JPH0725883A - 3,5-dihydroxy-1-octen-7-yne compound and its production - Google Patents

Abstract

PURPOSE:To a 3,5-dihydroxy-1-octen-7-yne compound useful as a synthetic intermediate for activated vitamin D3 on an industrial scale at a low cost by using a step to react a specific ol compound with silyl acetylide. CONSTITUTION:This yne compound of the formula I [R<1> and R<2> are H, tri(l-7C hydrocarbon)silyl, acyl of the formula C(=O)R<4> (R<4> is H or 1-6C hydrocarbon group) or group forming acetal bond together with 0 atom of OH group; R<3> is tri(1-7C hydrocarbon)acyl] is produced via a 3,5-dihydroxy-1-octen-7-yne compound of the formula III obtained by reacting a 5,6-epoxy-1-hexen-3-ol compound of the formula II [R<5> is H, tri(1-7C hydrocarbon)silyl or group forming acetal bond together with 0 atom of OH group; the absolute configuration of 5-site is S and that of 3-site is R or S] with a metal tri(1-7C hydrocarbon)silyl acetylide.

Description

Detailed Description of the Invention

[0001]

The present invention relates to 3,5-dihydroxy-which can be used as a synthetic intermediate for active vitamin D ₃ 's.
The present invention relates to 1-octen-7-ynes and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, a novel synthesizing active vitamin D ₃ has been obtained by reacting an ene-yne compound represented by the following formula (VI) with a bicyclic compound represented by the following formula (VII). Method announced (Trost, BM; J. Am. Chem. So
c. 1992, 114, 1924, Trost, BM; ibid.,
1992, 114, 9386).

[0003]

[Chemical 6]

Among them, regarding the production method of the ene-yne compound represented by the above formula (VI) which is an intermediate for the synthesis of active vitamin D ₃ , the synthesis method shown in the following reaction process chart has been proposed. . The term "dl" here refers to a racemic mixture of a compound having the absolute configuration shown therein and its enantiomer.

[0005]

[Chemical 7]

[0006]

In the above conventional method, the racemic mixture is optically resolved to obtain the desired optically active compound, and half of the product is wasted. .

[0007]

DISCLOSURE OF THE INVENTION The inventors of the present invention have focused on the above-mentioned problems and have found that the optically active 3,5-dihydroxy-1-
As a result of earnest research on a method for producing octene-7-ynes, the present invention has been accomplished. That is, the present invention provides the following formula (I)

[0008]

[Chemical 8]

[Wherein R ¹ and R ² are the same or different,
Hydrogen atom, tri (C ₁ -C ₇ hydrocarbon) silyl group, -C
(= O) acyl group represented by R ⁴ (provided that R ⁴ represents. A hydrogen atom or a C ₁ -C ₆ hydrocarbon group) represent a group forming a, or an acetal bond together with the hydroxyl group oxygen atom, R ³ Represents a tri (C ₁ -C ₇ hydrocarbon) silyl group. ] 3,5-dihydroxy-1-octene-7-ynes represented by

In the present invention, in the compound represented by the formula (I), the absolute configuration at the 3-position is the S configuration and the absolute configuration at the 5-position is the R configuration. , 5-dihydroxy-1-octen-7-ynes, and 3,5-dihydroxy represented by the following formula (III) in which the absolute configuration at the 3-position is the R configuration and the absolute configuration at the 5-position is the R configuration ―1―
Includes Octene-7-ynes.

