DE2462000C3 - - Google Patents
Info
- Publication number
- DE2462000C3 DE2462000C3 DE19742462000 DE2462000A DE2462000C3 DE 2462000 C3 DE2462000 C3 DE 2462000C3 DE 19742462000 DE19742462000 DE 19742462000 DE 2462000 A DE2462000 A DE 2462000A DE 2462000 C3 DE2462000 C3 DE 2462000C3
- Authority
- DE
- Germany
- Prior art keywords
- acetoxy
- solution
- acid
- homocholenic
- ether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000002253 acid Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003872 25-hydroxy-cholecalciferol Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- RZPAXNJLEKLXNO-UKNNTIGFSA-N 22R-Hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)C(O)CCC(C)C)[C@@]1(C)CC2 RZPAXNJLEKLXNO-UKNNTIGFSA-N 0.000 description 1
- 235000021318 Calcifediol Nutrition 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L Magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N Trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 229940046008 Vitamin D Drugs 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001749 antrachitic Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Inorganic materials [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
Description
Die Erfindung betrifft zl22-Homocholensäure der "5 FormelThe invention relates to zl 22 -homocholenic acid of the "5 formula
COOHCOOH
HOHO
Diese Verbindung ist ein wichtiges Zwischenprodukt zur Herstellung von 22-Dehydro-25-hydroxycholecalciferol, das eine antirachitische Wirksamkeit besitzt, die wesentlich größer ist als diejenige von Vitamin D3.This compound is an important intermediate in the production of 22-dehydro-25-hydroxycholecalciferol, which has an antirachitic activity that is significantly greater than that of vitamin D 3 .
Die erfindungsgemäße /J22-Homocholensäure kann hergestellt werden aus dem leicht zugänglichen 3/?-Acetoxy-22,23-bisnorcholenaldehyd der FormelThe / J 22 -homocholenic acid according to the invention can be prepared from the easily accessible 3 /? -Acetoxy-22,23-bisnorcholenaldehyde of the formula
AcOAcO
CHOCHO
3535
4040
Die weitere Umsetzung zu dem 22-Dehydro-25-hydroxycholecalciferol wird entsprechend dem folgenden Reaktionsschema durchgeführt:The further conversion to the 22-dehydro-25-hydroxycholecalciferol is carried out according to the following reaction scheme:
COOHCOOH
HOHO
(D(D
COOCH3 COOCH 3
5555
(ID AcO (ID AcO
COOCH3 COOCH 3
COOCH,COOCH,
(IV)(IV)
OHOH
OHOH
OHOH
(VI)(VI)
HOHO
OHOH
(VII)(VII)
= CH= CH
(1"-25-HCC)(1 "-25-HCC)
Der 3ß - Acetoxy - Δ22 - homocholensäure - methylester (III) wird aus I hergestellt durch Methylierung der Carbonsäuregruppe nach dem' Verfahren von Alvarez (F.S.Alvarez und A.N.Watt,The 3ß - acetoxy - Δ 22 - homocholenic acid methyl ester (III) is prepared from I by methylation of the carboxylic acid group according to the 'Alvarez method (FSAlvarez and ANWatt,
J. Org. Chem., 33, 2143 [1968]) für Bisnorcholen-J. Org. Chem., 33, 2143 [1968]) for bisnorcholen-
säure und anschließende Acylierung von II mit Essig- rührt. Nach Zersetzung des überschüssigen Natrium-acid and subsequent acylation of II with vinegar. After decomposition of the excess sodium
säureanhydrid in Pyridin. Es ist vorteilhaft, die 3-Hy- hydrids mit einer kleinen Menge Methanol wurdeacid anhydride in pyridine. It is beneficial to use the 3-hy- hydrids with a small amount of methanol
droxv-Stellung vor der Bromierung durch Bildung das Reaktionsgemisch in Wasser gegossen. Das ronedroxv position before bromination by forming the reaction mixture poured into water. The rone
des Acetats zu schützen. Produkt wurde durch Extraktion mit Benzol entfernt,of the acetate to protect. Product was removed by extraction with benzene,
Die Bromierung von III mit l,3-Dibrom-5,5-di- 5 das nacheinander mit Wasser und gesättigter Na-The bromination of III with 1,3-dibromo-5,5-di- 5 which is successively mixed with water and saturated Na-
methylhydantoin und anschließende Dehydrohalo- triumchloridlösung gewaschen und dann über was-methylhydantoin and subsequent dehydrohalotrium chloride solution and then washed over
