JP3415877B2 - 22-oxavitamin D derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] The present invention relates to a novel 22-oxabi compound.
It relates to a Tamine D derivative. The compounds of the present invention
Has a growth inhibitory effect and a differentiation inducing effect of a drug, for example,
It is useful as a tumor agent and a psoriasis treatment. [0002] 2. Description of the Related Art In recent years, the physiological activity of vitamin D
It has been revealed gradually. Vitamin Ds, for example,
1α, 25-dihydroxyvitamin D₃Is the calcium bill
The effect of regulating tumors, the effect of inhibiting the growth of tumor cells, etc.
Have a wide variety of physiological activities, such as
And is known. [0003] However, 1α, 25-dihydroxybi
Tamin D₃Has high calcium due to long-term and continuous administration
Have the drawback of causing mumemia, such as antitumor
It is not suitable for use as an agent or an antirheumatic agent. others
Recently to separate the action of these vitamin Ds
Many vitamin D derivatives have been synthesized and their physiological activities
Are being considered. One of them is disclosed in Japanese Patent Application Laid-Open No. 61-267.
No. 550, 1α, 3β-dihydroxy
-20 (S)-(3-hydroxy-3-methylbutylo)
Xy) -9,10-secopregna-5,7,10 (1
9)-There is a triene. The inventor has found that similar compounds
As a result of various studies on 22-oxavitamin Ds,
Among 26-hydroxy-22-oxavitamin Ds,
That there is a compound that has a strong differentiation-inducing effect on tumor cells, etc.
I found it. The present invention has been completed based on this finding.
It is. The present invention provides a compound represented by the following general formula (I):
Oxavitamin D derivatives. Embedded image (Where R₁, R₂Represents a hydrogen atom or a hydroxyl group.
Where R₁Is a hydrogen atom, R₂Represents a hydroxyl group;
₁When R is a hydroxyl group,₂Represents a hydrogen atom. ) All of these compounds of the present invention are novel
And described, for example, in JP-A-61-267550.
Of 1α, 3β-bis (tert-butyldimethylsilyl)
Oxy) -pregna-5,7-diene-20 (S) -O
(II) as a starting material. The following
An example of the method is shown. [0007] Embedded image Compounds of formula (XV) in the presence of a base in a compound of formula (II)
React to give a compound of formula (III). The formula (X
The compound of V) is obtained, for example, as follows. Embedded imageThat is, after protecting the hydroxyl group of allyl alcohol, 2
The compound of the formula (X) obtained by oxidizing the heavy bond with ozone
To give the compound of formula (XI). Then, the formula (X
The compound of I) is reduced with diisobutylaluminum hydride.
After converting to alcohol form (XII), the hydroxyl group was
Protection gives the compound of (XIII). Water protected earlier
The acid group is selectively deprotected, and the hydroxyl group is
To give the compound of formula (XV). The compound of formula (III) has a pyridinium para
By reacting with toluenesulfonate, etc., 1
Deprotection leaving only the protection of the hydroxyl group at the position of formula (IV)
Get the compound. Sharpless oxidation of a compound of formula (IV)
To obtain epoxy compound (V) stereoselectively by
Can be. The obtained epoxy compound (V) is diisobutyric
Ring opening and deprotection with aluminum hydride
Yields a compound of formula (VII). Formula (VII)
Following the conventional method, the compound of
To obtain the compound (I) of the present invention.
it can. [0010] Next, an embodiment of the present invention will be described.
The invention is not limited. [0011] [Reference Example 1]3-tert-butyldimethylsilyloxy-1-propene
Synthesis Allyl alcohol (8.16 ml, 120 mmol),
tert-butyl (chloro) dimethylsilane (15.0
g, 100 mmol), triethylamine (50.2 m
1,360 mmol), 4-dimethylaminopyridine
(1.47 g, 12 mmol) in dichloromethane (25
4 ml) and stirred at room temperature for 20 hours. reaction
The solution was diluted with diethyl ether (hereinafter Et₂O) diluted with water,
Ice-cooled 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution
(Hereinafter referred to as saturated weight), washed with saturated saline,
Cium (hereinafter MgSO)₄), And evaporate the solvent under reduced pressure
You. The residue was distilled under reduced pressure (bp 49-50 ° C, 16 mmH
g) to give a clear oil (IX) (13.79)
g, 80.2%). IR (neat) cm^-1: 1254, 1
007,918;¹ H-NMR (90 MHz, CDCl₃) Δ: 6.09
-5.73 (1H, m), 5.38-5.01 (2H,
m), 4.17 (2H, dt, J = 1.71, 4.4H
z), 0.91 (9H, s), 0.07 (6H, s); MS m / z: 172 (M⁺); Exact mass calcd for C₉H
₂₀OSi 172.1283. Found 172.
