DK158991B - CHOLE STAGE DERIVATIVES THAT MAY BE USED AS INTERMEDIATES FOR USE IN THE PREPARATION OF HOMOVITAMIN-D3 DERIVATIVES - Google Patents

Description

in DK 158991B

The present invention relates to novel cholestain derivatives which can be used as intermediates for use in the preparation of hydroxylated 24-homovitamin derivatives.

The cholestead derivatives of the invention are characterized in that they have the formula set forth in the characterizing part of the claim. The compounds are designated (22E) -la, 30-di (acyl or benzoyl) -25-hydroxy-24-homocholesta-5,22-dienes.

10 It is well known that vitamin-D regulates calcium and phosphorus metabolism in animals and humans, and it is now clearly established that the biological effect of vitamin-D depends on the metabolic conversion of the vitamin in vivo to hydroxylated derivatives. Thus, vitamin D, "in vivo, is hydroxylated to 25-hydroxy vitamin-D 2 in the liver, which is converted into 1", 25-dihydroxyvitamin-D3 in the kidneys. It is the latter compound that is recognized to be the circulating hormonal form of Vitamin D.

Due to the biological ability of the compounds to promote calcium and phosphorus transport in the intestine and to mobilize and mineralize bones, these forms of vitamin D are important pharmaceutical compounds that are particularly suitable

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to be used in the treatment of various bone disorders.

Vitamin derivatives and their preparation and their use are discussed in a variety of patent publications and in other literature. Eg. U.S. Pat.

3,556,924 25-hydroxy cholecalciferol; U.S. Pat.

3,697,559 discloses 1,25-dihydroxycholecalciferol; US

U.S. Patent No. 3,471,996 discloses 1α-hydroxychole-calciferol; U.S. Patent No. 3,786,062 discloses 22-35 dehydro-25-hydroxycholecalciferol; U.S. Pat.

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2,880,894 discloses 1,25-dihydroxyergocalciferol; U.S. Patent No. 4,201,881 discloses 24,24-difluoro-1α, 25-dihydroxycholecalciferol; U.S. Patent No. 4,196,133 discloses 24,24-difluoro-1α, 25-dihydroxycholecalciferol.

5

Said derivatives of 24-homo-vitamin-Dg have been found to exert excellent vitamin-D-like effect, and for that reason they can be readily used in place of vitamin-Dg or derivatives thereof for known purposes such as e.g. for the treatment of various morbid conditions which appear in calcium and phosphorous imbalances such as hypopa-rathyroidism, osteodystrophy, osteomalacia and osteopo-rose.

In addition, these derivatives exhibit an unexpectedly high antineoplastic effect relative to 1α-hydroxyvitamin Dg and 1α, 25-dihydroxyvitamin Dg, and this effect is unexpectedly and surprisingly exhibited with no increased calcemic effect.

These properties make the homo compounds particularly suitable as substitutes for Ια-hydroxyvitamin Dg and 1α, 25-dihydroxyvitamin Dg suggested for the treatment of leukemic diseases.

These derivatives are 24-homovitamins and especially le, 25-di-hydroxy-22E (or Z) -dehydro-24-homovitamin-Dg and 1a, 25-dihydroxy-24-homovitamin-Dg.

Said homovitamin compounds can be prepared as indicated in the following reaction scheme and as described below. In the schematic and detailed description of the process, the same numbers identify the same compounds.

