SU1447826A1 - Способ получени 11 @ -гидроксистероидов прегнанового р да - Google Patents

Способ получени 11 @ -гидроксистероидов прегнанового р да Download PDF

Info

Publication number: SU1447826A1
Authority: SU; USSR - Soviet Union
Prior art keywords: hydroxy; ether; solution; triamcinolone; group
Prior art date: 1982-10-01

Application number

SU837773084A

Other languages

English (en)

Russian (ru)

Inventor

Лангбейн Герхард

Зимани Ганс-Йоахим

Шварц Зигфрид

Менцер Эльфриде

Грунер Ингрид

Грейнер Хельга

Original Assignee

"Йенафарм" (Инопредприятие)

Priority date (The priority date 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 date listed.)

1982-10-01

Filing date

1983-08-22

Publication date

1988-12-30

1983-08-22 Application filed by "Йенафарм" (Инопредприятие) filed Critical "Йенафарм" (Инопредприятие)

1988-12-30 Application granted granted Critical

1988-12-30 Publication of SU1447826A1 publication Critical patent/SU1447826A1/ru

Links

150000003128 pregnanes Chemical class 0.000 title claims abstract description 7
238000000034 method Methods 0.000 title claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
-1 dihydropyranyl ethers Chemical class 0.000 claims abstract description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 4
229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
239000011737 fluorine Substances 0.000 claims abstract description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
239000002253 acid Substances 0.000 claims description 4
238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
238000010511 deprotection reaction Methods 0.000 claims 1
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 abstract description 15
230000015572 biosynthetic process Effects 0.000 abstract description 14
238000002360 preparation method Methods 0.000 abstract description 9
229960000890 hydrocortisone Drugs 0.000 abstract description 8
238000003786 synthesis reaction Methods 0.000 abstract description 6
239000000126 substance Substances 0.000 abstract description 4
239000000543 intermediate Substances 0.000 abstract description 3
229960005205 prednisolone Drugs 0.000 abstract description 3
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 abstract description 3
150000001875 compounds Chemical class 0.000 abstract description 2
229940079593 drug Drugs 0.000 abstract description 2
239000003814 drug Substances 0.000 abstract description 2
238000004519 manufacturing process Methods 0.000 abstract description 2
239000007858 starting material Substances 0.000 abstract description 2
150000003431 steroids Chemical class 0.000 abstract description 2
230000002378 acidificating effect Effects 0.000 abstract 1
230000002427 irreversible effect Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
229960005294 triamcinolone Drugs 0.000 description 17
GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
150000002148 esters Chemical class 0.000 description 12
238000005406 washing Methods 0.000 description 12
238000007127 saponification reaction Methods 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
238000003756 stirring Methods 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
238000001035 drying Methods 0.000 description 6
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 6
230000035484 reaction time Effects 0.000 description 6
239000000203 mixture Substances 0.000 description 5
238000000926 separation method Methods 0.000 description 5
235000011121 sodium hydroxide Nutrition 0.000 description 5
238000003797 solvolysis reaction Methods 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
230000007017 scission Effects 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000000605 extraction Methods 0.000 description 3
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
150000001242 acetic acid derivatives Chemical class 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
230000006735 deficit Effects 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
238000004299 exfoliation Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 2
235000011118 potassium hydroxide Nutrition 0.000 description 2
229960004618 prednisone Drugs 0.000 description 2
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 2
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
IOOGIWIGKUAFIY-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethenoxy)ethene Chemical compound CCOC=COC=COCC IOOGIWIGKUAFIY-UHFFFAOYSA-N 0.000 description 1
VHRSUDSXCMQTMA-UWKORSIYSA-N 6-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1C(C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-UWKORSIYSA-N 0.000 description 1
QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000003513 alkali Substances 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
229960001347 fluocinolone acetonide Drugs 0.000 description 1
FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
229960001067 hydrocortisone acetate Drugs 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1

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Steroid Compounds (AREA)

SU837773084A 1982-10-01 1983-08-22 Способ получени 11 @ -гидроксистероидов прегнанового р да SU1447826A1 (ru)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DD24370082A DD225595A3 (de)	1982-10-01	1982-10-01	Verfahren zur herstellung von 11 beta-hydroxysteroiden aus 11 beta-acyloxysteroiden

Publications (1)

Publication Number	Publication Date
SU1447826A1 true SU1447826A1 (ru)	1988-12-30

Family

ID=5541543

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SU837773084A SU1447826A1 (ru)	1982-10-01	1983-08-22	Способ получени 11 @ -гидроксистероидов прегнанового р да

Country Status (3)

Country	Link
BG (1)	BG46375A1 (de)
DD (1)	DD225595A3 (de)
SU (1)	SU1447826A1 (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2127278C1 (ru) *	1993-01-20	1999-03-10	Руссель-Юклаф	СПОСОБ ПОЛУЧЕНИЯ 16α--МЕТИЛИРОВАННЫХ СТЕРОИДОВ

1982
- 1982-10-01 DD DD24370082A patent/DD225595A3/de not_active IP Right Cessation
1983
- 1983-08-22 SU SU837773084A patent/SU1447826A1/ru active
- 1983-08-24 BG BG6218883A patent/BG46375A1/xx unknown

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2127278C1 (ru) *	1993-01-20	1999-03-10	Руссель-Юклаф	СПОСОБ ПОЛУЧЕНИЯ 16α--МЕТИЛИРОВАННЫХ СТЕРОИДОВ

Also Published As

Publication number	Publication date
BG46375A1 (en)	1989-12-15
DD225595A3 (de)	1985-07-31

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SU1447826A1 - Способ получени 11 @ -гидроксистероидов прегнанового р да - Google Patents

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Applications Claiming Priority (1)

Publications (1)

Family

ID=5541543

Family Applications (1)

Country Status (3)

Cited By (1)

Cited By (1)

Also Published As

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