1258. [0013] [Reference Example 2]4-tert-butyldimethylsilyloxy-2-methyl-2
-Synthesis of butenoic acid ethyl ester With the ether form (IX) (1 g, 5.8140 mmol)
Sodium bicarbonate (1.15 g, 13.69 mmol
l) is suspended in dichloromethane (60 ml) and
Keep at ° C. Ozone gas was passed through this reaction solution for 45 minutes.
Thereafter, nitrogen gas is introduced for 30 minutes. There triphenyl
Phosphine (2.3 g, 8.721 mmol) was added,
Stir for 1 hour at room temperature. By these operations, the reaction solution
An aldehyde (X) is obtained in the reaction,
This was used in the next reaction without purification. [0014] The reaction solution (carboethoxyethylide)
) Triphenylphosphorane (4.88 g, 12.79)
mmol) and stir at room temperature overnight. Dissolution of reaction solution
After evaporating the medium under reduced pressure, extract with hexane and remove with a glass filter.
And filtered. The solvent of the filtrate was distilled off under reduced pressure, and the residue was
Kagel column chromatography [SiO₂100g,
Et₂O: n-hexane = 1: 20 (v / v)]
And conjugated ester (XI) (1.2703 g, 84%)
Is obtained as a clear oil. IR (neat) cm^-1: 1715, 1
243;¹ H-NMR (90 MHz, CDCl₃) Δ: 6.76
(1H, brt, J = 5.6 Hz), 4.33 (2H,
brd, J = 5.6 Hz) 4.19 (2H, q, J =
7.1 Hz), 1.79 (3H, brs), 1.28
(3H, t, J = 7.1 Hz), 0.90 (9H,
s), 0.08 (6H, s); MSm / z = 258 (M⁺); Exact mass calcd for C₁₃H
₂₆O₃Si: 258.11651. Found 25
8.1661. [0016] [Reference Example 3]4- (tetrahydropyran-2-yloxy) -3-me
Synthesis of tyl-2-buten-1-ol [0017] Reference Example 3 Conjugated ester (XI) kept at -74 ° C
(1.22 g, 4,729 mmol) in dichloromethane
Diisobutylaminium hydride in solution (27 ml)
(Hereinafter referred to as DIBAH) 1M toluene solution (2.53
ml, 14.19 mmol) and stir for 45 minutes
You. A 10% aqueous sodium hydroxide solution (0.
72 ml), and slowly raise the temperature to room temperature for 1 hour.
Stir for 20 minutes. This solution is CH₂Cl₂And THF
The solution was filtered through Celite as an extraction solvent, and the filtrate was dried over MgSO 4.₄
And dried under reduced pressure to remove the solvent under reduced pressure to give the alcohol (XII)
(1.12 g) was obtained. This product can be used without purification
Used for the operation. Crude alcohol (XII) (1.12 g)
CH₂Cl₂Pyridinium palat in solution (11 ml)
Luene sulfonate (hereinafter referred to as PPTS) (119m
g, 0.4729 mmol) and dihydropyran (1.7
5 ml, 18.92 mmol) for 3 hours 35 minutes
Stir under warm. Two-thirds of the solvent of the reaction solution was reduced at room temperature under reduced pressure.
Distill, Et₂After dilution with O, wash with water. MgSO₄
And dried under reduced pressure to remove the solvent under reduced pressure.
