JPS6144880B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides 24ξ・25-dihydroxycholester
1,4,6-trien-3-one (hereinafter 24ξ・25
-dihydroxy-trienone). This compound is useful as an intermediate in the production of 1,24ξ,25-trihydroxycholecalciferol or 24ξ,25-dihydroxycholecalciferol, which are analogs of active vitamin _D3 . As a method for producing 24ξ・25-dihydroxy-trienone, the conventional method starting from fucosterol by Ikegawa et al. [Chem.Pharm, Bull.Japan, 23
(3), 695-697 (1975)] is known. This method requires only 8 steps and has a relatively good yield, but it requires a rather laborious operation to extract fucosterol from a type of seaweed such as Kajime. The problem is that it is difficult to obtain large quantities of the raw material fucosterol. The present inventors have developed an efficient method using lithocholic acid, which is available in large quantities and at low cost in high purity, as a starting material.
We have discovered a method for producing ξ25-dihydroxy-trienone. The reaction formula of the method of the present invention is as follows: That is, lithocholic acid (2) is esterified with a lower alkanol such as methanol or ethanol in the presence of a dehydration catalyst such as p-toluenesulfonic acid to obtain an ester (2). Then, the ester (2) is oxidized with Johns reagent to obtain the keto ester (2). Then, the ketoester () was converted into 2-methyl-
Ketalization is performed with 2-ethyl-1,3-dioxolane to obtain a ketal ester (). Then, the ketal ester () is reduced with lithium aluminum hydride to obtain the ketal alcohol (). Then, the ketal alcohol () is oxidized with pyridinium chlorochromate to obtain the ketal aldehyde (). Then, the ketalaldehyde () is treated with a triphenylphosphine isopropylidene reagent to obtain the 24-ene (). Then, the 24-ene body ( ) is oxidized with an organic peracid such as m-chloroperbenzoic acid to obtain the 24·25-epoxy body ( ). Then, the 24.25-epoxy compound () is hydrolyzed with an acid such as sulfuric acid to obtain the 24ξ.25-diol compound (). Then, an acylating agent such as acetic anhydride is used on the 24ξ·25-diol body ( ) at room temperature to obtain a 24ξ-ol-25-acyloxy body ( ). Then, the 24ξ-ol-25-acyloxy compound () is treated with an acylating agent such as acetic anhydride while heating to obtain the 24ξ.25-diacyloxy compound (XI). Then, the 24ξ·25-diacyloxy compound (XI) is oxidized with 2,3-dichlorodi-5,6-cyanobenzoquinone to obtain the dienone compound (XII). Then, the dienone compound (XII) was dehydrogenated with chloranil in the presence of 1,2-dihydro-2,3-dichlorodi-5,6-cyanobenzoquinone to give 24ξ·25
- Obtain diacyloxytrienone compound (). Finally, the 24ξ・25-diacyloxy-trienone compound () is subjected to alkaline hydrolysis to obtain the target compound 24
ξ·25-dihydroxy-trienone () is obtained. According to the present invention, starting from lithocholic acid, 24ξ.25-dihydroxy-cholester-1.4.6-trien-3-one is obtained with an overall yield of about 5.5% or more. Formulas () to () in the method of the present invention
All of the intermediate compounds are new substances that have not been described in any literature. The invention is further illustrated in the following examples. Example 1 (1) Methyl 3α-hydroxy-5β-cholane-
Production of 24-oate () 600 g of lithocholic acid, 4.0 g of p-toluenesulfonic acid monohydrate and 2.5 g of methanol
The mixture was placed in a 4-necked flask, and heated under reflux for 3 hours while stirring. The resulting yellow solution was cooled to 20 °C and
The precipitated product () was collected. white columnar crystals
515.9g; mp131-3℃ By adding water to the mother liquor, the target product ()
An additional 92.9 g was obtained. Target yield: 608.8g (yield 97.8%) IR spectrum ( _νnujiolnax ): 3540cm ^-1
(OH)1710cm ^-1 (C=O) (2) Production of methyl 3-oxo-5β-cholan-24-oate () Methyl-3α-hydroxy-obtained in Example 1
5β-cholan-24-oate () 300.0g
