JPH0768208B2 - 22,23-seco-1,7,8-trihydroxyvitamin D or derivative thereof and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial field of application> The present invention relates to a novel 22,23-seco-1,7,8-trihydroxyvitamin D or a derivative thereof and the compound, 7,8-dihydroxyvitamin D. ₂ or a method for producing it from a derivative thereof.

<< Conventional Technology >> Vitamin D plays an important role in bone formation by regulating intestinal calcium absorption and bone mineral resorption, and its metabolic activity and 1,25-dihydroxyvitamin D ₃ Recently, a detailed study of the mechanism of action has been revealed (HFDe Luca, et al., “Ann, Rev. Biochem”, Vol. 52, P.
411, 1983); N. Ikekawa, "Medicinal Chem Reviws,"
Volume 7, P.333.1987).

Recently, 1,25-dihydroxyvitamin D ₃ has been reported to strongly suppress the proliferation of mouse myeloid leukemia cells (MI) in vitro and promote the differentiation into monocyte macrophages (E.Abe,
Others, "Proc.Natl.Acad.Sci.USA," Vol.78, P.2936,1
Since 981), induction of differentiation of various tumor cells has been reported (T. Suda, et al., Bone & Mineral Res./4.ed.WAPe.
ck, Elsevier, Amsterdam, Pl, 1986), new prospects for the vitamin D field are expected.

Attempts have been made to use it for the treatment of leukemia (KH Robert, et al., “Scand, I. Haematel, Su.
ppl, "Vol. 44, p. 36, 61, 1986), and rapid progress in this field is expected.

By the way, in order to exhibit the above-mentioned effects, most of the active compounds have a hydroxyl group at the 1α-position of the A ring portion thereof, and therefore the 1α-hydroxyl group is considered to be an essential substituent.

Therefore, until now, the synthesis of 1α-hydroxyvitamin D derivatives has been actively carried out (N. Ikekewa, et al.,
"Organic Synthetic Chemistry" Volume 37, P.755, 1979; C. Kaneko, "Organic Synthetic Chemistry" Volume 33, P.75, 1975; B, Lythgoe, "Chem.So.
c. Rev. ”, Volume 9, P.449, 1980; R. Pardo, Others,“ Bul
l. De La Soc. Chim. De Fr. ”P. 98, 1985).

As can be seen in the above review, most of the previous synthesis is
Starting from the synthesis of 1α-hydroxylated steroid and converting it to the corresponding 1α-hydroxy-5,7-dienesterol derivative, the desired vitamin D derivative is obtained by a well-known photochemical method. It is an inefficient method that requires.

Moreover, each derivative starts from the synthesis of the 1α-hydroxylated steroid each time, which requires a lot of trouble.

Here, in order to improve the above problems, a 22,23-seco-1α-hydroxyvitamin D derivative was set as a common synthetic intermediate for the synthesis of various 1α-hydroxyvitamin D derivatives, and the synthesis of the compound and its The following reports have been made on the conversion of compounds into various 1α-hydroxyvitamin D derivatives.

1) Vitamin D ₂ to 25-hydroxy and 1α, 25-
Synthesis of dihydroxyvitamin D ₃ , RHHesse, etc.,
"J. Org. Chem." Vol. 51, P. 4819, 1986 2) Vitamin D C-22 aldehyde, a key intermediate for the synthesis of modified side chain vitamin D derivatives, HFDe Luca, others, "Te
trahedron Lett, ”Vol. 28, P.6129, 1987 The above example 1) shows that the vitamin D form is once transvitamin D form, and the C (1) position is allyl-oxidized, and this is again converted to the vitamin form by photoreaction. To convert to 2)
In the reported example, a vitamin body is once converted to a 3,5-cyclovitamin D body, and then allyl oxidation is carried out at the C (1) position to convert it into a vitamin D body again 1) and 2). In all cases, the yield of allylic oxidation was not very good, and in the case of 1), a photoreaction was required to convert the trans form to the cis form, and in the case of 2), the cyclovitamin D form was converted. When converting to vitamin D form, there is a defect that a trans form is also produced as a by-product.