eenierung mit Trimethylphosphit nach dem Ver- serfreiem Natriumsulfat getrocknet wurde,eenierung with trimethyl phosphite after the non-performing sodium sulfate was dried,
fahren von Hunziker und Mullner (HeIv. Der Hauptanteil des Triphenylphosphidoxids wurdedrive by Hunziker and Mullner (HeIv. The main part of the triphenylphosphidoxide was
Chim Acta, 41, 70 [1958]) ergibt ein Gemisch der durch Lösungsmittelverteilung entfernt. Das roneChim Acta, 41, 70 [1958]) gives a mixture which is removed by solvent distribution. The rone
™_und ^-"-Isomere. D|s ^.«-isomer (IV) ,o Produkt wurde in 140cm3 Methanol, enthaltend™ _ and ^ - "- isomers. D | s ^.« - isomer (IV), o Product was contained in 140cm 3 of methanol
wird von dem ^6-2Msomer durch fraktionierte Kri- 20 cm3 5%ige Natriumhydroxidlosung gelost Dieis of the ^ 6 - 2 Msomer by fractional crisis 20 cm 3 of 5% dissolved Natriumhydroxidlosung The
stellisation abgetrennt. Lösung wurde zunächst mit 200 cm3 Diathyl-ätherStellization separated. Solution was initially with 200 cm 3 of diethyl ether
Behandlung des ^-'-"-Homoesters (IV) mit Methyl- und dann mit 200 cm4 Wasser vermischt. Die Atner-Treatment of the ^ -'- "- homoester (IV) with methyl and then mixed with 200 cm 4 of water.
magnesiumbromid ergibt das erwartete 7-Dehydro- schicht wurde verworfen und die 3 w^rfe ™J°;magnesium bromide gives the expected 7-dehydro- layer was discarded and the 3 w ^ r f e ™ J °;
J22-25-hydroxycholesterol (V). Bei UV-Bestrahlung .5 lösung weiter mit 2mal je 200 cm Äther gewaschenJ 22-hydroxycholesterol -25 (V). In the case of UV irradiation .5 the solution is further washed with 2 times 200 cm of ether each time
von V bei 300nm in Athanol-Äther-Lösung erhält Die alkalische Lösung ™rd„c.^J^0™ .jg^of V at 300nm in ethanol-ether solution, the alkaline solution ™ rd " c . ^ J ^ 0 ™ .jg ^
man die provitamin-D-artige Verbindung Pro- verdünnt und nut 25 cm3 20%ige S^f™the provitamin-D-like compound Pro- is diluted and only 25 cm 3 of 20% S ^ f ™
^2-25-hydroxycho!ecalcifen>l (VI), die nach der Iso- angesäuert. Das rohe Produkt wurde mit Äther^ 2 -25-hydroxycho! Ecalcifen> l (VI) acidified by the iso. The raw product was made with ether
merisierung Λ22 - 25 - Hydroxycholecalciferol (VII) extrahiert. Das Produkt wurde durch Umknstah-merization Λ 22 - 25 - Hydroxycholecalciferol (VII) extracted. The product has been
St >° sieren aus Methanol gereinigt. Die Ausbeute betrugSt> ° sieren cleaned from methanol. The yield was
Die Herstellung von J22-Homocholensäure wird ungefähr 80%, bezogen auf das Aldehyd. Das Intraro-The production of J 22 homocholenic acid is about 80% based on the aldehyde. The intraro
durch das folgende Beispiel näher erläutert. spektrum (KBr) der Substanz besaß eine Carbonyl-explained in more detail by the following example. spectrum (KBr) of the substance had a carbonyl
durcn aa» β ν absorption bei 5,88 H.m und stimmte sonst mit derdurcn aa »β ν absorption at 5.88 H .m and otherwise agreed with the
Beispiel angegebenen Struktur überein. Es war keine Acetoxy-The structure given in the example. It wasn't an acetoxy
Eine Lösung aus 5,2 g (14 mMol) 3/3-Acetoxy- 25 absorption vorhanden.A solution of 5.2 g (14 mmol) of 3/3-acetoxy absorption is present.
22,23-bisnorcholenaldehyd (I) und 7,5 g (18 mMol) A . rür c„H«Oa:22,23-bisnorcholenaldehyde (I) and 7.5 g (18 mmol) of A. r for c "H" O a :
2 - Carboxyäthyltriphenylphosphonium - bromid in Analyse tür L25I-I38U ^2 - Carboxyäthyltriphenylphosphonium - bromid in analysis for L 25 II 38 U ^
80 cm3 eines trockenen Dimethylsulfoxid- Toluol- Berechnet ... C 7 7,67,H y,yi,80 cm 3 of a dry dimethyl sulfoxide- toluene- Calculated ... C 7 7.67, H y, yi,
Gemisches (1:1) wurde auf ungefähr 50C abgekühlt gefunden C 78,08, H 1U.14.Mixture (1: 1) was cooled to about 5 0 C found C 78.08, H 1U.14.
und schnell unter gutem Rühren zu einer gekühlten 30 . . M and quickly with good stirring to a chilled 30. . M.