(0.07M), 1.5% of tetrahydrofuran, and 0.5% of acetone were placed in a 5-volume 4-necked flask, cooled on ice (inner temperature: 2-6°C) and stirred, and mixed with 346ml of Jones's reagent (0.78M) [67.2ml of concentrated sulfuric acid,
Prepared from 280ml of water and 78.3g of chromium trioxide]
was added dropwise over 70 minutes. After the completion of the dropwise addition, the reaction mixture was stirred at the same temperature for 60 minutes, and then allowed to stand at room temperature, and the precipitated pale yellow crystals () were collected. 193.0g; mp120-21℃. 75.2 g of the target product ( ) was further separated from the mother liquor. Target yield: 268.2g (yield 89.8%) IR spectrum ( _νnudjolnax ): 1730, 1705
cm ^-1 (3) Production of methyl 3-ethylenedioxy-5β-cholan-24-oate () 571.1g (1.47M) of methyl 3-oxo-5β-cholan-24-oate (), para-toluenesulfonic acid 1 Hydrate 6.5g, 2-ethyl-1
-Methyl-1,3-dioxolane 1536g
(13.2M) was placed in a 5-volume, 4-necked flask and heated to reflux for 2.5 hours while stirring. After standing overnight, the precipitated white crystals were collected, washed with cold methanol, heated to 100°C for 2 hours, then heated to 120°C.
It was dried for 3 hours. 474.4g; mp159-61℃. An additional 73.4 g of the desired product was obtained from the mother liquor and washing liquid. Target yield: 547.8g (yield 86.6%) IR spectrum ( _νnudjolnax ): 1740cm ^-1 NMR spectrum (CDCl ₃ , δppm): 3.60
(3H, S, -CO ₂ CH ₃ ), 3.87 (4H, S,

[Formula]) (4) 3-ethylenedioxy-5β-cholane-24-
Preparation of All () 4.3 g (0.1125 M) of lithium aluminum hydride in 500 ml of dry tetrahydrofuran is
methyl 3-ethylenedioxy-5β-cholan-24-oate () in 300 ml of dry tetrahydrofuran.
62.8g (0.145M) of solution was heated at an internal temperature of 10-20℃ for 10 minutes.
It was added dropwise once for a minute and then stirred at room temperature for 4 hours. After standing overnight, the reaction mixture was refluxed for 2 hours, and thin layer chromatography showed that the starting material still remained, so 1.42 g (0.0375 M) of lithium aluminum hydride was added.
was added, and the mixture was further stirred at room temperature for 2 hours. As a result, the raw material completely disappeared (confirmed by thin layer chromatography). 30ml of water to the reaction mixture
was added to decompose excess lithium aluminum hydride, filtered through Celite, the solvent was distilled off from the solution, 500 ml of benzene was added to the remaining white slurry, and after drying over magnesium sulfate, the solvent was distilled off. . The resulting viscous oil contains n-
300 ml of hexane was added and the solvent was distilled off to obtain 58.9 g of a white solid (yield: 100%). mp131−2℃
(n-hexane). IR spectrum ( _νnujiornax ): 3550, 1100
cm ^-1 NMR spectrum (CDCl ₃ , δppm): 0.63
(3H, S, 18−CH ₃ ), 0.94 (3H, S, 19−
_CH3 ), 1.87 (1H, S, 24-OH, _D2O elimination),
3.57 (2H, t, J=7H ₂ 24−H), and 3.89
(4H, S,

[Formula]) (5) 3-ethylenedioxy-5β-cholane-24-
Preparation of R () 58.6 g (0.272 M) of pyridinium chlorochromate in 55 ml of chloroform and 22.3 g (0.272 M) of anhydrous sodium acetate are placed in a 1 volume 4-neck flat-bottomed Colpen, and 3-ethylenedioxy- 5β-cholan-24-
A solution of 55.7 g (0.136 M) of All () was added in one portion at room temperature under stirring. The reaction mixture was heated at room temperature for 2
After stirring for an hour, 14.4 g (0.067 M) of pyridinium chlorochromate and 5.6 g (0.068 M) of anhydrous sodium acetate were added, and the mixture was further stirred for 30 minutes. 500 ml of ether was added to the reaction mixture, the ether layer was decanted, the resinous residue collected at the bottom was washed with ether (500 ml x 3), the ether layers were combined, and the solvent was distilled off. The remaining dark brown viscous oil was dissolved in 50 ml of benzene and applied to a column of 700 g of silica gel (60-80 mesh).