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DK 158991 B

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'' 'Y' ^ o th? cko * on \ f ^ j ^) Ί _

~ 2. R = jHP

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Ori r ^ ·. Loh · - f-fS ^ jX „

JfYY & P- * ΛΦ ~ 2

κΛ R * -H

- ~ jo_ hc - CC0H homw il rr

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4

The preparation of the homovitamin Dg derivatives is further described below:

Bisnorcholenoic acid acetate (a) was reduced with lithium aluminum hydride and then oxidized with dichlorodicyanobenzoquinone to 1,4,6-trien-3-one (b) in 47% yield. The 22-THP ether of (b) was treated with alkaline hydrogen peroxide to give the 1α, 2α epoxide (1) in a 41% yield. Reduction of (1) with lithium and ammonium chloride in 10 liquid ammonia tetrahydrofuran at -78 ° C and subsequent treatment with chloromethyl methyl ether gave the dimethoxymethyl ether (2) in a 38% yield. Removal of the THP group followed by Swern oxidation gave the aldehyde (4) in a yield of 81%. This was reacted with vinyl magnesium bromide to give the allyl alcohol (5) in a 94% yield. The alcohol was heated at reflux in xylene with triethyl orthoacetate and a catalytic amount of propionic acid to give the ester (6) in a 93% yield. Then the ester (6) was reacted with methyl magnesium bromide 20 to give the alcohol (7) in a yield of 93%. Removal of the MOM group followed by acetylation afforded (22E) -1α, 30-diacetoxy-25-hydroxy-24-homo-cholesta-5,22-diene (9) in 73% yield.

Allyl bromination of (9) with N-bromosuccinimide followed by treatment with tetra-n-butylammonium bromide and then with tetra-n-butylammonium fluoride gave the 5,7,22-triene (10) as a major product in a 24% yield. The 5,7,22-triene (10) was irradiated with an intermediate-pressure mercury lamp in benzene-ethanol for 5 minutes, then heated at reflux and hydrolyzed to give (22E) -la, 25-dihydroxy-22-dehydro-benzene. 24-homovitamin-Dg (11) in a yield of 22%.

The 5,22-diene (9) was selectively hydrogenated to give the 5-ene (12) in a 92% yield. This compound was converted to 1α, 25-dihydroxy-24-homovitamin-D3 (14) via 5.7

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5 diene (13) as described above in a total yield of 12%.

In the following description of the preparation of the 5-end 24-homo-vitamin Dg compounds, the melting points were determined by hot-stage microscope and indicated uncorrected. The 1 HNMR spectra were recorded with a Hitachi R-24A (60 MHz) NMR spectrometer in CDCl 3 with Me 2 Si as the internal standard, unless otherwise indicated. Mass spectra were recorded with a Shimadzu QP-1000 mass spectrometer at 70 eV. UV spectra were obtained in ethanolic solution with a Shimadzu UV-200 dual-beam spectrophotometer. Column chromatography was performed using silica gel (E.

Merck, silica gel 60, 70-230 mesh). Preparative thin-layer chromatography was performed on pre-coated silica gel plates (E. Merck, silica gel 60 F254 mm thick).

The usual work up is done by dilution with water, extraction with an organic solvent indicated in brackets, washing the extract for neutral reaction, drying over anhydrous magnesium sulfate, filtration and removal of the solvent under reduced pressure. The following abbreviations are used: THP - tetrahydropyranyl; THF - tetrahydrofuran; ether - diethyl ether, MeOH-methanol, MOM - methoxymethyl. Temperatures are given in 25 ° C.

22-Hydroxy-23,24-dinorchola-1,4,6-trien-3-one (b)

To a solution of 30-acetoxydinorcholenic acid (a) (7.0 g, 18.04 mmol) in THF (20 ml) was added lithium aluminum hydride (3.0 g, 78.95 mmol). The mixture was stirred at 60 ° C for 14 hours. To the reaction mixture was gently added water and ethyl acetate. Filtration and removal of the solvent gave a residue (5.2 g). This was treated in dioxane (140 35 ml) with dichlorodicyanobenzoquinone (11.7 g, 51.54 mmol) under reflux for 14 hours. After cooling to room temperature, the reaction mixture was filtered and the filtrate

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6

Evaporated to a residue applied to a column of alumina (200 g). Elution with dichloromethane gave the triene (b) (2.8 g 47%) m.p. 156-157 ° C (ether) υνλ EtOH max max j yyyy (epSion): 299 (13000), 252 (9200), 224 (12000), 1 H NMR (CDCl 3) δ: 0.80 (3H, s, 18 -Hg), 1.04 (3H, d, J = 6 Hz, 21-H3), 1.21 (3H, s, 19-H3), 3.10-3.80 (3H, m, 22-H2 and OH), 5.90-6.40 (4H, m, 2-H, 4-H, 6-H and 7-H), 7.05 (1H, d, J = 10 Hz, 1-H), MS m / z: 326 (M ~), 311, 308, 293, 267, 112.