I) (1.59 g) was obtained. Do not purify this
Used for the next reaction. The crude diether compound (XIII) (1.59)
g) in THF solution (47 ml)
Umfluoride (hereinafter referred to as TBAF) (1 mol /
1THF, 5.7 ml, 5.7 mmol) and add room temperature
Stir under for 20 minutes. Furthermore, TBAF (1.42 ml,
1.42 mmol) and stirred for 15 minutes.
F (1.42 ml, 1.42 mmol) was added and stirred for 15 minutes.
Mix. This reaction solution is₂Diluted with O, water and saturated salt
After washing with water, MgSO₄And evaporate the solvent under reduced pressure
You. The residue was subjected to silica gel column chromatography [Si
O₂70g, Et₂O: n-hexane = 2: 1 (v /
v)], the alcohol (XIV) (735 mg,
83.6%) as a clear oil. IR (neat) cm^-1: 3402,8
68,812; 1H-NMR (90 MHz, CDCl₃) Δ: 5.64
(1H, dt, J = 1.2, 6.8 Hz), 4.58
(1H, drt), 4.32 to 3.27 (6H, m),
2.12 (1H, brt), 1.96 to 1.20 (6
H, m), 1.66 (3H, s); MS m / z: 155 (M⁺-CH₂OH): Exact mass calcd for C₉H
_FifteenO₂155.1072. Found 155.10
87; Anal. Calcd for C₁₀H₁₈O₃:
C, 64.47; H, 9.75. Found: C, 6
4.16; H, 9.83. [0022] [Reference Example 4]4- (tetrahydropyran-2-yloxy) -3-me
Synthesis of tyl-2-butene-1-bromide Alcohol (XIV) (650 mg,
3.495 mmol) in dichloromethane (40 m
l) to triphenylphosphine (1.1 g, 4.194)
mmol) Cobalt tetrabromide (1.74 g) 5.242 mm
ol), sodium hydrogen carbonate (881 mg, 10.49)
mmol) and stirred at room temperature for 4 hours. Reaction mixture
Dilute with dichloromethane and wash with saturated heavy water and saturated saline
Pure, MgSO₄After drying in 4, the solvent is distilled off under reduced pressure. Remaining
The residue is subjected to silica gel column chromatography [SiO₂1
0g, Et₂O: n-hexane = 1: 5 (v / v)]
When attached, the bromo compound (XV) (514.6 mg, 59.1)
%) Is obtained as a clear oil. IR (neat): 1121, 663;¹ H-NMR (90 MHz, CDCl₃): 5.83
(1H, brt, J = 7.9 Hz), 4.60 (1H,
brt), 4.33-3.34 (6H, m), 1.74.
(3H, s), 2.09-1.14 (6H, m); MS m / z: 247 (M⁺-H⁺); Exact mass calcd forC₁₀H
₁₆O₂Br 247.0334. Found 24
7.0346. [0025] [Reference Example 5]1α, 3β-bis (t-butyldimethylsilyl)
Ryloxy) -20 (S)-(3-methyl-4-tetra
Hydropyranyloxy) -2 (E) -butenyloxy-
Synthesis of 5,7 dienes 1α, 3β-bis (t-butyldimethylsiloxane)
Ryloxy) -20 (S) -hydroxypregna-5,
7-diene (II) (300 mg, 0.5357 mmol
l) in a THF solution (10 ml) of potassium hydride under ice-cooling
(64.3 mg, 1.607 mmol) at room temperature
Stir for 1 hour 30 minutes. Bromo compound (XV) (267 m
g, 1.071 mmol) in a THF solution (11 ml).
Then, the mixture is heated to 80 ° C. and stirred for 1 hour and 20 minutes. This anti
The reaction solution was returned to room temperature, and the reaction was stopped with water.₂In O
Dilute, wash with brine, MgSO₄And dried under reduced pressure
The lower solvent is distilled off. The residue is purified by silica gel column chromatography.
Raffy [SiO₂50g Et₂O: n-hexane =
1:10, 1: 3 (v / v)], the ether form
(III) (196.7 mg, 50.4%)
Obtained as an oil. IR (neat) cm^-1: 2934, 1
253, 1077, 1022, 835;¹ H-NMR (90 MHz, CDCl₃): 5.74-
5.25 (3H, m), 4.75 (1H, bt), 4.