Elution was performed with a benzene-ethyl acetate mixture (49:1). Eluate 5 after elution 2.5 was taken and the solvent was distilled off to obtain 39.0 g of white crystals (yield 70.6%). mp141-2°C (n-hexane). IR spectrum ( _νnujiolnax ): 2710,
1720, 1095 cm ^-1 NMR spectrum (CDCl ₃ , δppm): 0.64
(3H, S, 18−CH ₃ ), 0.92 (3H, S, 19−
CH ₃ ), 3.86 (4H, S,

[Formula]), 9.64 (1H, t, CH ₂ -CHO) MS: m/e 402 (M ⁺ ) Elemental analysis value: C ₂₆ H ₄₂ O ₃ (as molecular weight 402.60) Calculated value: C 77.56% H 10.52% Measured values: C 77.55% H 10.52% (6) 3-ethylenedioxy-5β-cholesto-24
Preparation of -ene () (i) Preparation of triphenyl phosphine isopropylidene reagent 100 ml of dry ether and isopropyl
Triphenyl phosphonium bromide
7.8 g (0.02 M) was added to a 500 ml pressure flask under an argon atmosphere, and 7.8 g (0.02 M) of 15
% n-butyllithium solution was added via syringe, capped tightly and shaken for 16.5 hours to obtain a deep red solution containing the title reagent. (ii) 3-ethylenedioxy-5β-cholesto-
Preparation of 24-ene To the reagent solution obtained in (i), 3-ethylenedioxy-5β-cholan-24- dissolved in 150 ml of dry ether under stirring in a stream of argon was added.
A solution of 5.1 g (0.0127 M) of Earl () was added, the mixture was tightly stoppered, and the mixture was shaken for 3 hours. When 150 ml of primary ether was added to the resulting red reaction solution to decompose unreacted reagents, the red color disappeared.
A white precipitate formed. After filtering, the precipitate on the paper was washed with 50 ml of ether, the liquid and washing liquid were combined and filtered again, and the solvent was distilled off to obtain 6.5 g of a white viscous oily residue. This was chromatographed on a 100 g column of silica gel (Wako Gel C-200), fractionated with a benzene-ethyl acetate mixture (99:1), and after 200 ml of elution,
400 ml was taken and the solvent was distilled off to obtain 5.1 g of white viscous oily product (yield 93.9%). This product crystallizes when left at room temperature and becomes white flaky crystals when recrystallized from methanol. mp64-6℃ (from methanol) IR spectrum ( _νnudyolnax ): 1095cm ^-1 MS: m/e428 (M ⁺ ), 413 (M ⁺ -15) NMR spectrum (CDCl ₃ , δppm): 0.66
(3H, S, 18−CH ₃ ), 0.95 (3H, S, 19−
_CH3 ), 1.59 and 1.65 (3H, S, 26, respectively
27−CH ₃ ), 3.90 (4H, S,

[Formula]), 5.05 (bm, 1H, 24-H) Elemental analysis value: C ₂₉ H ₄₈ O ₂ (assuming molecular weight 428.67) Calculated value: C 81.25% H 11.29% Measured value: C 80.91% H 11.23% (7 ) 3-ethylenedioxy-24・25-epoxy-
Preparation of 5β-cholestane () 10 g of 3-ethylenedioxy-5β-cholest-24-ene () in 80 ml of dichloromethane
(0.024 M) and 5.7 g of sodium bicarbonate in 80 ml of dichloromethane at -2 to -5°C under stirring.