1 ', 2α-Epoxy-22-tetrahydropyranyloxy-23,24-dinorchola-4,6-dien-3-one (1)

The alcohol (b) (2.7 g, 8.28 mmol) in dichloromethane (50 ml) was treated with dihydropyran (1.5 ml, 16.42 mmol) and p-toluenesulfonic acid (50 mg) at room temperature for 1 hour. Ordinary work-up (ethyl acetate for the extraction) gave a crude compound. To a solution of this compound in MeOH (70 ml) was added 30% H 2 O 2 (4.8 ml) and 10% NaOH / MeOH (0.74 ml) and the mixture was stirred for 14 hours at room temperature. Usual work-up (ethyl acetate for the extraction) gave a crude compound which was applied to a column of silica gel (50 g). Elution with benzene-ethyl acetate (100: 1) gave the epoxide (1) (1.45 g, 41%): m.p. 113-25 115 ° C (hexane) UV / EtOH / max nm (epsilon): 290 (22000), 1 H NMR (CDCl 3) δ: 0.80 (3H, s, 18-Hg), 1.04 (3H , d, J = 6 Hz, 21-Hg), 1.21 (3H, s, 19-H3), 3.38 (1H, dd, J = 4 and 1.5 Hz, 1-H), 3.55 ( 1H, d, J = 4 Hz, 2-H), 3.30-4.10

(4H, m, 22-H2 and THP), 4.50 (1H, m, THP), 5.58 (1H, d, J

30 = 1.5 Hz, 4-H), 6.02 (2H, s, 6-H and 7-H), MS m / z: 342 (M + - DHP), 324 (M + - Η0ΤΗΡ), 309, 283, 85.

1α, 3β-dimethoxy-23,24-dinorchol-5-ene-22-tetrahydropyranyl ether (2)

Lithium (5.00 g) was added in small portions to liquid ammonia (200 ml) at -78 ° C in an argon atmosphere over 35 minutes.

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7 30 minutes. After stirring for 1 hour at -78 ° C, 1α, 2α-epoxy-22-tetrahydropyranyloxy-23,24-dinoro-chola-4,6-dien-3-one (1) is added dropwise (2.00 g, 4). , 69 mmol) in dry THF (50 ml) at -78 ° C over 30 minutes, and the mixture was stirred for 1 hour at -78 ° C. To the reaction mixture was added anhydrous NH 2 Cl (60 g) in small portions over 1 hour at -78 ° C. After 1.5 hours, the cooling bath was removed and most of the ammonia was removed by genre bubbling with argon. Usual work-up (ether was used as solvent) gave an impure compound. This was treated with chloromethyl methyl ether (2.0 mL, 26.34 mmol) and N, N-diethylcyclohexylamine (4.6 mL, 24.93 mmol) in dioxane (20 mL) at 45 ° C for 24 hours. Usual work-up (ethyl acetate) gave an impure compound which was applied to a column of silica gel (40 g). Elution with hexane-ethyl acetate (5: 1) gave the dimethoxymethyl ether (2) (922 mg, 38%) as an oil. 1 H NMR δ: 0.70 (3H, s, 18-Hg), 1.02 (3H, s, 19-H3), 1.04 (3H, d, J = 6 Hz, 21-Hg), 3 , 34 (3H, 20 s, -0-CH 3), 3.37 (3H, s, -0-CH 3), 4.63 (2H, ABq, J = 7

Hz, 6 AB = 11 Hz, Ia-O-CH2-0-), 4.64 (2H, S, 30-0-CH2-0-) and 5.50 (1H, m, 6-H).