27-3.21 (9H, m), 1.19 (3H, d, J
= 7.0Nz), 0.87 (21H, s), 0.60
(3H, s), 0.11 (6H, s), 2.81-0.
11 (24H, m), 0.06 (6H, s) MS m / z: 728 (M⁺) Exact mass calcd for C₄₃H
₇₆O₅Si₂728.5232. Found 72
8.5230. [0028] [Reference Example 6]1α-t-butyldimethylsilyloxy-3β-hydro
Xy-20 (S)-(4-hydroxy-3-methyl-2
(E) -Butenyloxy) pregna-5,7-diene
Synthesis The ether compound (III) (668.8 mg,
0.9187 mmol) in methanol (8.4 m
l) to PPTS (78.5 mg, 0.3124 mmol)
1) and stirred at room temperature for 26 hours and 20 minutes. This reaction
Dilute the solution with dichloromethane, extract and wash with saturated saline
Pure, MgSO₄After drying with, the solvent is distilled off under reduced pressure. Residue
To silica gel column chromatography [SiO₂32
gEt₂O: n-hexane = 2: 1 (v / v)]
And diol form (IV) (399.8 mg, 82.4)
%) Is obtained as a transparent foam. IR (neat) cm^-1: 3366,1
255, 1147, 1086, 836;¹ H-NMR (90 MHz, CDCl₃): 5.74-
5.25 (3H, m), 4.27 to 3.21 (7H,
m), 1.19 (3H, d, J = 6.1 Hz), 0.8
7 (12H, s), 0.60 (3H, s), 0.11
(3H, s), 2.81 to 0.11 (20H, m),
0.06 (3H, s); MS m / z: 530 (M⁺); Exact mass calcd for C₃₂H
₅₄O₄Si 530.3792. Found 53
0.3820; Anal. Calcd forC₃₂H
₅₄O₄Si C, 72.40; H, 10.26. Fo
und: C, 72.50; H, 10.21; [Α]_D ³⁰−7.67 (c = 1.622, CHC
l₃). [0031] [Reference Example 7]1α-t-butyldimethylsilyloxy-3β-hydro
Xy-20 (S)-[2 (S), 3 (R) -epoxy-
4-hydroxy-3-methylbutyloxy] pregna-
Synthesis of 5,7-diene At -25 ° C., (+)-L-tartrate
Isopropyl (123.4 mg, 0.5268 mmol
l) Diclo of 4Å molecular sieves (55mg)
Methane suspension (6.9 ml) in titanium (IV)
Trisopropoxide (0.14ml, 0.4703m
mol) and stirred for 10 minutes. Aliquots for this reaction
Alcohol (IV) (170 mg, 0.3220 m
mol) in dichloromethane solution (6.9 ml) and t-
Butyl hydroperoxide (1.04 mol / 1,
0.69 ml, 0.7176 mmol) at the same temperature
Add to the solution and stir for 2 hours 10 minutes. 10%
Tartaric acid (0.82 ml) was added at the same temperature and stirred for 30 minutes.