A solution of (0.028M) was added dropwise over 30 minutes, and stirring was continued for 1 hour at the same temperature.The reaction mixture was then returned to room temperature and further stirred for 2 hours. The resulting reaction solution was a 10% aqueous sodium sulfite solution (100
After washing with saturated saline (100 ml x 2) and distilling off the solvent, a pale yellow viscous oil product was obtained.
10.7g was obtained. This product was chromatographed on a 500 g column of silica gel (60-80 mesh) along with 10.7 g of the product obtained by repeating the same procedure once more. benzene 3.2
Elute with benzene-ethyl acetate (39:
1), the 3.2 fraction after the 0.4 elution was taken, and the solvent was distilled off to obtain a pale yellow candy-like product, which solidified after being left overnight. 19.6g
(Yield 92.7%). mp: 68-70℃ IR spectrum ( _νnudjolnax ): 1465, 1100
cm ^-1 NMR spectrum (CDCl ₃ , δppm): 0.68
(3H, S, 18−CH ₃ ), 0.97 (3H, S, 19−
_CH3 ), 1.26 (6H, S, 26, 27- _CH3 ), 2.65
(1H, t, J = 5H ₂ , 24-H), 3.91 (4H, S,

[Formula]) (8) Production of 24ξ・25-dihydroxy-5β-cholestan-3-one () 3-ethylenedioxy-24・25-epoxy-
5β-cholestane () 10.3g, 2N sulfuric acid 300ml
and 400 ml of tetrahydrofuran was stirred at room temperature for 3.5 hours. Then, the reaction mixture was diluted with isopropyl ether (300ml x 1, 200ml
x 2), combine the extracts, add saturated sodium bicarbonate solution (300ml x 3) and then saturated saline solution (200ml x 2).
After drying with anhydrous magnesium sulfate and filtering, the solvent was distilled off and the residue was purified with n-
After washing with hexane, 8.5 g of white crystals (yield
87.6%). mp: 140-142℃ Elemental analysis value: C ₂₇ H ₄₆ O ₃ (as molecular weight 418.64) Calculated value: C 77.46% H 11.08% Measured value: C 77.60% H 11.20% IR spectrum ( _νnudjolnax ): 3480, 1710
cm ^-1 NMR spectrum (CDCl ₃ , δppm): 0.66
(3H, S, 18−CH ₃ ), 0.98 (3H, S, 19−
_CH3 ), 1.13 and 1.18 (3H, S, 26, respectively)
27−CH ₃ ), 2.44 (2H, S, 24ξ, 25−OH, +
D ₂ O disappearance), 3.24 (1H, m, 24-H) (9) 24ξ-acetoxy-25-hydroxy-5β-
Production of cholestan-3-one (X) A solution consisting of 15.5 g of 24ξ·25-dihydroxy-5β-cholestan-3-one (), 175 ml of acetic anhydride, and 500 ml of pyridine was stirred at room temperature for 16 hours. The disappearance of raw material spots was confirmed by thin layer chromatography. The resulting light orange reaction solution was poured into ice water 3.0, extracted with isopropyl ether (500ml x 3), the extracts were combined, and washed with 10% sulfuric acid (500ml x 2) and saturated sodium bicarbonate water (500ml x 2). The mixture was dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The resulting viscous oil was chromatographed on a column of silica gel (60-80 mesh; 400 g). Elute with benzene-ethyl acetate (9:1)
After 3.0 elution, take 11 portions, then elute with benzene-ethyl acetate (4:1) and remove the 4.
Take the fractions, combine both fractions, distill off the solvent,
A colorless and transparent viscous oily product was obtained. This product partially solidified upon standing at room temperature. 15.7g (yield
92.0%). IR spectrum (ν film _nax ): 3470, 1730,
1710cm ^-1 NMR spectrum (CDCl ₃ , δppm): 0.70
(3H, S, 18−CH ₃ ), 1.05 (3H, S, 19−
CH ₃ ), 1.22 (6H, S, 26・27−CH ₃ ), 2.09
(3H, S, 24−OCOCH ₃ ), 2.27 (1H, S, 25−
OH, ⁺ D ₂ O), 4.73 (1H, m, 24H) (10) Production of 24ξ・25-diacetoxy-5β-cholestan-3-one (XI) 24ξ-acetoxy-25-hydroxy-5β-
Mix 14.65 g of cholestan-3-one (), 160 ml of acetic anhydride and 12 ml of anhydrous pyridine and
The mixture was heated to reflux for an hour. After cooling the resulting pale brown transparent solution to room temperature, it was poured into 1.5 liters of ice water and extracted with ethyl acetate (300 ml x 1 and 200 ml x 2).
Combine the extracts and add 2N H ₂ SO ₄ (200ml x 2), saturated sodium bicarbonate solution (200ml x 4) and saturated saline (300ml).
×2), dried over anhydrous magnesium sulfate, and then distilled off the solvent to leave a viscous oily residue.
16.1g was obtained. Add this entire amount to silica gel (60−80
Chromatography was carried out on a column of 250 g of mesh. n-hexane-ethyl acetate (9:1)
Divided into fractions of 200 ml each, fractions 7 to 29 were combined (4.6), the solvent was distilled off, and 10.9 g (yield 68.2%) of product (XI) was obtained as a colorless and transparent viscous product. Obtained as an oil. IR spectrum (ν neat _nax ): 1730, 1710 cm ^-1 MS: m/e502 (M ⁺ ), 442 (M ⁺ -60), 382
(M ⁺ −120) NMR spectrum (CDCl ₃ , δppm): 0.67
(3H, S, 18−CH ₃ ), 1.00 (3H, S, 19−
CH ₃ ), 1.41 and 1.45 (3H, S, 26.
27- _CH3 ), 1.93 (3H, S, 25- _OCOCH3 ), 2.05
(3H, S, 24−OCOCH ₃ ) and 5.07 (1H, m,
24-H). (11) 24ξ・25−Diacetoxycholester 1・4−
Production of dien-3-one (XII) 9.3g (18.5mM) of 24ξ・25-diacetoxy-5β-cholestan-3-one (XI), 12.60g (55.5mM) of dichlorodicyanobenzoquinone and 170ml of dioxane were mixed into 500ml volumes of 4 bottles. The mixture was placed in a flask and refluxed for 5.5 hours while stirring on an oil bath. After confirming the disappearance of the raw material (XI) by thin layer chromatography, pale yellow precipitated crystals were removed from the reddish-brown reaction solution, and the solvent was distilled off from the reddish-brown liquid. 16 g of the obtained reddish brown viscous oily residue was mixed with 50 g of silica gel, and this was mixed with silica gel (60-80
400 g) of n-hexane-ethyl acetate (9:1).
Then, change the elution to n-hexane-ethyl acetate (3:1) and fractionate into 500 ml portions. Fractions Nos. 5 to 14 were combined and the solvent was distilled off to leave a red viscous oily residue of 8.5 ml. I got g. This substance shows a spot at the origin in thin layer chromatography and has a wavelength of 2250nm in the infrared absorption spectrum.
Since it was found that it was contaminated with dichlorodicyanobenzoquinone because it had an absorption of -CN, it was further purified using an alumina column. That is, the above red viscous oily residue was dissolved in benzene, put into a column (2.5 x 23.5 cm) containing 85 g of neutral alumina (Woelm neutral), eluted with benzene-ethyl acetate (9:1), and poured into 12 ml portions. It was collected as a fraction. The fractions No. 5 to 96 were combined and the solvent was distilled off to produce an orange viscous oily product (XII).
6.2g (yield 67.2%) was obtained. IR spectrum (ν neat _nax ): 1735, 1660,
1625, 1605 cm ^-1 UV spectrum (λ ^EtOH _nax , nm): 247, 301
(Weak) NMR spectrum (CDCl ₃ , δppm): 0.74
(3H, S, 18−CH ₃ ), 0.79 (1H, S), 1.22
(3H, S, 19−CH ₃ ), 1.43 and 1.47 (respectively
3H, S, 26・27−CH ₃ ), 1.95 (3H, S, 24−
OCOCH ₃ ), 2.07 (3H, S, 25−OCOCH ₃ ),
5.10 (1H, m, 24-H) 5.99 (1/3H, S),
6.06 (1H, S, 4-H), 6.21 (1H, dd, J=2
Hz, 10Hz, 2-H), 7.06 (1H, d, J=10Hz,
1-H) This product shows 1605 in IR spectrum.
Since the absorption at cm ^-1 is too strong compared to the absorption at 1625 cm ^-1 and there is a weak absorption at 301 nm in the UV spectrum, it was confirmed that it contains 24ξ・25-diacetoxytrienone (). and its amount is shown in the NMR spectrum.
A signal corresponding to one hydrogen atom (18-CH ₃ ) at 0.79ppm, and a hydrogen atom at 5.99ppm
Signal equivalent to 1/3 (4-H)
It is approximately 25% due to the presence of (12) 24ξ・25-Diacetoxycholester 1・4・
Production of 6-trien-3-one () Orange viscous oily product (XII) obtained in (12) above
6.1g (0.0122M), chloranil 15.0g
A mixture of 5.6 g (0.061 M), 2H-dichlorodicyanobenzoquinone (0.024 M) and 250 ml of sec-amyl alcohol was placed in a 1-volume 4-necked flat-bottomed flask and heated under stirring on an oil bath under reflux for 8.5 hours. The obtained dark brown reaction solution was cooled with ice, 6.9 g of precipitated golden crystals were removed, the dark brown liquid was concentrated, benzene was added to the residue, and the mixture was filtered.
It was separated into a liquid and pale brown crystals that had precipitated. The crystals (8.4 g) were washed with cold benzene, the washing liquid was combined with the above liquid, and the solvent was distilled off to obtain 10.8 g of a dark brown viscous oil. This product was dissolved in benzene and chromatographed on a 150 g column (2.5 x 35 cm) of alumina (neutral Woelm Alumina). The mixture was eluted with benzene-ethyl acetate (19:1) and fractionated into 10 ml fractions. Fractions Nos. 5 to 96 were combined and the solvent was distilled off to obtain 4.3 g of a reddish-orange residue. This product was further chromatographed using a 100 g column (3.5 x 25 cm) of silica gel [Wako Gel C-200]. Elute with benzene-ethyl acetate (9:1) and fractionate into 10 ml fractions. Fractions Nos. 46 to 150 were combined and the solvent was distilled off.
3.25 g of an orange viscous oil product () was obtained. Fractions No. 32 to 42 still contained impurities, so chromatography was performed again on a 50 g column of silica gel [Wako Gel C-200], eluted with benzene-ethyl acetate (9:1), and 10 ml each was added. Fractions Nos. 16 to 35 were combined and the solvent was distilled off to produce an orange viscous oil ()0.5
g was further obtained. Yield of product () = 3.75g (yield 61.7
%). IR spectrum (ν film _nax ): 1740, 1655,
1605, 1585cm ^-1 UV spectrum ( _λethanolnax ): 224nm (ε
= 10200) 256nm (ε=8800) 301nm (ε=
11000) MS: m/e496 (M ⁺ ), 436 (M ⁺ -60), 394,
376 NMR spectrum ( _CDCl3 , δppm): 0.79
(3H, S, 18−CH ₃ ), 1.19 (3H, S, 19−
CH ₃ ), 1.43 and 1.47 (3H, S, 26.
