CN106146592B - 一种合成睾酮方法 - Google Patents
一种合成睾酮方法 Download PDFInfo
- Publication number
- CN106146592B CN106146592B CN201610435623.0A CN201610435623A CN106146592B CN 106146592 B CN106146592 B CN 106146592B CN 201610435623 A CN201610435623 A CN 201610435623A CN 106146592 B CN106146592 B CN 106146592B
- Authority
- CN
- China
- Prior art keywords
- weight ratio
- dissolved
- androstenedione
- testosterone
- potassium borohydride
- 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.)
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- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims abstract description 71
- 229960003604 testosterone Drugs 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 17
- 230000015572 biosynthetic process Effects 0.000 title description 9
- 238000003786 synthesis reaction Methods 0.000 title description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 51
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 24
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims abstract description 24
- 229960005471 androstenedione Drugs 0.000 claims abstract description 24
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 24
- 239000011591 potassium Substances 0.000 claims abstract description 24
- 239000012043 crude product Substances 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 235000019441 ethanol Nutrition 0.000 claims abstract description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000007788 liquid Substances 0.000 claims abstract description 11
- 239000012046 mixed solvent Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 229960000583 acetic acid Drugs 0.000 claims abstract description 7
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 230000002572 peristaltic effect Effects 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 5
- 238000007710 freezing Methods 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000001953 recrystallisation Methods 0.000 abstract description 6
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000012805 post-processing Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- WTLKTXIHIHFSGU-UHFFFAOYSA-N 2-nitrosoguanidine Chemical compound NC(N)=NN=O WTLKTXIHIHFSGU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 230000010718 Oxidation Activity Effects 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 150000001993 dienes Chemical class 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 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 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011426 transformation method Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0018—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa
- C07J1/0022—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0018—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (1)
Priority Applications (1)
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CN201610435623.0A CN106146592B (zh) | 2014-10-08 | 2014-10-08 | 一种合成睾酮方法 |
Applications Claiming Priority (2)
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CN201410523485.2A CN104262439B (zh) | 2014-10-08 | 2014-10-08 | 一种以4-雄烯二酮一步法合成睾酮的方法 |
CN201610435623.0A CN106146592B (zh) | 2014-10-08 | 2014-10-08 | 一种合成睾酮方法 |
Related Parent Applications (1)
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CN201410523485.2A Division CN104262439B (zh) | 2014-10-08 | 2014-10-08 | 一种以4-雄烯二酮一步法合成睾酮的方法 |
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CN106146592A CN106146592A (zh) | 2016-11-23 |
CN106146592B true CN106146592B (zh) | 2017-10-24 |
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Family Applications (6)
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CN201610435766.1A Active CN106188203B (zh) | 2014-10-08 | 2014-10-08 | 一种可提高睾酮的收率及大幅减少杂质的合成睾酮方法 |
CN201610435718.2A Active CN106046091B (zh) | 2014-10-08 | 2014-10-08 | 适于提高睾酮选择性的合成睾酮方法 |
CN201610435623.0A Active CN106146592B (zh) | 2014-10-08 | 2014-10-08 | 一种合成睾酮方法 |
CN201610435716.3A Active CN106188202B (zh) | 2014-10-08 | 2014-10-08 | 副产3,17‑二醇物含量大幅降低的合成睾酮方法 |
CN201610435622.6A Active CN106188201B (zh) | 2014-10-08 | 2014-10-08 | 工艺简单、适于降低还原剂浓度的合成睾酮方法 |
CN201410523485.2A Active CN104262439B (zh) | 2014-10-08 | 2014-10-08 | 一种以4-雄烯二酮一步法合成睾酮的方法 |
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CN201610435766.1A Active CN106188203B (zh) | 2014-10-08 | 2014-10-08 | 一种可提高睾酮的收率及大幅减少杂质的合成睾酮方法 |
CN201610435718.2A Active CN106046091B (zh) | 2014-10-08 | 2014-10-08 | 适于提高睾酮选择性的合成睾酮方法 |
Family Applications After (3)
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CN201610435716.3A Active CN106188202B (zh) | 2014-10-08 | 2014-10-08 | 副产3,17‑二醇物含量大幅降低的合成睾酮方法 |
CN201610435622.6A Active CN106188201B (zh) | 2014-10-08 | 2014-10-08 | 工艺简单、适于降低还原剂浓度的合成睾酮方法 |
CN201410523485.2A Active CN104262439B (zh) | 2014-10-08 | 2014-10-08 | 一种以4-雄烯二酮一步法合成睾酮的方法 |
Country Status (1)
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CN (6) | CN106188203B (zh) |
Families Citing this family (1)
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WO2017093980A1 (en) * | 2015-12-05 | 2017-06-08 | Lupin Limited | Process for preparation of testosterone |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102558267A (zh) * | 2012-01-13 | 2012-07-11 | 宜城市共同药业有限公司 | 庚酸睾酮的制备方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10104327A1 (de) * | 2001-01-24 | 2002-07-25 | Schering Ag | 11beta-Halogensteroide, deren Herstellung und Verwendung zur Herstellung von Arzneimitteln sowie 11beta-Halogensteroide enthaltende pharmazeutische Präparate |
CN103012529A (zh) * | 2012-09-26 | 2013-04-03 | 宜城市共同药业有限公司 | 一种高收率诺龙的合成方法 |
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2014
- 2014-10-08 CN CN201610435766.1A patent/CN106188203B/zh active Active
- 2014-10-08 CN CN201610435718.2A patent/CN106046091B/zh active Active
- 2014-10-08 CN CN201610435623.0A patent/CN106146592B/zh active Active
- 2014-10-08 CN CN201610435716.3A patent/CN106188202B/zh active Active
- 2014-10-08 CN CN201610435622.6A patent/CN106188201B/zh active Active
- 2014-10-08 CN CN201410523485.2A patent/CN104262439B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102558267A (zh) * | 2012-01-13 | 2012-07-11 | 宜城市共同药业有限公司 | 庚酸睾酮的制备方法 |
Non-Patent Citations (1)
Title |
---|
雄烯二酮选择性还原合成睾丸素;郑士辉等;《山东化工》;20110515;第40卷(第5期);第18页左栏1.2以及右栏表3 * |
Also Published As
Publication number | Publication date |
---|---|
CN106046091B (zh) | 2017-08-25 |
CN106046091A (zh) | 2016-10-26 |
CN106188202B (zh) | 2017-10-24 |
CN106188201A (zh) | 2016-12-07 |
CN106188202A (zh) | 2016-12-07 |
CN106188203B (zh) | 2017-10-24 |
CN106188201B (zh) | 2017-10-24 |
CN104262439B (zh) | 2016-06-08 |
CN106188203A (zh) | 2016-12-07 |
CN104262439A (zh) | 2015-01-07 |
CN106146592A (zh) | 2016-11-23 |
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