Heat to room temperature. Dilute the reaction solution with dichloromethane
And filter through celite. Wash the filtrate with saturated heavy water, M
gSO₄And the solvent is distilled off under reduced pressure. Silica residue
Gel column chromatography [SiO₂8g, Et₂
O: n-hexane = 5: 1 (v / v)]
Cid form (Va) (150.5 mg, 85.9%) is transparent
Obtained as an oily substance. [Α]_D ³⁰-16.72 (c = 1.91
8, CHCl₃); IR (neat) cm^-1: 3400, 1254, 11
47, 1086, 1064, 867, 833, 812,
770;¹ H-NMR (300 MHz, CDCl₃): 5.63
(1H, brd, J = 6.8 Hz), 5.33 (1H,
brd, J = 6.8 Hz), 4.06 (1H, br)
s), 3.77 to 3.22 (8H, m), 2.80 (1
H, brs), 2.50 (1H, brd, J = 13.6)
Hz), 2.31 (1H, brt, J = 13.6H)
z), 2.09-1.87 (4H, m), 1.79-
0.96 (9H, m), 1.60 (3H, s), 1.3
1 (3H, s), 1.19 (3H, d, J = 5.9H
z), 0.88 (9H, s), 0.63 (3H, s),
0.12 (3H, s), 0.07 (3H, s); MS m / z: 546 (M⁺); Exact mass calcd for C₃₂H
₅₄O₅Si 546.3741. Found 54
6.3720. [0034] [Reference Example 8]1α-t-butyldimethylsilyl quinone-3β-hydro
Xy-20 (S)-[2 (R), 3 (S) -epoxy-
4-hydroxy-3-methylbutyloxy] pregna-
Synthesis of 5,7-diene At -25.degree. C., (-)-D-tartaric acid
Isopropyl (123.4 mg, 0.5268 mmol
l) Diclo of 4Å molecular sheep (55mg)
Methane suspension (6.9 ml) in titanium (IV)
Trisopropoxide (0.14ml, 0.4703m
mol) and stirred for 10 minutes. Aliquots for this reaction
Alcohol (IV) (170 mg, 0.3220 m
mol) in dichloromethane solution (6.9 ml) and t-
Butyl hydroperoxide (1.04 mol to 1,
0.69 ml, 0.7176 mmol) at the same temperature
Add to the solution and stir for 2 hours 10 minutes. 10%
Tartaric acid (0.82 ml) was added at the same temperature and stirred for 30 minutes.
Raise the temperature to warm. Dilute the reaction with dichloromethane and
Filter by light. Wash the filtrate with saturated aqueous sodium bicarbonate, MgSO
₄And the solvent is distilled off under reduced pressure. Silica gel residue
Ram chromatography [SiO₂8g, Et₂O: n
-Hexane = 5: 1 (v / v)] to give an epoxide
(Vb) (156.2 mg, 89.2%) is a clear oil
Obtained as a substance. [Α]_D ³¹-1.76 (c = 1.45)
2, CHCl₃); IR (neat) cm^-1: 3404, 1255, 11
47,1087,1066,868,834,812,
770;¹ H-NMR (300 MHz, CDCl₃): 5.61
(1H, brd, J = 6.8 Hz), 5.33 (1H,
brd, J = 6.8 Hz), 4.07 (1H, br)
s), 3.81 to 3.19 (8H, m), 2.80 (1
H, brs), 2.49 (1H, brd, J = 13.6)
Hz), 2.29 (1H, brt, J = 13.6H)
z), 2.09-1.86 (4H, m), 1.77-
0.63 (9H, m), 1.59 (3H, s), 1.3
1 (3H, s), 1.21 (3H, d, J = 6.0H
z), 0.88 (9H, s), 0.61 (3H, s),
0.11 (3H, s), 0.07 (3H, s); MS m / z: 546 (M⁺); Exact mass calcd for C₃₂H
₅₄O₅Si 546.3741. Found 54
6.3734. [0037] [Reference Example 9]1α, 3β-dihydroxy-20 (S)-[3 (R),
4-dihydroxy-3-methylbutyloxy] pregna
Synthesis of -5,7-diene DIBAH (1.58 ml, 1.58 mm
ol) was converted to the epoxide form (Va) (145 mg, 0.26
65 mmol) in toluene solution (3.3 ml) at 0 ° C
After stirring for 2.5 hours, DIBAH (1 m
1, 1 mmol) and stirred for 1 hour and 20 minutes. This anti
10% aqueous sodium hydroxide solution (0.66 ml)
And an appropriate amount of THF, and the mixture was heated to 60 ° C and stirred for 30 minutes.
I do. The reaction mixture was diluted with dichloromethane and THF as the extraction solvent.
Filter by light and filter the filtrate with MgSO₄After drying with
Upon distillation, triol (VIa) (136.8 mg) is obtained.
can get. This is used for the next reaction without purification.
Was. Crude triol (VIa) (135 mg,
0.2473 mmol) in a THF solution (10 ml).
BAF (1 mol / 1 THF: 0.74 ml, 0.74
mmol) and stir overnight at reflux. reaction
Dilute the solution with ethyl acetate and add water, 10% HCl aqueous solution,
After washing with saturated sodium bicarbonate saturated with salt, MgSO₄Dry
Dry and evaporate the solvent under reduced pressure. Silica gel column residue
Chromatography [SiO₂10 g, MeOH: CHC
l₃= 1: 20 (v / v)], the tetraol form
(VIIa) (83.0 mg, 77.3%) as colorless crystals
Was obtained as [Α]_D ²⁹-14.65 (c = 1.28)
8, CH₃OH); IR (neat) cm^-1: 3372, 2934, 28
74, 1647, 1054;₁ H-NMR (500 MHz, CDCl₃): 5.73
(1H, dd, J = 2.4, 5.5 Hz), 5.40
(1H, dd, J = 2.4, 5.5 Hz), 4.10
4.02 (1H, m), 3.79 to 3.74 (2H,
m), 3.55 (1H, dt, J = 3.1, 9.3H
z), 3.46-3.37 (2H, m), 3.29 (1
H, quint, J = 7.0 Hz), 2.76 to 2.6.
8 (1H, m), 2.64 (1H, brs), 2.54
(1H, ddd, J = 1.8, 2.4, 7.0 Hz),
2.34 (1H, brt, J = 7.0 Hz), 2.14
(1H, dq, J = 2.4, 7.0 Hz), 2.06-
1.86 (4H, m), 1.79-1.39 (12H,
m), 1.21 (3H, d, J = 6.1 Hz), 1.2
0 (3H, s), 1.01 (3H, s), 0.62 (3
H, s); MS m / z: 434 (M⁺); Exact mass calcd for C₂₆H
₄₂O₅434.303032. Found 434.30
21. [0041] [Reference Example 10]1α, 3β-dihydroxy-20 (S)-[3 (S),
4-dihydroxy-3-methylbutyloxy] pregna
Synthesis of -5,7-diene DIBAH (2.32 ml, 2.32 mm
ol) with the epoxide form (Vb) (150 mg, 0.27
57 mmol) in toluene solution (3.4 ml) at 0 ° C
After stirring for 2 hours 30 minutes, DIBAH (0.
5 ml, 0.5 mmol) and stir for 1 hour and 20 minutes
You. A 10% aqueous sodium hydroxide solution (0.
68 ml) and an appropriate amount of THF.
Stir for 30 minutes. The reaction solution was extracted with dichloromethane and THF.
The solvent was filtered through celite, and the filtrate was dried over MgSO 4.₄After drying in
When the solvent was distilled off under reduced pressure, triol (VIb) (123.
8 mg) are obtained. It can be purified without purification
Was used for the reaction. Crude triol (VIb) (122 mg,
0.2234 mmol) in a THF solution (9 ml).
AF (1 mol / 1 THF: 0.67 ml, 0.67 m
mol) and stirred at reflux overnight. Reaction liquid
Was diluted with ethyl acetate, and water, 10% aqueous HCl, and sodium chloride were added.
After washing with saturated heavy water saturated with₄Dry
Then, the solvent is distilled off under reduced pressure. The residue is purified by silica gel column chromatography.