27−CH ₃ ), 1.95 (3H, S, 24−OCOCH ₃ ), 2.07
(3H, S, 25−OCOCH ₃ ), 5.10 (1H, m, 24−
H), 6.29-6.00 (4H, m, 2, 4, 6, 7-
H), 7.07 (1H, d, J=10Hz, 1-H). (13) 24ξ・25-dihydroxycholester 1・
Preparation of 4,6-trien-3-one () 24ξ·25-diacetoxycholester 1,4,6-triene () in 6 ml of methanol
1.5 ml of 12% hydrous methanolic potassium hydroxide was added to 0.158 g of the solution under ice cooling, and the mixture was stirred for 2.5 hours. Next, 30 ml of ethyl acetate and 5 ml of water were added to the reaction solution, the ethyl acetate layer was separated, and the aqueous layer was further extracted with ethyl acetate (100 ml x 2).
The ethyl acetate layer was combined with the previous ethyl acetate layer, dried over magnesium sulfate, filtered, and the solvent was distilled off to obtain 0.142 g of a residue, which was recrystallized from acetonitrile to yield 0.0895 g of the desired product () (yield 68.2).
%) was obtained as pale yellow crystals. mp: 205-7℃ IR spectrum ( _νnudjolnax ): 1650,
1600, 1580cm ^-1 UV spectrum ( _λethanolnax ): 224nm (ε
= 11600) 257nm (ε=9800) 301nm (ε=
12700) MS (m/c): 412 (M ⁺ ), 394 (M ⁺ -18) NMR spectrum (CDCl ₃ , δppm): 0.80
(3H, S, 18−CH ₃ ), 1.17 (3H, S, 19−
CH ₃ ), 1.20 and 1.22 (3H, S, 26.
27−CH ₃ ), 2.16 (2H, S, 24・25−OH) (D ₂ O
erasure), 3.30 (1H, m, 24-H), 5.99-6.28
(4H, m, 2/4/6/7-H), 7.06 (1H,
d, J=10MZ, 1-H) Elemental analysis value: C ₂₇ H ₄₀ O ₃ (as molecular weight 412.59) Calculated value: C 78.59% H 9.77% Measured value: C 78.22% H 9.51%

Claims (1)

[Claims] Linear formula () The following formula () was obtained by treating lithocholic acid with a lower alkanol in the presence of a dehydrating agent. The lower alkyl 3α-hydroxy-5β-cholan-24-oate of was oxidized with Johns reagent to obtain the following formula () lower alkyl 3-oxo-5β-cholane-24-
Oate was reacted with 2-methyl-2-ethyl-1,3-dioxolane to obtain the following formula () Lower alkyl 3-ethylenedioxy-5β-cholan-24-oate was reduced with lithium aluminum hydride to obtain the following formula () oxidizing 3-ethylenedioxy-5β-cholan-24-ol with pyridinium chlorochromate,
The following formula obtained () The following formula () was obtained by treating 3-ethylenedioxy-5β-cholan-24-al with triphenylphosphine isopropylidene reagent. 3-ethylenedioxy-5β-cholesto-24-
The following formula () obtained by oxidizing ene with an organic peracid 3-ethylenedioxy-24ξ・25-epoxy-
When acid is applied to 5β-cholestane, the following formula () is obtained: 24ξ・25-dihydroxy-5β-cholestane-
The following formula (X) is obtained by treating 3-one with an acylating agent at room temperature. 24ξ-acyloxy-25-hydroxy-5β-
The following formula (XI) was obtained by treating cholestan-3-one with an acylating agent under heating. The following formula (XII) was obtained by oxidizing 24ξ・25-diacyloxy-5β-cholestan-3-one with 2,3-dichloro-5,6-dicyanobenzoquinone. 24ξ・25-diacyloxycholester-1・4-
Dien-3-one to 1,4-dihydro-2,3-
Dehydrogenation with chloranil in the presence of dichloro-5,6-dicyanobenzoquinone gave the following formula () 24ξ・25-diacetoxycholester 1, 4, 6
- The following formula (), characterized by alkaline hydrolysis of trien-3-one 24ξ・25-dihydroxycholester 1, 4, 6
-Production method of trien-3-one.