Ig, 3fl-dimethoxy-23,24-dinorchol-5-en-22-ol (3) The THP-ether (2) (922 mg, 177 mmol) in THF (8 ml) and MeOH (8 ml) were treated with 2 M HCl (1 ml) for 2 hours at room temperature. Usual work-up (ethyl acetate) gave an impure compound which was applied to a column of silica gel 30 (40 g). Elution with hexane-ethyl acetate (2: 1) gave the alcohol (3) (678 mg, 88%) as an amorphous solid. 1 H NMR δ: 0.70 (3H, s, 18-H3), 1.02 (3H, s, 19-Hg), 1.04 (3H, d, J = 6 Hz, 21-H3), δ , 34 (3H, s, -0-CHg), 3.38 (3H, s, -0-CHg), 4.65 (2H, ABq, J = 7 Hz, δ AB = 11 Hz, Ia-0- CH2-0-), 4.66 (2H, s, 30-0-CH2-0-), 5.53 (1H, m, 6-H).

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8 µg, 30-dimethoxy-23,24-dinorchol-5-en-22-al (4)

To a solution of oxalyl chloride (0.27 mL, 3.09 mmol) in dichloromethane (8 mL) was added at -78 ° C under argon dimethyl sulfoxide (0.44 mL, 6.21 mmol). The mixture was stirred for 10 minutes at -78 ° C. To the solution was added the alcohol (3) (660 mg, 1.51 mmol) in dichloromethane (5 ml) at -78 ° C.

After stirring for 15 minutes, triethylamine (1.89 mL, 13.6 mmol) was added. The mixture was stirred at -78 ° C under argon 10 for 5 minutes and warmed to room temperature. Usual work-up (ether) yielded an impure compound applied to a column of silica gel (30 g). Elution with hexane-ethyl acetate (4: 1) gave the aldehyde (4) (607 mg, 92%) as a crystalline mass, mp 71-72 ° C (hexane), *H-NMR δ: 0.74 (3H, s, 18-H3), 1.04 (3H, s, 19-Hg), 1.12 (3H, d, J = 6 Hz, 21-H3), 3.35 (3H, s, -O-CH ), 3.39 (3H, s, -O-CH 3), 3.7 (1H, m, 10-H), 4.65 (2H, ABq, J = 7 Hz, δ AB = 11 Hz, 1a - O-CH 2 -O-) 4.66 (2H, s, 30-O-CH-O-), 5.52 (1H, m, 6-H) and 9.61 (1H, d, J = 3 Hz, -CHO), analysis calculated for C26H4205: C, 71.85; H, 9.74. Found: C, 71.71; H, 9.68.

1a, 30-dimethoxychola-5.23 dien-22-ol (5)

To magnesium (70 mg, 2.92 mmol) in THF (3 ml) was added a 50% solution of vinyl bromide in THF (0.42 ml, 2.98 mmol).

The mixture was stirred under argon at room temperature for 30 minutes. To the prepared Grignard reagent, the aldehyde (4) (5.95 mg, 1.37 mmol) in THF (6 ml) was added at room temperature. The mixture was stirred for 1 hour at room temperature.

Ordinary reprocessing (ether) afforded an impure compound applied to a column of silica gel (30 g). Elution with hexane-ethyl acetate (3: 1) gave the allyl alcohol (5) (595 mg, 94%) as an amorphous solid. 1 H-NMR δ: 0.70 (3H, s, 18-H3), 1.02 (3H, s, m 19-H3), 3.35 (3H, s, -O-CH 3), 3.38 (3H,

S, -0-CH 3), 3.69 (1H, m, 10-H), 4.20 (1H, m, 22-H), 4.64 (2H, ABq, J = 7 Hz, δ AB = 11 Hz, 1a-O-CH 2 -O-), 4.65 (2H, s, 30-O-CH 2 -O-), 5.52 (1H, m, 6-H), 4.90-6 , 0 (3H, m, 23-H)

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9 and 24-H2).