[0011]

[Chemical 9]

[Wherein R ¹ , R ² and R ³ are the same as defined in the above formula (I). ]

[0013]

[Chemical 10]

[In the formula, R ¹ , R ² and R ³ are the same as defined in the above formula (I). In the present invention, the above formula (I
3,5-dihydroxy-represented by I) or (III)
A method for producing 1-octene-7-ynes is also included. That is, the following formula (IV)

[0015]

[Chemical 11]

[Wherein R ⁵ is a hydrogen atom and tri (C ₁ -C ₇
(Hydrocarbon) represents a group that forms an acetal bond together with an oxygen atom of a silyl group or a hydroxyl group. The absolute placement of 5th place is S
A configuration, and the absolute configuration at the third position is the R configuration or the S configuration. ] 5,6-Epoxy-1-hexene-3 represented by
-Reacting a metal tri (C ₁ -C ₇ hydrocarbon) silyl acetylide with an all compound to give the following formula (V)

[0017]

[Chemical 12]

[In the formula, R ³ is the same as defined in the above formula (I). R ⁵ has the same definition as in the above formula (IV). ] 3,5-Dihydroxy-1-octene-7-yne represented by the formula [3], 3,5-dihydroxy-1 represented by the above formula (II) or (III) -A method for producing octene-7-ynes.

Here, the hydroxyl group at the 5-position of the compound represented by the above formula (V) can be converted to R ¹ O in the above formula (II) or (III) by the method shown in Reference Example 5, for example. . In the compound represented by the formula (II) or (III), R ² is an acyl group represented by —C (═O) R ⁴ (provided that R ⁴ is a hydrogen atom or a C _{1 to} C ₆ hydrocarbon). The compound represented by the formula (1) is obtained by substituting the substituent R ⁵ with a corresponding acyl group after obtaining the compound represented by the above formula (V).

Further, the enantiomer of the compound represented by the above formula (II) or (III) is obtained by using the enantiomer instead of the compound represented by the above formula (IV) as a starting material and performing the same reaction. Barrel 3,5-dihydroxy-1-octene-7-
Inns can be produced. These production methods can be summarized as a production method of 3,5-dihydroxy-1-octen-7-ynes represented by the above formula (I).

In the above formulas (I) to (III), R ¹ and R
² are the same or different and each represents a hydrogen atom or tri (C ₁ -C ₇
(Hydrocarbon) silyl group, an acyl group represented by —C (═O) R ⁴ (provided that R ⁴ represents a hydrogen atom or a C _{1 to} C ₆ hydrocarbon group), or an acetal bond together with an oxygen atom of a hydroxyl group. Represents a group to be formed. For example, as the trihydrocarbon silyl group, tri (C ₁
~ C ₄ alkyl) silyl group, di (C ₁ -C ₄ alkyl) phenylsilyl group such as dimethylphenylsilyl group,
Diphenyl such as t-butyldiphenylsilyl group (C
₁ -C ₄ alkyl) silyl group, may be mentioned as being preferred triphenylsilyl group. Above all, t
-Butyldiphenylsilyl group and t-butyldimethylsilyl group are particularly preferable. Further, R ¹ and R ² may be bonded to each other to form a ring.

Also, R¹Or R²But -C (= O) R
^Four(However, R^FourIs a hydrogen atom or C ₁~ C₆Hydrocarbon group
Represents), for example, acetyl group, pro
Such as pionyl group and butyryl group (C₁~ C_Four) Aliphatic
Examples include acyl groups and benzoyl groups derived from saturated monocarboxylic acids.
You can Of these, an acetyl group is preferable.

When R ¹ or R ² is a group which forms an acetal bond with an oxygen atom of a hydroxyl group, for example, a methoxymethyl group, a 1-ethoxyethyl group,
Examples thereof include 2-methoxy-2-propyl group, (2-methoxyethoxy) methyl group, 2-tetrahydropyranyl group, and benzyloxymethyl group. Of these, a 2-tetrahydropyranyl group is preferable.

Further, R ⁵ in the above formula (IV) or (V) is equal to R ² in the above formulas (I) to (III) except that it is not an acyl group.

In the above formulas (I) to (III) and (V), R ³ represents a tri (C ₁ -C ₇ hydrocarbon) silyl group. Preferred examples of the tri (C ₁ -C ₇ hydrocarbon) silyl group include tri (C ₁ -trimethylsilyl group, triethylsilyl group, and t-butyldimethylsilyl group.
₁ -C ₄ alkyl) silyl group, di (C ₁ -C ₄ alkyl) phenyl silyl groups such as dimethylphenylsilyl group, t- butyl diphenyl (C ₁ -C ₄ alkyl) silyl groups such as diphenyl silyl group, Examples thereof include a triphenylsilyl group. Among these, birds (C
₁ -C ₄ alkyl) silyl group are preferred, trimethylsilyl group, triethylsilyl group is particularly preferred.

Further, the compound represented by the above formula (I) can be easily led to the above formula (VI) according to the following process chart as shown in Examples.

[0027]

[Chemical 13]

Also in the compound represented by the above formula (II) or (III), the substituent R ³ can be similarly derivatized to a hydrogen atom.

On the other hand, the 5,6-epoxy-1-hexen-3-ols represented by the above formula (IV) can be produced according to the following process chart as shown in Examples.

[0030]

[Chemical 14]

Further, the 5-hexene-1,2,4-triol represented by the formula (VIII), which is the starting material in the above process diagram, is manufactured by the method described in JP-A-2-286647. , And tetrahedron (Tetrahedron
), 1979, 35 , 933 to 940 and the like. The outline of an example thereof is shown in the following process chart.

[0032]

[Chemical 15]

That is, a natural inexpensive optically active compound called malic acid can be used as a starting material. As a result, without the difficult process of optical division,
It has become possible to produce active vitamin D ₃ . However, the starting material of the present invention is not limited to the production method described here.

As the reaction solvent in the method for producing 3,5-dihydroxy-1-octen-7-ynes of the present invention, THF, diethyl ether, hexane and the like can be mentioned. Any solvent may be used as long as it does not affect. The reaction temperature and the reaction time are not particularly limited, but are usually -20 to 50 ° C and 1
The reaction is complete between 0 minutes and 1 day.

Further, the 3,5-dihydroxy-1 of the present invention
- metal used in the manufacturing method of octenes 7- ynes birds birds (C ₁ -C ₇ hydrocarbon) Shiriruasechirido (C ₁
To C ₇ hydrocarbon) silyl group, tri (C ₁ -C ₄ alkyl) silyl group such as trimethylsilyl group, triethylsilyl group, t-butyldimethylsilyl group, di (C ₁ hydrocarbon group) such as dimethylphenylsilyl group. ~ C ₄ alkyl)
A phenylsilyl group, a diphenyl (C ₁ -C ₄ alkyl) silyl group such as t-butyldiphenylsilyl group, a triphenylsilyl group and the like are used, and a tri (C ₁ -C ₄ alkyl) silyl group is particularly preferable. Can be mentioned.

The metal portion of the metal tri (C ₁ -C ₇ hydrocarbon) silylacetylide includes lithium, magnesium halide, sodium, dimethylaluminum,
Diethyl aluminum and the like, and particularly preferably,
Examples include lithium, diethylaluminum, and dimethylaluminum.

Among the metal tri (C ₁ -C ₇ hydrocarbon) silyl acetylides, for the tri (C ₁ -C ₇ hydrocarbon) silyl acetylenyl magnesium halides, the corresponding trihydrocarbon silyl acetylene and Grignard reagent are used. It can be obtained by reacting. Lithium tri (C ₁ -C ₇ hydrocarbon) silylacetylide is the corresponding trihydrocarbon silylacetylene and n-butyllithium,
It can be obtained by reacting hydrocarbon lithium such as t-butyllithium, methyllithium and phenyllithium.

Diethylaluminum tri (C ₁ -C ₇ hydrocarbon) silylacetylide or dimethylaluminum tri (C ₁ -C ₇ hydrocarbon) silylacetylide is the lithium tri (C ₁ -C ₇ hydrocarbon) obtained by the above method. hydrogen)
It can be obtained by reacting silyl acetylide with diethylaluminum chloride or dimethylaluminum chloride.