Matography [SiO₂10 g, MeOH: CHCl
₃= 1: 20 (v / v)], the tetraol form
(VIIb) (83.8 mg, 86.4%) as colorless crystals
Was obtained as [Α]_D ²⁹-14.73 (c = 1.11
6, CH₃OH); IR (neat) cm^-1: 3380, 2936, 16
49, 1052;¹ H-NMR (500 MHz, CDCl₃): 5.73
(1H, dd, J = 2.4, 5.5 Hz), 5.40
(1H, dd, J = 2.4, 5.5 Hz), 4.06
(1H, sextet, J = 6.1 Hz), 3.88
(1H, dt, J = 3.1, 9.3 Hz), 3.77
(1H, brs), 3.46 (1H, brd, J = 1)
1.0 Hz), 3.43 to 3.34 (2H, m),
34 to 3.26 (1H, m), 2.96 (1H, br)
s), 2.78 to 2.69 (1H, m), 2.53 (1
H, ddd, J = 1.8, 2.4, 15.9 Hz),
2.34 (1H, brt, J = 7.0 Hz), 2.14
(1H, dq, J = 2.4, 13.1 Hz), 2.04
To 1.85 (4H, m), 1.79 to 1.24 (12
H, m), 1.22 (3H, d, J = 6.1 Hz),
1.18 (3H, s), 0.94 (3H, s), 0.6
1 (3H, s); MS m / z: 434 (M⁺); Exact mass calcd for C₂₆H
₄₂O₅434.303032. Found 434.30
07. [0045] Embodiment 11α, 3β-dihydroxy-20 (S)-[3 (R),
4-dihydroxy-3-methylbutyloxy] -9,1
0-Secopregna-5,7,10 (19) -triene
Synthesis 1α, 3β-dihydroxy-20 (S)-
[3 (R), 4-dihydroxy-3-methylbutyloxy]
B) Pregna-5,7-diene (VIIa) 22.7 m
g in 20 ml of ethanol, and
400W high-pressure mercury lamp-Bico
Light irradiation for 2 minutes and 35 seconds using a
Heat reflux. The residue obtained by distilling off the solvent under reduced pressure
Chromatography (silica gel, ethanol: acetic acid
(Chill = 1: 25, developed twice)), and then refined.
Chromatography (silica gel, dichloromethane: eta
(Nol = 20: 3) to give the title compound as a colorless oil
(4.1 mg) was obtained. IR (neat) cm^-1: 3385 (b
load), 2920, 2865, 1050, 730.¹ H. NMR δ: 6.37 (1H, d, J = 11.
2Hz), 6.02 (1H, d, J = 11.2Hz),
5.33 (1H, s), 5.00 (1H, s), 4.4
3 (1H, brs), 4.22 (1H, brs) 3.6
9 to 3.81 (1H, m), 3.44 to 3.61 (1
H, m), 3.42 (2H, s), 3.21 to 3.34.
(1H, m), 1.19 (3H, s), 1.19 (3
H, d, J = 5.9 Hz), 0.54 (3H, s); MS (m / z): 434 (M⁺), 85 (100%); UV (EtOH) λ max nm: 264 min
nm: 227; [Α]_D65.85 (c = 0.082, EtOH). [0048] Embodiment 2 1α. 3β-dihydroxy-20 (S), [3 (S),
4-dihydroxy-3-methylbutyloxy] -9,1
0-Secopregna-5,7,10 (19)-Lien's
Synthesis 1α, 3β-dihydroxy-20 (S)-
[3 (S), 4-dihydroxy-3-methylbutyloxy
B) Pregna-5,7-diene (VIIb) 20.1 m
g in 20 ml of ethanol, and
400W high-pressure mercury lamp-Bico
Light irradiation for 2 minutes and 35 seconds using a
Heat reflux. The residue obtained by evaporating the solvent under reduced pressure is a thin layer for preparative separation.
Chromatography (silica gel, ethanol: acetic acid
(Chill = 2:25, developed twice))
Chromatography (silica gel, dichloromethane: eta
(Nol = 20: 3) to give the title compound as a colorless oil
(3.9 mg) was obtained. IR (neat) cm^-1: 3375 (b
load), 2920, 2865, 1050;¹ H-NMR δ: 6.37 (1H, d, J = 11.6)
Hz), 6.02 (1H, d, J = 11.6 Hz),
5.33 (1H, s), 4.99 (1H, s), 4.4
2 (1H, brs), 4.23 (1H, brs),
81-3.93 (1H, m), 3.57 (1H, s),
3.25 to 3.50 (3H, m), 1.20 (3H,
d, J = 7.3 Hz), 1.18 (3H, s), 0.5
3 (3H, s) MS (m / z): 434 (M⁺), 85 (100%); UV (EtOH) λ max nm: 263 min
nm: 227; [Α]_D49.35 (c = 0.077, EtOH).

──────────────────────────────────────────────────の Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 401/00 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] General formula (I) (In the formula, R ₁ and R ₂ represent a hydrogen atom or a hydroxyl group.
Provided that when R ₁ is a hydrogen atom, R ₂ represents a hydroxyl group;
_{When 1} is a hydroxyl group, R ₂ represents a hydrogen atom. A) 22-oxavitamin D derivative;