(22E) -lg, 3fl-dimethoxymethoxy-27-norcholesta-5,22-diene-26-oanoic acid ethyl ester (6)

A solution of the allyl alcohol (5) (590 mg, 1.28 mmol), triethyl orthoacetate (1.0 ml, 5.64 mmol), propionic acid (4 drops) and xylene (8 ml) was heated under argon for 2 hours at reflux. Removal of the solvent under reduced pressure gave a residue applied to a column of silica gel (30 g). Elution with hexane / ethyl acetate (4: 1) gave in the ester (6) (630 mg, 93%) as an oil. H-NMR δ: 0.68 (3H, s, 18-H3), 0.97 (3H, d, J = 6 Hz, 21-Hg), 1.03 (3H, s, 19-H3), 1.24 (3H, t, J = 7 Hz, -CO 2 CH 2 CH 3), 3.35 (3H, s, -0-15 CH 3), 3.39 (3H, s, -O-CH 3), 3.70 ( 1H, m, 10-H), 4.11 (2H, g, J = 7 Hz, -CO 2 CH 2 CH 3), 4.64 (2H, ABq, J - 7 Hz, Delta AB = 11 Hz, l -CH 2 -O-), 4.65 (2H, s, 30-O-CH 2 -O-), 5.29 (2H, m, 22-H and 23-H), 5.52 (1H, m, 6-H).

Optionally, the 22E stereoisomeric compound (6) can be readily converted to the 22Z stereomer by processing oblique iodine. Thus, treatment of the compound (6) in ether with a catalytic amount of iodine (2%) relative to the compound (6) causes, under diffuse daylight, for 1 hour a trans to cis isomerization which after HPLC purification (Zorbax-Sil column, 4.6 x 25 cm, 6% 2-propanol / hexane) gives the 22Z stereoisomer.

(22E) - 1α, 3β - Dimethoxymethoxy-24-homocholesta-5,22-diene-25-30 ol (7)

To a solution of the ester (6) (605 mg, 1.14 mmol) in THF (6 ml) was added a 1 M solution of methyl magnesium bromide in THF (4.5 ml, 4.5 mmol) at room temperature. The mixture was stirred for 1 hour at room temperature. Usual work-up (ether) yielded an impure compound applied to a column of silica gel (30 g). Elution with hexane / ethyl acetate (3: 1)

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10 in gave the alcohol (7) (548 mg, 93%) as an oil. H-NMR δ in 0.68 (3H, s, 18-H3), 0.97 (3H, d, J = 6 Hz, 21-H3), 1.01 (3H, s, 19-Hg), 1 , 21 (6H, s, 26-H3 and 27-H3), 3.33 (3H, s, -0-CH3), 3.38 (3H, s, -0-CH3), 3.70 (1H, m, 10-H), 4.64 (2H, ABq, J - 7 Hz, 6 AB - 11 Hz, Ia-O-CH 2 -O-), 4.65 (2H, s, 35-O-CH 2 -0-), 5.29 (2H, m, 22-H and 23-H) and 5.50 (1H, m, 6-H).

(22E) -24-homocholesta-5,22-diene-1α, 3β, 25-triol (8)

A solution of the dimethoxymethyl ether (7) (540 mg, 1.04 mmol) in THF (15 ml) was treated with 6 M HCl (3 ml) at 50 ° C for 2.5 hours. Usual work-up (ethyl acetate) gave an impure compound which was applied to a column of silica gel 15 (20 g). Elution with hexane / ethyl acetate (1: 1) gave the triol (8) (428 mg, 95%) as a crystalline product. Mp. 164-166 ° C (hexane / ethyl acetate) 1 H-NMR δ: 0.68 (3H, s, 18-H3), 0.95 (3H, s, J = 6 Hz, 21-H3), 1.00 (3H, s, 19-H3), 1.20 (6H, s, 26-¾ and 27-¾), 3.80 (1H, m, 10-H), 3.92 (1H, m, 20 3a) -H), 5.30 (2H, 22-H and 23-H) and 5.53 (1H, m, 6-H).