The production method of the present invention is not limited to simple metal acetylides such as lithium acetylide, but tri (C
It is characterized by using a ( _{1 to} C ₇ hydrocarbon) silyl compound, and finally, a practical yield was obtained.

Specific preferred examples of the 3,5-dihydroxy-1-octen-7-ynes of the present invention include the following compounds. (3S, 5R) -3,5-Dihydroxy-8-trimethylsilyl-1-octen-7-yne (3S, 5R) -3-Hydroxy-5- (t-butyldiphenylsilyloxy) -8-trimethylsilyl-1-
Octene-7-yne (3S, 5R) -3- (t-butyldimethylsilyloxy) -5- (t-butyldiphenylsilyloxy) -8
-Trimethylsilyl-1-octene-7-yne (3S, 5R) -3,5-di (t-butyldimethylsilyloxy) -8-trimethylsilyl-1-octene-7
-In (3S, 5R) -3,5-di (t-butyldiphenylsilyloxy) -8-trimethylsilyl-1-octene-
7-yne (3S, 5R) -3-hydroxy-5- (2-tetrahydropyranoxy) -8-trimethylsilyl-1-octene-7-yne (3S, 5R) -3-hydroxy-5-methoxymethyloxy -8-Trimethylsilyl-1-octene-7-yne (3S, 5R) -3,5-di (2-tetrahydropyranoxy) -8-trimethylsilyl-1-octene-7-yne (3S, 5R) -3 , 5-dimethoxymethyloxy-8
-Trimethylsilyl-1-octene-7-yne (3S, 5R) -3-hydroxy-5-acetoxy-8
-Trimethylsilyl-1-octene-7-yne (3S, 5R) -3,5-diacetoxy-8-trimethylsilyl-1-octene-7-yne (3R, 5R) -3,5-dihydroxy-8-trimethylsilyl-1 -Octene-7-yne (3R, 5R) -3-hydroxy-5- (t-butyldiphenylsilyloxy) -8-trimethylsilyl-1-
Octene-7-yne (3R, 5R) -3- (t-butyldimethylsilyloxy) -5- (t-butyldiphenylsilyloxy) -8
-Trimethylsilyl-1-octene-7-yne (3R, 5R) -3,5-di (t-butyldimethylsilyloxy) -8-trimethylsilyl-1-octene-7
-In (3R, 5R) -3,5-di (t-butyldiphenylsilyloxy) -8-trimethylsilyl-1-octene-
7-yne (3R, 5R) -3-hydroxy-5- (2-tetrahydropyranoxy) -8-trimethylsilyl-1-octene-7-yne (3R, 5R) -3-hydroxy-5-methoxymethyloxy -8-Trimethylsilyl-1-octene-7-yne (3R, 5R) -3,5-di (2-tetrahydropyranoxy) -8-trimethylsilyl-1-octene-7-yne (3R, 5R) -3 , 5-dimethoxymethyloxy-8
-Trimethylsilyl-1-octene-7-yne (3R, 5R) -3-hydroxy-5-acetoxy-8
-Trimethylsilyl-1-octen-7-yne (3R, 5R) -3,5-diacetoxy-8-trimethylsilyl-1-octene-7-yne

[0041]

EXAMPLES Examples of the present invention will be shown below together with reference examples, but the present invention is not limited to these examples.

[0042]

Reference Example 1 Synthesis of 3- (t-butyldiphenylsilyloxy) -5,6-epoxy-1-hexene ( 2 )

[0043]

[Chemical 16]

4- (t-butyldiphenylsilyloxy) -5-hexene-1,2-diol ( 3 ) 2.9 g
Was dissolved in 8 ml of pyridine, and the mixture was stirred under ice cooling. P here
-Toluenesulfonic acid chloride (1.8 g) was added, the temperature was returned to room temperature, and the mixture was stirred overnight.

20 ml of diethyl ether was added to the reaction solution, the precipitate was filtered off, the precipitate was thoroughly washed with diethyl ether, and the organic layer was collected and washed with saturated aqueous copper sulfate solution. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to obtain a crude product ( 4 ).

This was dissolved in 20 ml of methylene chloride, to which a solution of 0.6 g of sodium hydroxide in 2 ml of water and 20 ml of methanol was added and reacted.

After stirring overnight at room temperature, the mixture was neutralized with saturated aqueous ammonium chloride and extracted with methylene chloride. The organic layers were collected, dried over anhydrous magnesium sulfate, and after concentration, the residue was purified by silica gel column (hexane / ethyl acetate = 5/1) to obtain 2.33 g of the desired product ( 2 ). (Yield 81%) ¹ H-NMR (CDCl ₃ δppm) 1.00 (s, 9H), 1.5 to 1.8 (m, 2H),
2.2-2.3 (m, 1H), 2.5-2.7 (m, 1)
H), 2.8 to 3.0 (m, 1H), 4.31 (m, 1)
H), 4.85 to 5.15 (m, 2H), 5.7 to 6.
0 (m, 1H), 7.2 to 7.5 (m, 6H), 7.5
~ 7.8 (m, 4H)

[0048]

Example 1 Synthesis of 3- (t-butyldiphenylsilyloxy) -5-hydroxy-8-trimethylsilyl-1-octen-7-yne ( 1 )

[0049]

[Chemical 17]

212 μl of trimethylsilylacetylene was dissolved in 1.5 ml of hexane, and the mixture was stirred under ice cooling in a nitrogen atmosphere. 0.9 ml of a hexane solution of n-butyllithium (1.68 mol / liter) was put therein. Furthermore, a solution of diethylaluminum chloride in hexane (1
(ml / liter) 1.5 ml was added and stirred. Here, 3- (t-butyldiphenylsilyloxy) -5,
6-Epoxy-1-hexene ( 2 ) in hexane (1
76 mg / 0.8 ml) was added. After stirring for 2 hours under ice-cooling, 5 ml of methylene chloride, 0.5 ml of water, and 0.63 g of sodium fluoride were put into the reaction solution and vigorously stirred.

The insoluble material was filtered off, the precipitate was washed well with diethyl ether, the organic layer was concentrated, and the residue was purified by silica gel column (hexane / ethyl acetate = 8/1) to obtain 202 mg of the desired product ( 1 ). Got (Yield 90%) ¹ H-NMR (CDCl ₃ δppm) 0.05 (s, 9H), 0.93 to 0.95 (9H),
1.5-1.7 (m, 2H), 2.1-2.3 (m, 2)
H), 3.6-4.0 (m, 1H), 4.2-4.5.
(M, 1H), 4.7 to 5.0 (m, 2H), 5.55
Up to 5.85 (m, 1H), 7.2 to 7.5 (m, 6)
H), 7.5-7.7 (m, 4H)

[0052]

[Reference Example 2] 3- (t-butyldiphenylsilyloxy) -5-hydroxy-1-octene-7-yne ( 5 )
And the synthesis of ( 6 )

[0053]

[Chemical 18]

3- (t-Butyldiphenylsilyloxy) -5-hydroxy-8-trimethylsilyl-1-octen-7-yne ( 1 ) 192 mg was added to methanol 4.0.
It was dissolved in ml, 69 mg of potassium carbonate was added, and the mixture was stirred overnight at room temperature under a nitrogen atmosphere. Add diethyl ether,
The insoluble material was filtered off, the precipitate was washed well with diethyl ether, the organic layer was concentrated, and the residue was purified by silica gel column (hexane / ethyl acetate = 8/1) to give the desired product ( 5 ) as 3
9 mg (yield 24%) and 95 mg (yield 58%) of the desired product ( 6 ) were obtained.

Regarding the configurations of the compounds ( 5 ) and ( 6 ), they were introduced into the acetonide form ( 9 ) or ( 10 ), and the structure was determined from their ¹³ C-NMR measurement values. Compound ( 5 ) ¹ H-NMR (CDCl ₃ δppm) 1.07 (9H), 1.7 to 1.9 (m, 2H), 1.
97 (t, 2H, J = 2.6 Hz), 2.2 to 2.4
(M, 2H), 3.35 (d, 1H, J = 2.3H
z), 4.0 to 4.2 (m, 1H), 4.3 to 4.4.
(M, 1H), 5.02 (d, 1H, J = 11Hz),
5.05 (d, 1H, J = 17Hz), 5.83 (dd
d, 1H, J = 6, 11 & 17 Hz), 7.4 to 7.7.
(M, 10H) Compound ( 6 ) ¹ H-NMR (CDCl ₃ δppm) 1.06 (9H), 1.6 to 1.8 (m, 2H), 1.
98 (t, 2H, J = 2.6Hz), 2.2-2.3
(M, 2H), 2.47 (d, 1H, J = 4Hz),
3.8-4.0 (m, 1H), 4.3-4.4 (m, 1)
H), 4.8 to 5.0 (m, 2H), 5.78 (dd
d, 1H, J = 6, 10.2 & 16.8 Hz), 7.2
~ 7.8 (m, 10H)

[0056]

[Reference Example 3] 3,5-dihydroxy-1-octene-7
-Synthesis of in ( 7 ) and ( 8 )

[0057]

[Chemical 19]

3- (t-butyldiphenylsilyloxy) -5-hydroxy-1-octene-7-yne ( 5 )
Dissolve 757.2 mg in 8 ml of THF and stir under ice cooling, and add tetrabutylammonium fluoride T
Add 4 ml of HF solution (1 mol / liter), and add 1.5
Stir for hours. 10 ml of hexane was added to the reaction solution, and this solution was added to a silica gel column (hexane / ethyl acetate = 1 /
Purified by placing on 1). 280 mg of the target product ( 7 ) was obtained.

3- (t-butyldiphenylsilyloxy) -5-hydroxy-1-octene-7-yne ( 6 )
Was similarly treated to obtain a diol ( 8 ). Compound ( 7 ) ¹ H-NMR (CDCl ₃ δppm) 1.7 to 2.0 (m, 2H), 2.04 (dd, 1H,
J = 2.64 & 5.28 Hz, 2.39 (dd, 2)
H, J = 2.64 & 5.94 Hz, 2.9 (brs,
2H, J = 2.3 Hz), 4.05 to 4.25 (m, 1
H), 4.4 to 4.6 (m, 1H), 5.14 (dt,
1H, J = 1.32 & 10.6 Hz), 5.28 (d
t, 1H, J = 1.65 & 17.1 Hz), 5.91
(Ddd, 1H, J = 6, 10.56 & 17.1 Hz) Compound ( 8 ) ¹ H-NMR (CDCl ₃ δppm) 1.6 to 1.76 (m, 1H), 1.83 (dt, 1)
H, J = 2.97 & 14.25 Hz), 2.06 (d
d, 1H, J = 2.64 & 5.28Hz), 2.41
(Dd, 1H, J = 2.64 & 5.94Hz), 4.0
5 to 4.25 (m, 1H), 4.4 to 4.6 (m, 1)
H), 5.13 (dlike, 2H, J = 10.56H)
z), 5.27 (dlike, 1H, J = 17.16H
z), 5.89 (ddd, 1H, J = 5.94, 10.
56 & 17.16Hz)

[0060]

[Reference Example 4] 3,5-dihydroxy-1-octene-7
Synthesis of -in-3,5-acetonide ( 9 ) and ( 10 )

[0061]

[Chemical 20]

3,5-dihydroxy-1-octene-7
128 mg of -yne ( 7 ) was dissolved in 10 ml of 2,2-dimethoxypropane, 16 mg of camphorsulfonic acid was added, and the mixture was stirred at room temperature overnight. Diethyl ether 40 here
After adding ml, the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give the desired product ( 9 ) 15
1 mg was obtained.

3,5-dihydroxy-1-octene-7
-In ( 8 ) was also treated in the same manner, leading to the acetonide form ( 10 ). Compound ( 9 ) ¹ H-NMR (CDCl ₃ δppm) 1.38 (s, 6H), 1.8 to 2.0 (m, 2H),
1.99 (t, 1H, J = 2.64 Hz), 2.42
(Dddd, 2H, J = 2.64, 5.25, 16.5
0 & 30.35 Hz), 4.0 to 4.2 (m, 1H),
4.4-4.5 (m, 1H), 5.15 (dlike,
1H, J = 10.56 Hz), 5.23 (dlike,
1H, J = 17.16 Hz), 5.9 (ddd, 1H,
J = 5.94, 10.56 & 17.16 Hz) ¹³ C-NMR (CDCl ₃ δppm) 24.93, 25.54, 25.64, 36.28, 6
5.00, 67.87, 69.94, 80.32, 10
0.52,115.26,138.45 Compound ( 10 ) ¹ H-NMR (CDCl ₃ δppm) 1.30 (dd, 1H, J = 11.54 & 24.42H
z), 1.43 (s, 3H), 1.48 (s, 3H),
1.82 (dt, 1H, J = 2.64 & 12.86H
z), 2.01 (t, 1H, J = 2.64), 2.28.
(Ddd, 1H, J = 2.64, 7.92 & 16.49
Hz), 2.48 (ddd, 1H, J = 2.64, 4.
95 & 16.50 Hz), 3.9 to 4.1 (m, 1
H), 4.2 to 4.4 (m, 1H), 5.17 (dt,
1H, J = 1.32 & 10.56Hz, 5.28 (d
t, 1H, J = 1.32 & 17.16 Hz), 5.83
(Ddd, 1H, J = 5.94, 10.56 & 16.4
9 Hz) ¹³ C-NMR (CDCl ₃ δppm) 19.77, 26.17, 30.03, 35.83, 6
7.49, 70.06, 70.37, 80.13, 9
8.92, 115.56, 138.44

[0064]

[Reference Example 5] 3- (t-butyldiphenylsilyloxy) -5- (t-butyldimethylsilyloxy) -1-
Synthesis of Octene-7-yne ( 11 )

[0065]

[Chemical 21]

3- (t-butyldiphenylsilyloxy) -5-hydroxy-1-octene-7-yne ( 5 )
138 mg was dissolved in methylene chloride 5 ml, dimethylaminopyridine 134 mg was added, and the mixture was stirred under ice cooling, t-butyldimethylchlorosilane 83 mg was added, and the mixture was stirred overnight. 30 ml of hexane was added to the reaction solution, which was washed with saturated aqueous potassium hydrogen sulfate solution, saturated aqueous sodium hydrogen carbonate solution and saturated saline solution,
The residue obtained after drying over anhydrous magnesium sulfate and concentration was applied to a silica gel column (hexane / ethyl acetate = 19/1).
Purified in. 167 mg of the target product ( 11 ) was obtained. (Yield 94%) 3- (t-Butyldiphenylsilyloxy) -5-hydroxy-1-octene-7-yne ( 6 ) was treated in the same manner to obtain a disilyl compound ( 12 ). Compound ( 11 ) ¹ H-NMR (CDCl ₃ δppm) −0.04 (s, 3H), 0.01 (s, 3H), 0.
83 (s, 9H), 1.05 (s, 9H), 1.7-
2.2 (m, 3H), 2.2-2.3 (m, 2H),
3.7-3.9 (m, 1H), 4.2-4.4 (m, 1)
H), 4.8 to 5.0 (m, 2H), 5.7 to 5.9.
(M, 1H), 7.2-7.5 (m, 6H), 7.6-
7.8 (m, 4H) Compound ( 12 ) ¹ H-NMR (CDCl ₃ δppm) -0.09 (s, 3H), 0.00 (s, 3H), 0.
78 (s, 9H), 1.06 (s, 9H), 1.8-
2.0 (m, 3H), 2.2-2.3 (m, 2H),
3.7 to 3.9 (m, 1H), 4.2 to 4.35 (m,
1H), 4.8 to 5.0 (m, 2H), 5.7 to 5.9
(M, 1H), 7.3 to 7.5 (m, 6H), 7.6 to
7.8 (m, 4H)