Suspension (Eisbad) von 1,04 g (43,3 mMol) Na- Das Molekulargewicht von 386 wurde durch Mas-Suspension (ice bath) of 1.04 g (43.3 mmol) Na- The molecular weight of 386 was determined by mass
SKdrid in 10 cm3 trockenem Toluol gegeben. senspektroskopie bestimmt. Die Gasflussigkeitschro-SKdrid given in 10 cm 3 of dry toluene. determined by spectroscopy. The gas liquid
Sfe Zugabe und anschließende Umsetzung wurde matographie (GLC-Analyse) zeigt das Vorhandeo-Sfe addition and subsequent implementation was matography (GLC analysis) shows the presence of
unter trockenem Stickstoff durchgeführt. Das Reak- sein der beiden Α22-ά%- und trans-Isomere in e.nemcarried out under dry nitrogen. The reactivity of the two Α 22 % and trans isomers in e.nem
tionsgemisch wurde 16 h bei Raumtemperatur ge- 35 Verhältnis von ungefähr 1:4 an.The mixture was stirred at room temperature for 16 hours at a ratio of approximately 1: 4.
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33288273A | 1973-02-16 | 1973-02-16 | |
| US33288273 | 1973-02-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2462000A1 DE2462000A1 (en) | 1975-10-09 |
| DE2462000B2 DE2462000B2 (en) | 1976-12-30 |
| DE2462000C3 true DE2462000C3 (en) | 1977-08-25 |
Family
ID=23300266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742462000 Granted DE2462000B2 (en) | 1973-02-16 | 1974-02-14 | DELTA HIGH 22-HOMOCHOLIC ACID AND PROCESS FOR THEIR PRODUCTION |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3786062A (en) |
| JP (2) | JPS5324940B2 (en) |
| BE (1) | BE811097A (en) |
| CA (1) | CA1021802A (en) |
| DE (1) | DE2462000B2 (en) |
| FR (1) | FR2218087B1 (en) |
| GB (2) | GB1437661A (en) |
| NL (1) | NL7402123A (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3963765A (en) * | 1973-04-01 | 1976-06-15 | Yehuda Mazur | Preparation of derivatives of cholesterol |
| US3922291A (en) * | 1974-02-14 | 1975-11-25 | Wisconsin Alumni Res Found | 22-Dehydro-homocholenic acid |
| US4172076A (en) * | 1977-04-04 | 1979-10-23 | Diamond Shamrock Corporation | Process for preparing steroidal acids and their intermediate derivatives |
| US4145346A (en) * | 1977-10-03 | 1979-03-20 | Merck & Co., Inc. | Preparation of 3β-hydroxy-27-norcholest-5-ene-25-one and intermediates thereof |
| US4360471A (en) * | 1981-12-11 | 1982-11-23 | Wisconsin Alumni Research Foundation | 23-Dehydro-25-hydroxyvitamin D3 |
| US4588528A (en) * | 1984-05-31 | 1986-05-13 | Wisconsin Alumni Research Foundation | 1,24-dihydroxy-Δ22 -vitamin D3 and process for preparing same |
| US4868206A (en) * | 1985-12-06 | 1989-09-19 | Ici Americas Inc. | Composition for rodent control |
| US7253293B2 (en) * | 2004-01-06 | 2007-08-07 | Andrzej Slominski | Enzymatic method to produce 7-dehydropregnenolone, vitamin D3-like compounds and derivatives thereof |
-
1973
- 1973-02-16 US US00332882A patent/US3786062A/en not_active Expired - Lifetime
-
1974
- 1974-02-04 CA CA191,670A patent/CA1021802A/en not_active Expired
- 1974-02-12 GB GB637874A patent/GB1437661A/en not_active Expired
- 1974-02-12 GB GB2963675A patent/GB1437662A/en not_active Expired
- 1974-02-14 DE DE19742462000 patent/DE2462000B2/en active Granted
- 1974-02-15 NL NL7402123A patent/NL7402123A/xx not_active Application Discontinuation
- 1974-02-15 FR FR7405297A patent/FR2218087B1/fr not_active Expired
- 1974-02-15 BE BE140968A patent/BE811097A/en not_active IP Right Cessation
- 1974-02-15 JP JP1845174A patent/JPS5324940B2/ja not_active Expired
-
1977
- 1977-12-08 JP JP14665877A patent/JPS5384958A/en active Granted
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