CA2347345A1 - Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bonds - Google Patents
Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bondsInfo
- Publication number
- CA2347345A1 CA2347345A1 CA002347345A CA2347345A CA2347345A1 CA 2347345 A1 CA2347345 A1 CA 2347345A1 CA 002347345 A CA002347345 A CA 002347345A CA 2347345 A CA2347345 A CA 2347345A CA 2347345 A1 CA2347345 A1 CA 2347345A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alpha
- hydroxyalkyl
- epoxidation
- carboxyl
- 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.)
- Granted
Links
- 239000000543 intermediate Substances 0.000 title abstract 2
- 238000000034 method Methods 0.000 title abstract 2
- 239000004593 Epoxy Substances 0.000 title 1
- 238000006735 epoxidation reaction Methods 0.000 title 1
- 230000008570 general process Effects 0.000 title 1
- 230000008569 process Effects 0.000 title 1
- 150000003431 steroids Chemical class 0.000 title 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 3
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 3
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 125000004104 aryloxy group Chemical group 0.000 abstract 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 3
- 125000001475 halogen functional group Chemical group 0.000 abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract 3
- 239000001257 hydrogen Substances 0.000 abstract 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 3
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 abstract 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 abstract 2
- 125000002837 carbocyclic group Chemical group 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 abstract 1
- 229960001208 eplerenone Drugs 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/001—Lactones
- C07J21/003—Lactones at position 17
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
- C07J71/0015—Oxiranes at position 9(11)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
- C12P33/005—Degradation of the lateral chains at position 17
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
- C12P33/06—Hydroxylating
- C12P33/08—Hydroxylating at 11 position
- C12P33/10—Hydroxylating at 11 position at 11 alpha-position
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I
(see formula I) wherein:
-A-A- represents the group -CHR4-CHR5- or -CR7=CR5-R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, aryloxy, R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical, -B-B- represents the group -CHR6-CHR7- or an alpha-or beta- oriented group:
(see formula III) where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, and R8 and R9 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
(see formula I) wherein:
-A-A- represents the group -CHR4-CHR5- or -CR7=CR5-R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, aryloxy, R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical, -B-B- represents the group -CHR6-CHR7- or an alpha-or beta- oriented group:
(see formula III) where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, and R8 and R9 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US845595P | 1995-12-11 | 1995-12-11 | |
| US60/008,455 | 1995-12-11 | ||
| PCT/US1996/020780 WO1997021720A2 (en) | 1995-12-11 | 1996-12-11 | Processes for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olifinic double bonds |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2240388 Division CA2240388A1 (en) | 1995-12-11 | 1996-12-11 | Processes for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olifinic double bonds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2347345A1 true CA2347345A1 (en) | 1997-06-19 |
| CA2347345C CA2347345C (en) | 2007-05-15 |
Family
ID=21731702
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002347345A Expired - Fee Related CA2347345C (en) | 1995-12-11 | 1996-12-11 | Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bonds |
| CA002347346A Expired - Fee Related CA2347346C (en) | 1995-12-11 | 1996-12-11 | Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bonds |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002347346A Expired - Fee Related CA2347346C (en) | 1995-12-11 | 1996-12-11 | Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bonds |
Country Status (5)
| Country | Link |
|---|---|
| KR (3) | KR100523146B1 (en) |
| CN (1) | CN1903872A (en) |
| AU (1) | AU719260B2 (en) |
| CA (2) | CA2347345C (en) |
| HU (1) | HU222453B1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844681B (en) * | 2014-02-13 | 2016-06-01 | 合肥久诺医药科技有限公司 | The process for purification of the brilliant type eplerenone of a kind of L |
| CN111505238A (en) * | 2019-01-31 | 2020-08-07 | 中国石油化工股份有限公司 | Rock cloudization computing method and computing system |
| CN110698529A (en) * | 2019-11-19 | 2020-01-17 | 湖南新合新生物医药有限公司 | Preparation method of eplerenone intermediate △ 9,11 alkenyl ester |
| CN111593086B (en) * | 2020-05-27 | 2023-05-05 | 湖北葛店人福药业有限责任公司 | Method for reducing impurities in ethyldiketone 11a hydroxylation process by using mixed solvent |
-
1996
- 1996-12-11 HU HU9900493A patent/HU222453B1/en not_active IP Right Cessation
- 1996-12-11 KR KR10-2004-7011499A patent/KR100523146B1/en not_active IP Right Cessation
- 1996-12-11 AU AU13551/97A patent/AU719260B2/en not_active Ceased
- 1996-12-11 CA CA002347345A patent/CA2347345C/en not_active Expired - Fee Related
- 1996-12-11 KR KR1020057012628A patent/KR100579527B1/en not_active IP Right Cessation
- 1996-12-11 CN CNA2006100681395A patent/CN1903872A/en active Pending
- 1996-12-11 KR KR10-1998-0704395A patent/KR100523227B1/en not_active IP Right Cessation
- 1996-12-11 CA CA002347346A patent/CA2347346C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR100579527B1 (en) | 2006-05-12 |
| AU1355197A (en) | 1997-07-03 |
| KR100523146B1 (en) | 2005-10-24 |
| AU719260B2 (en) | 2000-05-04 |
| HU222453B1 (en) | 2003-07-28 |
| CA2347346A1 (en) | 1997-06-19 |
| KR20050085950A (en) | 2005-08-29 |
| CA2347345C (en) | 2007-05-15 |
| CN1903872A (en) | 2007-01-31 |
| KR19990076572A (en) | 1999-10-15 |
| HUP9900493A2 (en) | 1999-05-28 |
| HUP9900493A3 (en) | 1999-11-29 |
| KR20040071782A (en) | 2004-08-12 |
| CA2347346C (en) | 2007-01-02 |
| KR100523227B1 (en) | 2005-12-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |