoxycarbonyl group, phenoxycarbonyl group, - Aretzky dicarbonyl groups such as methylphenoxycarbonyl group, p-nitrophenoxycarbonyl group, p-glolphenoxycarbonyl group, p-bromophenoxycarbonyl group, benzyloxycarbonyl group, p-bromobenzyloxycarbonyl group, p- Examples include aralkoxycarbonyl groups such as nitrobenzyloxycarbonyl groups; alkenyloxycarbonyl groups such as allyloxycarbonyl groups, methallyloxycarbonyl groups, and dimethylallyloxycarbonyl groups.

Examples of the trisubstituted silyl group include trimethylsilyl group,
triethylsilyl group, triisopropylsilyl group, te
Trialkylsilyl groups such as rt-butyldimethylsilyl group; alkyldiarylsilyl groups such as tert-butyldiphenylsilyl group; and the like. Examples of the alkoxymethyl group that may have a substituent include alkoxymethyl groups such as methoxymethyl group, methoxyethoxymethyl group, and benzyloxymethyl group, ethoxyethyl group, methoxyisopropyl group, and methoxy-4-tetrahydropyranyl group. Substituted alkoxymethyl groups such as groups;
Examples include offsacycloalkan-2-yl groups such as 2-tetrahydropyranyl group and 2-tetrahydrofuranyl group. Further, two of R2R3 and R4 may be combined to represent an alkylidene group such as a methylene group, an ethylidene group, an isopropylidene group, a benzylidene group, or a cyclohexylidene group.

By irradiating compound (I [ ), the compound (I) is exposed to ultraviolet laser light (hereinafter referred to as ultraviolet laser light ( B)
A reaction in which compound (I) is converted to compound (I[) by irradiation with ultraviolet laser light (A) and ultraviolet laser light (B) sequentially or The reaction of converting compound (I[l) into compound (I) by simultaneous irradiation is preferably carried out in a solvent. Examples of the solvent include hexane, heptane, cyclohexane, ligroin, benzene, toluene, xylene, etc. Hydrocarbon solvents such as nibrobenzene, chlorobenzene, carbon tetrachloride, 1,2-dichloroethane,
1. Halogenated hydrocarbon solvents such as 2-dibromoethane, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, and ethyl cellosolve; alcohol solvents such as methanol, ethanol, and propatool are used, and the amount used is as follows: It is usually 50 to 500,000 times the weight of the compound to be irradiated with ultraviolet laser light. These reactions are normally carried out at temperatures within the range of -50°C to 120°C, preferably within the range of -10°C to 20°C.

Irradiation with ultraviolet laser light (B) can also be performed in the presence of a sensitizer such as benzophenone, acetophenone, butyrophenone, 9-fluorenone, or xanthone. The amount of the sensitizer used is preferably in the range of about 0.05 to 50 mol per mol of the compound to be irradiated with the ultraviolet laser beam (B).

The ultraviolet laser light (A) has a wavelength of 220 to 295n.
It is preferable that the ultraviolet laser beam (B) has a wavelength selected from the range of 295 to 380 m.
It is preferable to have a wavelength selected from the nm range.
Examples of ultraviolet lasers that emit ultraviolet laser light (A) include argon ion laser, krypton fluoride excimer laser, argon fluoride excimer laser, krypton chloride excimer laser 1 xenon chloride excimer laser 1 dye laser, and YAG laser. - YAG laser-excited dye laser, excimer laser-excited dye laser, ruby laser, etc. are used, and ultraviolet laser light (B
Examples of the ultraviolet laser that oscillates include nitrogen laser, argon ion laser, krypton ion laser, helium-cadmium laser, xenon fluoride excimer laser, xenon chloride excimer laser, dye laser, YAG laser, YAG laser excited dye laser,
Excimer laser, excited dye laser, ruby laser, etc. are used.

The reaction mixture containing compound (I) obtained by irradiating compound (I) with ultraviolet laser light (A) can be directly subjected to the next reaction, but if compound (I) is It can also be subjected to the next reaction after isolation and purification in the same manner as the methods used in the isolation and purification of ordinary organic compounds. Isolation and purification of compound (I) from the reaction mixture is carried out, for example, by concentrating the reaction mixture under reduced pressure and then purifying the residue by recrystallization, chromatography, or the like.

Isolation and purification of the compound (n) obtained as described above from the reaction mixture is carried out in the same manner as the method used in the isolation and purification of ordinary organic compounds. For example, after concentrating the reaction mixture under reduced pressure, the residue is crystallized,
This is done by purifying by chromatography or the like. Furthermore, compound (It) can be subjected to the next reaction without being isolated or purified.

Compound (II) is subjected to an isomerization reaction using thermal energy, and then, if necessary, the product is subjected to a deprotection reaction of the hydroxyl group to form a compound of the general formula (IV) (wherein, X3 represents a hydrogen atom or a hydroxyl group). , and X4 represents a hydrogen atom,
or X3 and X4 together represent an oxo group, and Yl represents a hydrogen atom or a hydroxyl group) 25-hydroxyvitamin D derivative [hereinafter referred to as
This is called the compound (TV)].

The isomerization reaction by thermal energy is usually about 0 to 120℃
It is carried out at a temperature within the range of . This reaction is usually carried out in a solvent, and the solvent used is the above-mentioned compound (I[+
) to compound (I).

The deprotection reaction of the hydroxyl group, which is carried out as necessary, is carried out in the same manner as the method used in ordinary deprotection of the hydroxyl group.

The isolation and purification of compound (IV) thus obtained from the reaction mixture is carried out in the same manner as the method used in the isolation and purification of ordinary organic compounds. It is then extracted with an organic solvent such as diethyl ether, ethyl acetate, or methylene chloride, and if necessary, washed with dilute hydrochloric acid, dilute sulfuric acid, aqueous sodium bicarbonate, water, or saline to make it neutral. This is carried out by dehydrating using a desiccant such as, concentrating under reduced pressure, and purifying the residue by recrystallization, chromatography, etc.

[Examples] Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Cholesta-5,7-diene-3β,25-diol 67
．． Dissolve 4 mg in 200 ml of diethyl ether,
The resulting solution was heated to -2 to -5°C while passing argon gas through it.
Krypton fluoride excimer laser (
When the reaction mixture was irradiated with ultraviolet laser light with a wavelength of 248 nm for 18.75 minutes using an irradiation power of 1.5 W and a repetition rate of 70 Hz, the reaction mixture was analyzed by high performance liquid chromatography.
- conversion rate of diol is 91%, (6E)-9゜O-secocoresta-5(10), 6.8-1-Quen-3β,
The selectivity for 25-diol was 62%. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain (6E)-9,10-secocholester-5(10), 6.8-)-Quen-3β,25
-Diol31. Omg was obtained (yield 46%). This was dissolved in 120 ml of diethyl ether, 18.0 mg of 9-fluorenone was added to the resulting solution, and the mixture was heated using a fluorinated xenon excimer laser (irradiation power: 0.5°C) at a temperature within the range of -2 to -5°C while passing argon gas. When the reaction mixture was irradiated with ultraviolet laser light with a wavelength of 351 nm for 7 minutes using a high-performance liquid chromatography (6E)-9,10-secocoresta-5(10), 6. 8-triene-3β.

The conversion of 25-diol is 90%, (6Z)9.10-
Seco Core Star-5 (10), 6. B triene-3β,2
The selectivity of 5-diol was 86%. After the reaction is complete,
The reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to give (6Z)-
20.3 mg of 9,10 secocoresta-5(10), 6,8-triene 3β, 25-diol was obtained (yield 65%).
).

Ultraviolet absorption spectrum (λmax): 260 nm Mass spectrum (m/z): 400 (M''') Example 2 Cholesta-5,7-diene-3β,25-diol 67
．． Dissolve 4 mg in 200 ml of diethyl ether,
The resulting solution was heated to -2 to -5°C while passing argon gas through it.
Krypton fluoride excimer laser (
After the completion of the reaction, which was irradiated with ultraviolet laser light with a wavelength of 248 nm for 18.75 minutes using an irradiation power of 1.5 W and a repetition rate of 70 Hz, 9-fluorenone 30 was added to the reaction mixture.
．． Add 4 mg and bring to -2 to -5 while passing argon gas.
Xenon fluoride excimer laser (
A reaction mixture that was irradiated with ultraviolet laser light with a wavelength of 351 nm for 9 minutes using an irradiation power of 0.5 W and a repetition rate of 70 Hz was analyzed by high-performance liquid chromatography, and it was found that cholesta-5.7-diene-3β, 25- Diol conversion rate is 91%, (6Z)-9,10-secocholester-5(10), 6. 8-triene-3β, 25-
The selectivity of the diol was 74%. 1 After the reaction was completed, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography, showing the same physical properties as those obtained in Example 1 (6Z) -9,10-Secokore Star-5 (10
), 6.8-triene-3β,25-diol in 34.
5 mg was obtained (yield 51%).

Comparative Example 1 Cholesta-5,7-diene-3β,25-diol 67
．． Dissolve 4 mg in 200 ml of diethyl ether,
The obtained solution was irradiated with ultraviolet rays for 3 minutes at a temperature in the range of 5 to 10°C while passing argon gas through a Vycor filter using a 400W high-pressure mercury lamp. Analysis of the reaction mixture by high performance liquid chromatography revealed that cholesta-5,7-diene-3
The conversion rate of β,25-diol was 39%, (6Z)-9,
10-Secocholesta-5(1o), 6,8-triene-
The selectivity for 3β,25-diol was 44%. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain the same physical properties as those obtained in Example 1. 7.1 mg of (6Z)-9,10 Niseko cholesta-5(lO), 6,8-triene-3β,25-diol shown was obtained (yield 11%). Reference Example 1 The reaction was carried out in the same manner as in Example 2. By doing (6Z)-
A reaction mixture containing 9,10-secochoresta-5(10)6.8-1 liene-3β,25-diol was obtained 9. The reaction mixture was concentrated under reduced pressure, and 100 m of hexane was added to the residue.
1 was added thereto, and the mixture was heated under reflux for 2 hours under an argon atmosphere. After the reaction mixture was allowed to cool to room temperature, it was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain 9,10-secocoresta-5,7°10 (19
)-1-Quen-3β,25-diol 40.6 mg
(Yield: 60%) The physical properties of this product were consistent with the literature values.

Ultraviolet absorption spectrum (λmax) ・265n
m Mass spectrum (m/z): 400 (M”
) Comparative Example 2 By carrying out the reaction in the same manner as in Comparative Example 1, (6Z)-
A reaction mixture containing 9,10-secocoresta-5(10), 6,8-triene-3β, 25-diol was obtained.The reaction mixture was concentrated under reduced pressure, and 100ml of hexane was added to the residue.
was added and heated under reflux for 2 hours under an argon atmosphere.The reaction mixture was analyzed by high performance liquid chromatography, and the conversion rate of cholesta-5,7-diene-3β,25-diol was 43%, 9.10-secocholesta-
5. 7. 10 (19) -1
Lien − 3 β.

The selectivity for 25-diol was 42%.1 The reaction mixture was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain the same physical property values as those obtained in Reference Example 1. 9.10-Seco Core Star-5
,7,10(19)-triene-3β,25-diol (9.7 mg) was obtained (yield: 14%).

Example 3 Cholesta-5,7-thien-3β, 24.25 trio-
Dissolve 0.1 mg of Lua in 200 ml of diethyl ether ethanol mixed solution (volume ratio 2:1), and apply krypton fluoride excimer laser (irradiation power 1.5 W) to the resulting solution at a temperature within the range of -5 to 0°C. , repetition rate 70Hz)
UV laser light with a wavelength of 248 nm was
Analysis of the reaction mixture irradiated for 1 minute by high performance liquid chromatography revealed that cholesta-5,7 diene-3β
, 24.25-1-diol conversion rate is 91%, (8E
)-9,10-Secoco Lester-5(10), 6
．． 8-triene-3β
, 2 4.

The selectivity for 25-triol was 61%. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain (6E)-9,l O-ce)Drester 5( 10) 6.8-triene-3β, 24
．． Obtained 36.5 mg of 25-triol (yield 52%)
, this was mixed into a diethyl ether-ethanol mixed solution of 120
m 1 (volume ratio 2:1) and the resulting solution contains 9
- 19.8 mg of fluorenone was added, and fluorinated xenon excimer laser (irradiation power 0.5 W, number of repetitions 7
0 Hz) to emit ultraviolet laser light with a wavelength of 351 nm.
After completion of the 6 reactions, which were irradiated for 0 minutes, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography.
(6Z)-9,10-Secocoresta-5(10) exhibiting the following physical property values, 6. 8-
Triene-3β, 24
.

21.7 mg of 25-triol was obtained (yield 59%).

Ultraviolet absorption spectrum (λmax): 261 nm Mass spectrum (m/z): 416 (M'') Example 4 Cholesta-5,7-diene-3β, 24.'25-triol 0.1 mg was added to diethyl ether-ethanol. Dissolve in 200ml of mixed solution (volume ratio 2:1), and heat krypton fluoride excimer laser (irradiation power 1.5W, repetition rate 70Hz) at a temperature within the range of -5 to 0°C while passing argon gas through the resulting solution. ) using a wavelength of 248n
After the completion of the reaction, which was irradiated with ultraviolet laser light of m for 20.5 minutes, 30.4 mg of 9-fluorenone was added to the reaction mixture, and fluorinated xenon excimer laser was heated at a temperature within the range of -5 to 0°C while passing argon gas. (Irradiation power 0.5
When the reaction mixture was irradiated with ultraviolet laser light with a wavelength of 351 nm for 85 minutes using a high-speed liquid chromatography (W, repetition rate 70 Hz), cholesta-
Conversion of 5,7 diene-3β,24.25-triol was 90%, (6Z)-9,1o-secocoresta 5
(10), 8. 8-1-
Lien-3β, 24.

The selectivity for 25-triol was 67%. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography, showing the same physical properties as those obtained in Example 3 ( 6Z) 9.10-Secokore Star-5
(10), 8.8 triene-3β
, 24. 25-1- Rio-
36.0 mg of 36.0 mg (yield 51%) was obtained.

Reference Example 2 By carrying out the reaction in the same manner as in Example 4, (6Z)-
A reaction mixture containing 9,10-secocoresta-5(10)6, 8-triene-3β, and 24.25-triol was obtained. The reaction mixture was concentrated under reduced pressure, 100 ml of hexane was added to the resulting residue, and the mixture was evaporated for 2 hours under an argon atmosphere.
The mixture was heated to reflux for an hour. The reaction mixture was analyzed by high performance liquid chromatography, and the conversion of cholesta-5,7-diene-3β,24.25-hliol was 91%, 9
．． 10-Secokoresta-5,7,10(19)-
Triene-3β, 24.
25- triol selection rate is 68%
Met. After the reaction mixture was allowed to cool to room temperature, it was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain 9,10-secocoresta-5,7, which exhibits the following physical properties.
,10(19)-triene-3
β, 24.25- triol to 4
1.9 mg was obtained (yield 60%). The physical properties of this product were consistent with literature values.

Ultraviolet absorption spectrum (λmax): 265 nm Mass spectrum (m/z): 416 (M”) Example 5 In Example 2, cholesta-5,7-diene 3β, 25
- 25.26-0-isopropylidene-3-methoxycarbonyloxycholester-5,7-diene 25.26-diol 82.2 mg instead of 67.4 mg
was used, 29.1 mg of benzophenone was used instead of 30.4 mg of 9-fluorenone, and a xenon fluoride excimer laser (irradiation power 0.5 W, number of repetitions 70 H) was used.
Instead of irradiating ultraviolet laser light with a wavelength of 351 nm for 9 minutes using a nitrogen laser (irradiation power 0.1W1)
The reaction and separation operations were carried out in the same manner except that ultraviolet laser light with a wavelength of 337 nm was irradiated for 30 minutes using a repeating frequency of 20 Hz), and the following physical property values were obtained (6Z
)-25,26-〇-isopropylidene-3-methoxycarbonyloxy-9,10-secocoresta 5
(10), 6. 8- Tori
38.4 mg of ene-25,26 diol was obtained (yield 47%).

Ultraviolet absorption spectrum (λmax): 261 nm Mass spectrum (m/z): 514 (M”) Reference Example 3 By carrying out the reaction in the same manner as in Example 5, (6Z)-
25,26-0-isopropylidene-3-methoxycarbonyloxy-9,10-secocoresta-5(10),
A reaction mixture containing 6,8-triene and 25,26-diol was obtained.

After concentrating the reaction mixture under reduced pressure, 1 hexane was added to the residue.
The reaction mixture was heated under reflux for 2 hours under an argon atmosphere, allowed to cool to room temperature, and then concentrated under reduced pressure. 5 ml of methanol and 10 mg of p-h luenesulfonic acid were added to the residue, and the mixture was stirred at room temperature under an argon atmosphere for 4 hours.

The reaction mixture was neutralized with sodium bicarbonate, and methanol was distilled off under reduced pressure. The residue was diluted with ethyl acetate, washed successively with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. Add 5 ml of methanol and 20 ml of potassium hydroxide to the residue.
mg was added thereto, and the mixture was heated under reflux for 1 hour under an argon atmosphere.

After the reaction mixture was allowed to cool to room temperature, water was added, and the 6 extracts extracted with ethyl acetate were washed with brine, dried over sodium sulfate, and then concentrated under reduced pressure. The residue was purified by high performance liquid chromatography to obtain 9,10-secocoresta-5,7゜10 (1
9) -triene-3β,
25. 26 - Triol 41.3
mg (yield: 62%) The physical properties of this product were consistent with the literature values.

Ultraviolet absorption spectrum (λmax): 265 nm Mass spectrum (m/z): 416 (M”) Example 6 In Example 1, cholesta-5,7-diene 3β, 25
3β-(tetrahydrobilan-2-yl)oxycholester-5,7-cyen-24-one-25-ol instead of 67.4 mg of -diol 80. By performing the reaction and separation operation in the same manner except that Omg was used, (6Z)-3-β-(tetrahydrobilan-2-yl)oxy-9,10-secocholesta-5(1
0), 6.8-1 Lien-24-one-25-ol42
．． 7 mg (yield 53%) Ultraviolet absorption spectrum (1
m a x ) ・261 nm mass spectrum (m
/z): 500 (M'') Reference Example 4 By carrying out the reaction in the same manner as in Example 6, (6Z)-
3-β-(tetrahydrobilan-2yl)oxy-9,
10-Secocholesta-5(10),6.8-triene-
A reaction mixture containing 24-one-25ol was obtained. The reaction mixture was concentrated under reduced pressure, and 100 m of hexane was added to the residue.
1 was added thereto, and the mixture was heated under reflux for 2 hours under an argon atmosphere. After the reaction mixture was allowed to cool to room temperature, it was concentrated under reduced pressure.

The residue was dissolved in 5 ml of methanol, and 5 mg of pyridinium p-1-ruenesulfonate was added to the resulting solution.
Stirred at room temperature under argon atmosphere for 3 hours. The reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by high performance liquid chromatography to obtain 39.2 mg of 9゜10-secochoresta-5,7,10(19)trien-24-one-3β-25-diol exhibiting the following physical properties.
(yield 59%), and the physical properties of this product were consistent with the literature values.

Ultraviolet absorption spectrum (1m a x ) ・265n
m Mass spectrum (m/z): 414 (M”
) Example 7 70.7 mg of 3β-acetoxycholest-5,7-dien-25-ol was dissolved in 200 ml of diethyl ether, and the resulting solution was heated to
The fourth harmonic of YAG laser (irradiation power IW, repetition rate 50Hz H wave!% 266n) at a temperature within the range of 0°C
m) for 25.3 minutes, 30.4 mg of 9-fluorenone was added to the reaction mixture, and the third harmonic of the YAG laser (irradiation Power IW, repetition rate 50Hz;
A wavelength of 355 nm) was irradiated for 34 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography to obtain (6,2)-3β-acetoxy-9,1° Secocoresta-5(to), 6.8 Obtained 35.1 mg of -trien-25-ol (yield 50%)
.

Ultraviolet absorption spectrum (λmaχ): 262 nm Mass spectrum (m/z): , 442 (M") Reference Example 5 By carrying out the reaction in the same manner as in Example 7, (6Z)-
3β-acetoxy-9,10-secocholester-5 (10
) 6.8-1 Reaction mixture containing 25-ol was obtained.The reaction mixture was concentrated under reduced pressure, 100 ml of hexane was added to the residue, and the reaction mixture was heated under reflux for 2 hours under an argon atmosphere and cooled to room temperature. After being left to cool, it was concentrated under reduced pressure. 10 ml of methanol and 10 mg of potassium carbonate were added to the residue, and the mixture was stirred at room temperature under an argon atmosphere for 3 hours.
Stir for hours. The reaction mixture was diluted with water and extracted with ethyl acetate, the extracts were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by high performance liquid chromatography to obtain 9,10 Secocoresta-5,7,10 (19
)-triene 3β,25-diol (37.7 mg) (yield 59%).

Example 8 In Example 1, cholesta-5,7-diene 3β,25
-3β-tert- instead of 137.4 mg of diol
By performing the reaction and separation operation in the same manner except that 84.8 mg of butyldimethylsilyloxycholester-5,7-diene-24,25-diol was used, (6Z)-3β- exhibiting the following physical property values was obtained. tert-butyldimethylsilyloxy-910-secocoresta-5(10),6
．． 40.9 mg of 8-triene-24,25-diol
Obtained (yield 48%) Ultraviolet absorption spectrum (1 m a x ) ・261
n rn mass spectrum (m/z): 530 (M”
) Reference Example 6 By carrying out the reaction in the same manner as in Example 8, (6Z)-
3β-tert-butyldimethylsilyloxy-9,1
A reaction mixture containing 0-secocoresta-5(10) and 6.8-1-lien-24.25-diol was obtained. The reaction mixture was concentrated under reduced pressure, and the resulting residue was diluted with 100% hexane.
ml was added thereto, and the reaction mixture was heated under reflux for 2 hours under an argon atmosphere, allowed to cool to room temperature, and then concentrated under reduced pressure. The residue was dissolved in 10 ml of tetrahydrofuran, and 0.5 ml of 1N tetrabutylammonium fluoride-tetrahydrofuran solution was added to the resulting solution, followed by stirring at room temperature under an argon atmosphere for 4 hours. Water was added to the reaction mixture, extracted with ethyl acetate, and the extract was washed successively with aqueous sodium bicarbonate and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by high performance liquid chromatography to give 9, which shows the same physical properties as those obtained in Reference Example 3.
．． 10-Seco Coresta 5,7.10 (19)-to
Lien-3β, 24. 2
41.3 mg of 50 triol was obtained (yield 62%).

The separation operation of the compound (rV) from the metal object becomes extremely easy.

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 and R^2 each represent a hydrogen atom or a hydroxyl group protecting group, and X^1 is a hydrogen atom or Formula-OR
represents a group represented by ^3, and X^2 represents a hydrogen atom, or X^1 and X^2 together represent an oxo group, and Y represents a hydrogen atom or a group represented by the formula -OR^4 represents a group that is
(R^3 and R^4 each represent a hydrogen atom or a protecting group for a hydroxyl group) A 25-hydroxytaxerol derivative represented by the following is irradiated with ultraviolet laser light having a wavelength selected from a wavelength range of 280 to 400 nm. 25-hydroxy represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1, R^2, X^1, X^2 and Y are each as defined above) A method for producing a previtamin D derivative. 2. General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, X^1, X^2 and Y are each as defined in claim 1) Ultraviolet laser light having a wavelength selected from the wavelength range of 190 to 310 nm and ultraviolet laser light having a wavelength selected from the wavelength range of 280 to 400 nm and longer than the above-mentioned ultraviolet laser light. There are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. that are characterized by successive or simultaneous irradiation ▼ (wherein R^1, R^2, X^1, X^2 and Y are each defined above) ) A method for producing a 25-hydroxy previtamin D derivative. 3. General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, X^1, X^2 and Y are each as defined in claim 1) By irradiating the 25-hydroxyprovitamin D derivative with ultraviolet laser light having a wavelength selected from the wavelength range of 190 to 310 nm, the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R A 25-hydroxytaxerol derivative represented by
A general formula characterized by irradiation with an ultraviolet laser beam selected from the range of 0 to 400 nm and having a longer wavelength than the above-mentioned ultraviolet laser beam▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^ 1, R^2, X^1, X^2 and Y are each as defined above) A method for producing a 25-hydroxy previtamin D derivative.