(22E) -la, 3g-diacetoxy-25-hydroxy-24-homocholesta-5,22-diene (9) (a compound) 25 A solution of the triol (8) (395 mg, 0.919 mmol) in pyridine (2 ml) was treated with acetic anhydride (1 ml) at room temperature for 16 hours. Usual work-up (ethyl acetate) gave an impure compound applied to a column of silica gel (20 g). Elution with hexane / ethyl acetate (2: 1) gave the diacetate (9) (361 mg, 77%) as an oil. 1 H NMR δ: 0.67 (3H, s, 18-H3), 0.97 (3H, d, J = 6 Hz, 21-¾), 1.07 (3H, s, 19-¾), 1 , 21 (6H, s, 26-¾ and 27-¾), 2.01 (3H, s, acetyl), 2.04 (3H, s, acetyl), 4.98 (1H, m, 3a-H) , 5.05 (1H, m, 11f-H), 5.31 (2H, m, 22-H and 23-H), and 5.52 (1H, m, 6-H).

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11 (22E) -le, 3β-diacetoxy-25-hydroxy-24-homocholesta-5,7,22-triene (10)

A solution of 5-ene (9) (51 mg, 0.0992 mmol) and N-bromo-5-succinimide (21 mg, 0.118 mmol) was heated under reflux under argon for 20 minutes in carbon tetrachloride (3 ml). After the mixture was cooled to 0 ° C, the precipitated precipitate was filtered off. The filtrate was concentrated below 40 ° C to give a residue. This was treated 10 in THF (5 ml) with a catalytic amount of tetra-n-butyl ammonium bromide for 50 minutes at room temperature. Then the mixture was treated with a solution of tetra-n-butyl ammonium fluoride in THF (3.5 ml, 3.5 mmol) for 30 minutes at room temperature. Usual work-up (ethyl acetate) gave an crude compound which was subjected to thin-layer preparative chromatography (hexane / ethyl acetate, 4: 1, developed 5 times). The band with the Rf value 0.48 was removed and eluted with ethyl acetate. Removal of the solvent gave the 5,7,22 triene (10) (12.5 mg, 24%), UVA EtOH / max nm: 293, 20,282 and 271.

1α, 25-dihydroxy-22E-dehydro-24-homovitamin-Dg (11)

A solution of 5,7,22-triene (10) (7.3 mg, 0.0143 mmol) in benzene (90 ml) and ethanol (40 ml) was irradiated with a medium-pressure mercury lamp through a Vycor filter at 0 ° C. for 5 minutes under argon. The reaction mixture was heated under argon for 1 hour at reflux. Removal of the solvent under reduced pressure gave an crude compound which was subjected to preparative thin layer chromatography (hexane / ethyl acetate, 4: 1, which was developed 5 times). The band with Rf value 0.38 was removed and eluted with ethyl acetate. Removal of the solvent gave the vitamin D 2 diacetate (1.8 mg, 25%). The band with the Rf value 0.43 was removed and eluted with ethyl acetate. Removal of the solvent recovered the 5,7,22-triene (10) (2.1 mg, 29%).