<< Problems to be Solved by the Invention >> The present inventor has conducted extensive studies to solve the drawbacks of the conventional synthesis method, and found that 7,23-dihydroxyvitamin D ₂ or its derivative has a double-position at the 22- and 23-positions. A novel 22,23-seco-1α (or 1β), 7,8 by selectively cleaving the bond
A method of producing trihydroxyvitamin D or a derivative thereof and further easily introducing a hydroxyl group directly into the 1-position of the novel compound by allyl oxidation, which is essentially different from the conventional method We have found an effective and efficient method. Accordingly, it is an object of the present invention to provide useful said novel compounds, to provide a process for preparing said novel compounds utilizing said selective cleavage, and to said novel compounds by said allyl oxidation. It is to provide a method for introducing a hydroxyl group.

<< Means for Solving the Problems >> Therefore, the present invention provides a compound represented by the general formula [X] [In the formula, R ₁ , R ₂ and R ₃ represent the same or different hydrogen atoms or a hydroxy protecting group, R ₄ represents an aldehyde group or —CH ₂ OR ₅ (R ₅ represents a hydrogen atom or a hydroxy protecting group), X represents a hydrogen atom, a hydroxy group or a derivative group thereof].

The present invention also provides a compound represented by the general formula [I] (In the formula, R ₁ , R ₂ and R ₃ represent the same or different hydrogen atom or hydroxy protecting group) 7,8-dihydroxyvitamin D ₂ or its derivative represented by In the presence, the 22,23-position is selectively oxidized to the corresponding 22,23-dihydroxy compound, and the 22,23-dihydroxy compound is then subjected to an oxidative cleavage reaction with an oxidizing agent to give a 20-formyl compound. And then further reducing the 20-formyl group with a reducing agent, a general formula [IV] (Wherein R ₁ , R ₂ and R ₃ have the same meanings as described above), and also relates to a method for producing a 22-seco derivative (hereinafter, sometimes referred to as the cleavage reduction method of the present invention).

Furthermore, the present invention has the general formula [II] [Wherein R ₁ , R ₂ and R ₃ have the same meanings as described above, R ₄ represents an aldehyde group or —CH ₂ OR ₅ (R ₅ represents a hydrogen atom or a hydroxy protecting group)] -A general formula [III] characterized by oxidizing a seco derivative with a metal oxide or a peroxide in an inert solvent. (In the formula, R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above,
R ₆ represents a hydrogen atom or a hydroxy protecting group) A method for producing 22,23-seco-1,7,8-trihydroxyvitamin D or a derivative thereof represented by the formula (hereinafter referred to as the hydroxy introduction method of the present invention) There is also).

The following compounds are known as the compound represented by the above general formula [I] used in the cleavage reduction method of the present invention.

That is, 7,8-dihydroxy-7,8-dihydrovitamin
D ₂ (R ₁ ＝ R ₂ ＝ R ₃ ＝ H) [Y.Wang, others, “Acta.Chim.S
in., "Vol. 24, P. 126, 1958" and the like are known.

In the cleavage reduction method of the present invention, as a first step, the compound represented by the above formula [I] is converted into a metal oxide such as osmium tetroxide in an inert solvent such as acetone or t-butanol. In the presence, selectively C (2
2), (23) Only the double bond is oxidized to the corresponding 22,23-dihydroxy compound, and then this dihydroxy compound is subjected to an oxidative cleavage reaction with an oxidizing agent such as metaperiodic acid soda acid to give C. A C (20) -formyl body, which is a (22), (23) -seco body, is further reduced by a reducing agent such as sodium borohydride to obtain a novel compound represented by the formula [IV]. You can get it. 22nd position in formula [IV]
The OH group can be converted into a protected hydroxyl group by a known method.

In the method of introducing hydroxy of the present invention, the compound of the present invention represented by the formula [II] is further added to a metal oxide such as selenium dioxide or peroxide in an inert solvent such as methylene chloride or acetonitrile. Allyl oxidation with an oxide or the like gives a novel compound represented by the formula [III].

This allyl oxidation gives a 1β-hydroxy compound as a main product together with a small amount of 1α-hydroxy compound, and this 1β-hydroxy compound is efficiently converted to the 1α-hydroxy compound by acetolysis of the corresponding mesylate compound. It

The compounds represented by the above formulas [II] to [IV] thus produced can be prepared by known methods (WHOkamura, others,
"J. Org. Chem." Vol. 48, P. 1414, 1983; or supra.
Y. Wang et al.) Oxidatively cleaves the 7,8-bond, which is one of the methods for synthesizing vitamin D derivatives. EGBaggiolini, others, "J.Org. Chem." Vol. 51,
P.3098, 1986; EG Baggiolini, others, Japanese Patent Application No. 59-5241
7; EG Baggiolini, others, Japanese Patent Application 60-22091; or above.
It can be said to be a very useful compound because it can be easily induced to a fragment corresponding to the A ring part or the C and D ring parts used in WHOkamura et al.).

<< Embodiment >> A concrete embodiment will be described below. FIG. 1 is an explanatory view of the whole process shown in FIG.
The asterisk * is a compound represented by the general formula [II], and the ● is a compound represented by the general formula [III].
I] and the compound represented by the general formula [III] are both
It is included in the novel compounds represented by the general formula [X].

Example 1 (1) 3β-O- (t-butyldimethylsilyl) -7,
8-dihydroxy-7,8-dihydroxyvitamin D ₂ 520mg
And 2,6-lutidine (400 mg) in dry methylene chloride (50 ml) under ice-cooling t-butyldimethylsilyl triflate (300 mg)
Is added dropwise with stirring.

The reaction solution was stirred at room temperature for 2 hours and then 50 ml of methylene chloride
After diluting with, wash with water, 10% hydrochloric acid, water, saturated sodium bicarbonate, and water in that order, and then dry with potassium carbonate.

The residue obtained after evaporation of the solvent was subjected to silica gel column chromatography [silica gel 10 g, solvent; n-hexane-acetic acid ethyl ester (100: 1 v / v)] to give 3β-O- (t
- obtaining butyldimethylsilyl)-7-(t-butyldimethylsilyloxy) -8-hydroxy-7,8-dihydro vitamin D ₂ 500 mg.

That is, the above reaction is represented by the following formula [step (1) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3500 NMR spectrum (CCl ₄ ) δ: 0.10 (6H, S), 0.12 (6H, S),
0.95 (9H, S), 0.95 (9H, S), 3.40 to 3.90 (1H, m), 4.90
(2H, brs), 5.00 (1H, d, J = 10Hz), 5.00-5.20 (2H,
m), 5.38 (1H, d, J = 10Hz) Mass spectrum (FD) m / e; 658 (M ⁺ ), 641,601,553,527,
509,438,391,383,382,381 (2) 3β-O- (t-butyldimethylsilyl) -7
- (t-butyldimethylsilyloxy) -8-hydroxy-7,8-dihydro vitamin D ₂ 100 mg and N- acetone 10ml methylmorpholine -N- oxide 30mg, in a mixture of water 1ml of osmium tetroxide catalyst weight t- Add 1 ml butanol solution and stir at room temperature for 13 hours.

After the reaction, a saturated acidic sodium sulfite solution is added, acetone is distilled off, and the resulting residue is extracted with methylene chloride.

The extract is washed successively with water, 10% hydrochloric acid, water, saturated sodium bicarbonate and water, and then dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 2 g, solvent; chloroform] to give 3β-O- (t-butyldimethylsilyl) -7-
(T-Butyldimethylsilyloxy) -8,22,23-trihydroxy-7,8,22,23-tetrahydrovitamin D ₂ 75 mg
To get

That is, the above reaction is as in the following equation [step (2) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3510 NMR spectrum (CCl ₄ ) δ: 0.06 (6H, S), 0.13 (6H, S),
0.90 (9H, S), 0.93 (9H, S), 3.20 ~ 3.90 (3H, m), 4.96
(2H, brs), 5.10 (1H, d, J = 10Hz), 5.30 (1H, d, J = 10H
z) Mass spectrum (FD) m / e; 692 (M ⁺ ), 690,672,656,648,
633,617,603,590,572 (3) 3β-O- (t-butyldimethylsilyl) -7
-(T-Butyldimethylsilyloxy) -8,22,23-trihydroxy-7,8,22,23-tetrahydrovitamin D ₂ 200
Excess sodium metaperiodate was added to a solution of 10 mg of methanol and 2 drops of water, and the mixture was stirred at room temperature for 2 hours.

The residue obtained by distilling off methanol is dissolved in methylene chloride, washed with water and dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 5 g, solvent; methylene chloride] to give 3β, 7-bis- (t-butyldimethylsilyloxy) -20 (S) -formyl-8. 150 mg of -hydroxy-9,10-secopregna-5 (Z), 10 (19) -diene are obtained.

That is, the above reaction is represented by the following formula [step (3) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3500,1710 NMR spectrum (CDCl ₃ ) δ: 0.07 (6H, S), 0.14 (6H,
S), 0.80 (3H, S), 0.87 (9H, S), 0.91 (9H, S), 1.07 (3
H, d, J = 9Hz), 3.50 to 3.90 (1H, m), 4.97 (2H, brs), 5.0
7 (1H, d, J = 10Hz), 5.35 (1H, d, J = 10Hz), 9.53 (1H, d,
J = 3Hz) Mass spectrum (FD) m / e; 590 (M ⁺ ), 575,549,533,474,
456,444,440,421 Example 2 (1) 3β-O- (t-butyldimethylsilyl) -7,
8-dihydrovitamin D ₂ 400 mg and 2,6-lutidine 640 mg
950 mg of t-butyldimethylsilyl triflate was added dropwise to a solution of 50 ml of dry methylene chloride in ice under cooling with ice.

The reaction solution was stirred at room temperature for 13 hours and then 50 ml of methylene chloride
Dilute with water, wash with water, 10% hydrochloric acid, water, saturated sodium bicarbonate, and water in that order, and dry with potassium carbonate.

The residue obtained after evaporation of the solvent was subjected to silica gel column chromatography [silica gel 10 g, solvent; n-hexane] to give 3β-O- (t-butyldimethylsilyl) -7,8-
Di - (t-butyldimethylsilyloxy) -7,8 obtain dihydro vitamin D ₂ 1 g.

That is, the above reaction is represented by the following formula [step (4) in FIG. 1].

NMR spectrum (CCl ₄ ) δ: 0.04 (9H, S), 0.07 (9H, S),
0.80 (27H, S), 3.40 ~ 4.00 (1H, m), 4.85 (2H, brs), 4.
95 (1H, d, J = 10Hz), 4.98 to 5.20 (2H, m), 5.40 (1H, d, J
= 10Hz) Mass spectrum (FD) m / e; 772 (M ⁺ ), 715,583,509,455,
391,392 (2) 3β-O- (t-butyldimethylsilyl) -7,
8-Di- (t-butyldimethylsilyloxy) -7,8-dihydrovitamin D ₂ 600 mg and N-methylmorpholine N
-To a mixed solution of 300 mg of oxide and 20 ml of acetone and 3 ml of water was added a 3 ml solution of t-butanol containing a catalytic amount of osmium tetroxide, and the mixture was stirred at room temperature for 13 hours.

After the reaction, a saturated acidic sodium sulfite solution is added, acetone is distilled off, and the resulting residue is extracted with methylene chloride.

The extract is washed successively with water, 10% hydrochloric acid, water, saturated sodium bicarbonate and water, and then dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 5 g, solvent; chloroform] to give 3β-O- (t-butyldimethylsilyl) -7,8.
-Di- (t-butyldimethylsilyloxy) -22,23-
Dihydroxy-7,8,22,23-tetrahydrovitamin D ₂ 500
get mg.

That is, the above reaction is represented by the following formula [step (5) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3500 NMR spectrum (CDCl ₃ ) δ: 0.09 (18H, S), 0.93 (27H,
S), 3.40 to 4.00 (3H, m) 4.95 (2H, brs), 5.03 (1H, d, J
= 10Hz), 5.47 (1H, d, J = 10Hz) Mass spectrum (FD) m / e; 772 (M ⁺ −34), 714,640,583,
509,455,391 (3) 3β-O- (t-butyldimethylsilyl) -7,
8-di- (t-butyldimethylsilyloxy) -22,23-
Dihydroxy-7,8,22,23-tetrahydrovitamin D ₂ 400
To a solution of 10 mg of methanol in 2 ml of water is added excess meta-periodic soda, and the mixture is stirred at room temperature for 2 hours.

The residue obtained by distilling off methanol is dissolved in methylene chloride, washed with water and dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 5 g, solvent; n-hexane-acetic acid ethyl ester (100: 1 v / v)] to give 3β, 7,8-tri- (t 250 mg of -butyldimethylsilyloxy-20 (S) -formyl-9,10-secopregna-5 (Z), 10 (19) -diene are obtained.

That is, the above reaction is represented by the following equation [step (6) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 1720 NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.92 (27H,
S), 3.40 to 4.00 (1H, m), 4.95 (2H, brs), 5.00 (1H, d, J
= 10Hz), 5.46 (1H, d, J = 10Hz), 9.53 (1H, d, J = 2.5H)
z) Mass spectrum (FD) m / e; 704 (M ⁺ ), 647,640,572,515,
339,323 (4) 3β, 7,8-Tri- (t-butyldimethylsilyloxy) -20 (S) -formyl-9,10-secopregna
To a mixed solution of 200 mg of 5 (Z), 10 (19) -diene in 10 ml of methanol and 5 ml of methylene chloride, 100 mg of sodium borohydride was added with stirring under ice cooling.

The reaction solution is stirred at room temperature for 1 hour.

The solvent is distilled off and the resulting residue is extracted with methylene chloride. The extract is washed with water and dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 2 g, solvent; n-hexane-acetic acid ethyl ester (100: 3 v / v)] to give 3β, 7,8-tri- (t -Butyldimethylsilyloxy) -20 (S)-
Hydroxymethyl-9,10-secopregna-5 (Z), 10
(19) -150 mg of dienes are obtained.

That is, the above reaction is represented by the following formula [step (7) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3600 NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.94 (27H,
S), 3.10 to 3.90 (3H, m), 4.95 (2H, brs), 5.00 (1H, d, J
= 10Hz), 5.46 (1H, d, J = 10Hz) Mass spectrum (FD) m / e; 706 (M ⁺ ), 649,574,517,455,
443,399,381 Example 3 (1) 3β, 7,8-tri- (t-butyldimethylsilyloxy) -20 (S) -hydroxymethyl-9,10-secopregna-5 (Z), 10 (19) -diene 1 g Then, a catalytic amount of p-toluenesulfonic acid was added to a solution of 180 mg of dihydropyran in 50 ml of methylene chloride under ice cooling, and the mixture was stirred at room temperature for 1 hour.

The reaction mixture is washed with saturated sodium bicarbonate solution and dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 10 g, solvent; n-hexane-acetic acid ethyl ester (100: 1 v / v)] to give 3β, 7,8-
Tri (t-butyldimethylsilyloxy) -20 (S)-
1 g of tetrahydropyranyloxymethyl-9,10-secopregna-5 (Z), 10 (19) -diene is obtained.

That is, the above reaction is represented by the following equation [step (8) in FIG. 1].

NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.90 (27H,
S), 3.20 to 4.00 (5H, m), 4.47 (1H, brs), 4.94 (2H, br
s), 5.00 (1H, dJ = 10Hz), 5.44 (1H, d, J = 10Hz) Mass spectrum (FD) m / e; 790 (M ⁺ ), 789,733,689,659,
649,633,601,557,511,497,483,455 (2) 3β, 7,8-tri- (t-butyldimethylsilyloxy) -20 (S) -tetrahydropyranyloxymethyl-9,10-secopregna-5 (Z), 10 (19) -diene 1
A suspension of g and 400 mg of selenium dioxide in 100 ml of methylene chloride and 10 ml of acetonitrile is heated under reflux for 16 hours with stirring.

The reaction solution is washed with 10% caustic soda water and water, and then dried with potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 10 g, solvent: n-hexane-acetic acid ethyl ester (100: 2 v / v)], and 3β, 7,8- was collected from the first fraction. Tri- (t-butyldimethylsilyloxy) -1α-hydroxy-20 (S) -tetrahydropyranyloxymethyl-9,10-secopregna-5
120 mg of (Z), 10- (19) -diene are obtained.

That is, the above reaction is represented by the following formula [step (9) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3600 NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.93 (27H,
S), 3.20 to 3.83 (5H, m), 4.40 (1H, brs), 4.50 (1H, br
s), 5.02 (1H, d, J = 10Hz), 5.17 (2H, brs), 5.70 (1H,
d, J = 10Hz) Mass spectrum (FD) m / e; 806 (M ⁺ ), 790,750,694,660,
543,510,481,438,409 From the second fraction, 3β, 7,8-tri- (t-butyldimethylsilyloxy) -1β-hydroxy-20 (S)-
683 mg of tetrahydroplanyloxymethyl-9,10-secopregna-5 (Z), 10 (19) -diene are obtained.

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 3600 NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.93 (27H,
S), 3.20 to 4.10 (6H, m), 4.50 (1H, brs), 5.03 (1H, d, J
= 10Hz), 5.10 (1H, brs), 5.31 (1H, brs), 5.60 (1H, d,
J = 10Hz) Mass spectrum (FD) m / e; 806 (M ⁺ ), 790,778,750,676,
511,481,439,410 (3) 3β, 7,8-tri- (t-butyldimethylsilyloxy) -1β-hydroxy-20 (S) -tetrahydropyranyloxy-9,10-secopregna-5 (Z), 10 (1
9) -diene 680 mg, pyridine 0.4 ml and catalytic amount of 4-
To a 50 ml solution of dimethylaminopyridine in methylene chloride, 150 mg of methanesulfonyl chloride was added dropwise with stirring under ice cooling.

The reaction solution is stirred for 30 minutes at room temperature, washed successively with water, 10% hydrochloric acid, saturated sodium bicarbonate solution and water, and dried over sodium sulfate.

The residue obtained by distilling off the solvent is immediately used in the next reaction without purification.

A suspension of 800 mg of the above mesylate and cesium acetate and 18-crown-6 (300 mg) in benzene (50 ml) was added to Dean-Star.
Heat under reflux for 16 hours under the device.

The reaction solution is washed with water and dried over sodium sulfate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silokagel 5 g, solvent; n-hexane-acetic acid ethyl ester (100: 2 v / v)], and 1α-acetoxy-3β, 7,8- Tri- (t-butyldimethylsilyloxy) -20 (S) -tetrahydropyranyloxymethyl-9,10-secopregna-5 (Z), 10 (19) -diene 500
get mg.

That is, the above reaction is represented by the following equation [step (10) in FIG. 1].

IR spectrum ν max (CHCl ₃ ) cm ⁻¹ : 1730 NMR spectrum (CCl ₄ ) δ: 0.07 (18H, S), 0.93 (27H,
S), 1.97 (3H, S), 3.30 ~ 4.20 (5H, m), 4.50 (1H, br
s), 5.10 (1H, d, J = 10Hz), 5.37 (1H, brs), 5.43 (1H, b
rs), 5.53 (1H, brs), 5.73 (1H, d, J = 10Hz) Mass spectrum (FD) m / e; 848 (M ⁺ ), 820,792,718,677,
497,439,410 (4) 1α-acetoxy-3β, 7,8-tri- (t-butyldimethylsilyloxy) -20 (S) -tetrahydropyranyloxymethyl-9,10-secopregna-5
To a solution of 480 mg of (Z), 10 (19) -diene in 50 ml of methylene chloride, 2 ml of 10% methanolic caustic soda solution was added and the mixture was allowed to stand at room temperature for 1
Stir for 5 hours.

After the reaction, the reaction solution is washed with water and dried over potassium carbonate.

The residue obtained by distilling off the solvent was subjected to silica gel column chromatography [silica gel 5 g, solvent; n-hexane-acetic acid ethyl ester (100: 2 v / v)] and, from the first fraction, 3β, 7,8. -Tri- (t-butyldimethylsilyloxy) -1α-hydroxy-20 (S) -tetrahydropyranyloxymethyl-9,10-secopregna-5
322 mg of (Z), 10 (19) -diene and 3β, 7,8-tri- (t-butyldimethylsilyloxy) -1β-hydroxy-20 (S) -tetrahydropyranyloxymethyl-9 from the second fraction, 10-Secopregna-5 (Z), 10
(19) -82 mg of dienes are obtained.

That is, the above reaction is represented by the following equation [step (11) in FIG. 1].

The identification of these performance products was confirmed by the fact that the data obtained by the various instruments completely matched the authentic product obtained in Example 3 (2).

<< Effects of the Invention >> The compound of the present invention represented by the general formula [X] is a novel substance as described above, and can provide an extremely useful substance as vitamin D as described above.

According to the cleavage reduction method of the present invention, the novel substance according to the present invention can be easily obtained by selectively cleaving the C (22) and (23) bonds of 7,8-dihydroxyvitamin D ₂ or its derivative molecule. You can

According to the hydroxy introduction method of the present invention, selective C (2
2), (23) Cleavage reaction and allyl oxidation give C (1)
By directly attaching one oxygen functional group to the position, an effective new substance can be provided epoch-making efficiently.

[Brief description of drawings]

 FIG. 1 is an explanatory diagram of the overall steps of the method of the present invention.

Claims (3)

[Claims] 1. A general formula [X] [In the formula, R ₁ , R ₂ and R ₃ represent the same or different hydrogen atoms or a hydroxy protecting group, R ₄ represents an aldehyde group or —CH ₂ OR ₅ (R ₅ represents a hydrogen atom or a hydroxy protecting group), X represents a hydrogen atom, a hydroxy group or a derivative group thereof]. 2. A general formula [I] (In the formula, R ₁ , R ₂ and R ₃ represent the same or different hydrogen atom or hydroxy protecting group) 7,8-dihydroxyvitamin D ₂ or its derivative represented by In the presence, the 22,23-position is selectively oxidized to the corresponding 22,23-dihydroxy compound, and the 22,23-dihydroxy compound is then subjected to an oxidative cleavage reaction with an oxidizing agent to give a 20-formyl compound. And then further reducing the 20-formyl group with a reducing agent, a general formula [IV] (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as described above). 3. General formula [II] [In the formula, R ₁ , R ₂ and R ₃ represent the same or different hydrogen atom or a hydroxy protecting group, R ₄ represents an aldehyde group or -CH ₂ OR ₅ (R ₅ represents a hydrogen atom or a hydroxy protecting group)] The 22-seco derivative represented by the general formula [III] characterized by being oxidized with a metal oxide or a peroxide in an inert solvent. (In the formula, R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above,
R ₆ represents a hydrogen atom or a hydroxy protecting group), and a method for producing 22,23-seco-1,7,8-trihydroxyvitamin D or a derivative thereof.