[0067]

INDUSTRIAL APPLICABILITY The optically active 3,5-dihydroxy-1-octen-7-ynes of the present invention can be used as an intermediate for producing a vitamin D ₃ derivative. Further, according to the method for producing an optically active 3,5-dihydroxy-1-octen-7-yne of the present invention, the desired product can be obtained without optical resolution, which is industrially useful.
In particular, a raw material derived from malic acid can be used, which is advantageous in terms of cost.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kiyoshi Taka Takano 1 Furo-cho, Chikusa-ku, Nagoya-shi, Aichi Nagoya University International Residence A-402

Claims (6)

[Claims] 1. The following formula (I): [Wherein R ¹ and R ² are the same or different and each represents a hydrogen atom, a tri (C ₁ -C ₇ hydrocarbon) silyl group, —C (═O) R ⁴
An acyl group represented by (wherein R ⁴ is a hydrogen atom or C ₁
~C represents a ₆ hydrocarbon group. ), Or a group forming an acetal bond with the oxygen atom of the hydroxyl group, and R ³ represents a tri (C ₁ -C ₇ hydrocarbon) silyl group. ] 5,5-Dihydroxy-1-octene-7-ynes represented by 2. The 3,5-dihydroxy-1- according to claim 1, which is represented by the following formula (II), wherein the absolute configuration at the 3-position is the S configuration and the absolute configuration at the 5-position is the R configuration. Octene-7
-Inns. [Chemical 2] [Wherein R ¹ , R ² and R ³ are the same as defined in the above formula (I). ] 3. The 3,5-dihydroxy-1- according to claim 1, which is represented by the following formula (III), wherein the absolute configuration at the 3-position is the R configuration and the absolute configuration at the 5-position is the R configuration. Octene
7-ins. [Chemical 3] [Wherein R ¹ , R ² and R ³ are the same as defined in the above formula (I). ] 4. The following formula (IV): [In the formula, R ⁵ represents a hydrogen atom, a tri (C ₁ -C ₇ hydrocarbon) silyl group or a group forming an acetal bond with the oxygen atom of the hydroxyl group. The absolute arrangement of the 5th place is S arrangement, and 3
The absolute configuration of the positions is R configuration or S configuration. ] 5,6-epoxy-1-hexene-3-ol represented by
Metal tri (C ₁ -C ₇ hydrocarbon) silyl acetylide is reacted to give the following formula (V): [In formula, R < ³ > is the same as the definition of said formula (I). R ⁵ has the same definition as in the above formula (IV). ] 3,5-Dihydroxy-1-octene-7-yne represented by the formula [3], 3,5-dihydroxy-1 represented by the above formula (II) or (III) -Octene-7-yne production method. 5. The production method according to claim 4, wherein the metal part of the metal tri (C ₁ -C ₇ hydrocarbon) silylacetylide is lithium, diethylaluminum or dimethylaluminum. 6. The tri (C ₁ -C ₇ hydrocarbon) silyl group of the metal tri (C ₁ -C ₇ hydrocarbon) silyl acetylide is
The production method according to claim 4 or 5, which is a trimethylsilyl group, a triethylsilyl group or a t-butyldimethylsilyl group.