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Vitamin Dg diacetate (1.8 mg, 2.15 mmol) in THF (4 mL) was treated with 5% KOH / MeOH (1 mL) at room temperature for 20 minutes. Usual work-up (ethyl acetate) gave an crude compound which was subjected to thin-layer preparative chromatography (hexane / ethyl acetate, 1: 2, induced 3 times). The band with the Rf value 0.43 was removed and eluted with ethyl acetate. Removal of the solvent gave the vitamin Dg analog (11) (1.4 mg, 90%). The purity of the compound (11) was determined to 100% by high-pressure liquid chromatography (Shimadzu LC-3A; column Zorbax ZIL normal phase, 4.6 mm internal diameter x 15 cm; solvent MeOH-CH 2 Cl 2, 1:49, flow rate 3 ml / minute ; retention time 11.5 minutes). The vitamin D 2 analog (11) had the following spectral data: UVx EtOH / max: 265 nm, UV \ EtOH / min: 228 nm, 15 MS m / z: 428 (M +), 410, 392 (base peak), 374, 287, 269, 251, 152, 134, 123, 59 1 H-NMR (360 MHz) δ: 0.55 (3H, s, 18-Hg), 1.02 (3H, d, J = 6.6 Hz, 21-H3), 1.22 (6H, s, 26-Hg and 27-H3), 2.32 (1H, dd, J = 13.2 and 6.7 Hz), 2.60 (1H, dd, J = 13.0 and 3.0 Hz), 2.83 (1H, dd, J = 12.0 and 3.0 Hz), 4.23 (1H, m, W1 / 2 = 18.4 Hz, 3 H-4.43 (1H, m, W1 / 2 = 16.9 Hz, 10-H), 5.00 (1H, bs, W1 / 2 = 3.2 Hz, 19-H), 5.30 (1H, dd, J = 15.0 and 7.1 Hz, 22-H or 23-H), 5.33 (1H, bs,

W1 / 2 = 3.2 HZ / 5.37 (1H 'dd' J = 15 '° ° 9 5'8 Hz' 22-H or 23-H), 6.01 (1H, d, J = 11, 0 Hz, 7-H), 6.32 (1H, d, J = 11.0 Hz, 6-H).

1α, 3β-diacetoxy-24-homocholesta-5-en-25-ol (12)

A mixture of 5,22-diene (9) (40 mg, 0.0778 mmol) and 10% Pd-C (4 mg) in ethyl acetate (2 ml) was stirred under hydrogen for 3 hours at room temperature. The Pd catalyst was filtered off and the filtrate was concentrated to give a residue applied to a column of silica gel (5 g). Elution with hexane / ethyl acetate (4: 1) gave 5-ene (12) (37 35 mg, 92%) as an oil. 1 H-NMR δ: 0.66 (3H, s, 18-Hg), 1.08 (3H, s, 19-H3), 1.20 (6H, s, 26-H3 and 27-H3), 2 , 02 (3H, s, acetyl), 2.05 (3H, s, acetyl), 4.97 (1H, m, 3a-H), 5.07 13 (1H, m, 10-H), 5, 53 (1H, m, 6-H).

1α, 3β-dlacetoxy-24-homocholesta-5,7-diene-25-ol (13) The 5-ene (12) (19 mg, 0.037 mmol) was converted as described for compound (9) to 5,7-diene (13) (5.8 mg, 31%). UVX EtOH / max: 293, 282, 271 nm.

1α, 25-dihydroxy-24-homovitamin-Dg (14) 10,7,7-diene (13) (5.8 mg, 0.0113 mmol) was converted as described for compound (10) to the vitamin D 14) (890 µg, 19%). The retention time of (14) under the HPLC conditions described above was 11.0 minutes UVX EtOHmax: 265 nm, UVx EtOH / min: 228 nm. MS m / z: 430 (M +), 412, 394 (base top), 376, 287, 269, 251, 152, 134, 59.

Optionally, the homovitamin compounds can be readily obtained in crystalline form by recrystallization with appropriate solvents such as hexane, ether, alcohol, or mixtures thereof, as will be apparent to those skilled in the art.

25 30 35

Claims (1)

Ch cholestadiene compounds, characterized in that they have the general formula t / OK, or more - in year 15 where R is selected from an acyl group having from 1 to 4 carbon atoms and benzoyl. 20 25 30 35