CN105693684B - 一种异佛司可林的制备方法 - Google Patents
一种异佛司可林的制备方法 Download PDFInfo
- Publication number
- CN105693684B CN105693684B CN201610044817.8A CN201610044817A CN105693684B CN 105693684 B CN105693684 B CN 105693684B CN 201610044817 A CN201610044817 A CN 201610044817A CN 105693684 B CN105693684 B CN 105693684B
- Authority
- CN
- China
- Prior art keywords
- isoforskolin
- preparation
- solvent
- reaction
- purity
- 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.)
- Active
Links
- CLOQVZCSBYBUPB-KGGHGJDLSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-5,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-6-yl] acetate Chemical compound O[C@H]([C@@]12C)CCC(C)(C)[C@@H]1[C@H](OC(=O)C)[C@H](O)[C@]1(C)[C@]2(O)C(=O)C[C@](C)(C=C)O1 CLOQVZCSBYBUPB-KGGHGJDLSA-N 0.000 title claims abstract description 140
- SBMKZIAQTQIEHN-NRADYMPXSA-N Coleonol C Natural products [H][C@@]12[C@H](OC(C)=O)[C@@H](O)[C@@]3(C)O[C@@](C)(CC(=O)[C@]3(O)[C@@]1(C)[C@@H](C)CCC2(C)C)C=C SBMKZIAQTQIEHN-NRADYMPXSA-N 0.000 title claims abstract description 70
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 56
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 238000002425 crystallisation Methods 0.000 claims abstract description 19
- 230000008025 crystallization Effects 0.000 claims abstract description 19
- 239000012043 crude product Substances 0.000 claims abstract description 13
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 claims abstract description 11
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 7
- 238000006462 rearrangement reaction Methods 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 35
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 17
- 238000005406 washing Methods 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 18
- 239000003208 petroleum Substances 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000131459 Plectranthus barbatus Species 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000004140 cleaning Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 235000005320 Coleus barbatus Nutrition 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000004575 stone Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 235000021508 Coleus Nutrition 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 230000036632 reaction speed Effects 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000005815 base catalysis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229930002697 labdane diterpene Natural products 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
反应溶剂 | 反应情况 | 反应时间 | 收率 |
二氯甲烷 | 反应较快 | 48-72h以后不再有产物生成,反应完成 | 53% |
四氢呋喃 | 反应非常缓慢 | 反应至72h仅有少量目标产物生成。 | / |
甲醇 | 反应非常缓慢 | 反应至72h仅有少量目标产物生成。 | / |
乙醇 | 反应非常缓慢 | 反应至72h仅有少量目标产物生成。 | / |
苯 | 反应较慢 | 120h以后不再有产物生成,反应完成。 | 55% |
Min | A(%) | B(%) |
0 | 95 | 5 |
2 | 95 | 5 |
5 | 70 | 30 |
20 | 25 | 75 |
30 | 5 | 95 |
Claims (8)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610044817.8A CN105693684B (zh) | 2016-01-22 | 2016-01-22 | 一种异佛司可林的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610044817.8A CN105693684B (zh) | 2016-01-22 | 2016-01-22 | 一种异佛司可林的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105693684A CN105693684A (zh) | 2016-06-22 |
CN105693684B true CN105693684B (zh) | 2018-10-09 |
Family
ID=56228491
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610044817.8A Active CN105693684B (zh) | 2016-01-22 | 2016-01-22 | 一种异佛司可林的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105693684B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105601516B (zh) * | 2016-03-31 | 2017-07-07 | 河南中医学院 | 一种从小叶莲中提取分离的半日花烷型二萜类化合物及其制备方法与应用 |
CN106596797B (zh) * | 2017-01-19 | 2020-04-21 | 湖北福人药业股份有限公司 | 鞘蕊苏胶囊的含量测定 |
CN111548334B (zh) * | 2020-04-29 | 2022-03-29 | 广东省肇庆华格生物科技有限公司 | 一种乙基麦芽酚的合成工艺 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU591196B2 (en) * | 1985-11-15 | 1989-11-30 | Nippon Kayaku Kabushiki Kaisha | Novel forskolin derivatives |
DE3887212T2 (de) * | 1987-06-29 | 1994-06-01 | Nippon Kayaku Kk | Verfahren zur Herstellung von Derivaten von 6,7-Diazyl-7-desacetylforskolin. |
JP2007210988A (ja) * | 2006-02-07 | 2007-08-23 | Sabinsa Corp | ジテルペンフォルスコリン及びその誘導体で男性ホルモン及び女性ホルモンを生理学的に増大するための組成物 |
CN103123340B (zh) * | 2011-11-18 | 2014-07-09 | 复旦大学 | 一种测定毛喉鞘蕊花中半日花烷型二萜的方法 |
CN103183658A (zh) * | 2011-12-29 | 2013-07-03 | 复旦大学 | 一种提取毛喉鞘蕊花有效成分的方法 |
-
2016
- 2016-01-22 CN CN201610044817.8A patent/CN105693684B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN105693684A (zh) | 2016-06-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110357853B (zh) | (r,s-)尼古丁的合成方法 | |
CN105693684B (zh) | 一种异佛司可林的制备方法 | |
CN102002082B (zh) | 一种黄芩苷的制备方法 | |
CN105859670B (zh) | 一种高纯度丁苯酞的制备方法 | |
CN111072589B (zh) | 米拉贝隆的重结晶方法和制备方法 | |
JP2017520616A (ja) | 杜仲葉からクロロゲン酸を抽出する方法 | |
CN104628801B (zh) | 一种从野菊花中提取分离蒙花苷工艺 | |
CN113999167B (zh) | 一种4-氯-2,6-二甲基-3-硝基吡啶的制备方法 | |
CN106905339B (zh) | 一种从连翘叶中提纯连翘苷元的方法 | |
WO2007083908A1 (en) | A method for preparing decursinol from angelica gigas with high yield | |
CN107033114A (zh) | 一种二氢杨梅素的分离纯化方法 | |
CN110256389B (zh) | 莨菪亭的制备方法 | |
CN104892551B (zh) | 一种从红豆杉枝叶中分离提纯10-去乙酰基巴卡亭iii的方法 | |
CN107141272A (zh) | 一种半合成多西他赛方法及其中间体 | |
CN107739307B (zh) | 一种用稀碱溶液提取-固相萃取柱纯化原儿茶酸的方法 | |
CN113717135A (zh) | 羰基取代的苯并二氢呋喃、苯并二氢吡喃化合物的合成方法 | |
CN106117281B (zh) | 从红景天中提取红景天苷的方法 | |
CN105837645B (zh) | 从油茶叶中提取3-甲氧基鞣花酸-4-O-β-D-葡萄糖苷的方法 | |
CN101270119A (zh) | 一种从豆科棘豆属或黄芪属植物中提纯苦马豆素的工艺 | |
CN113754715B (zh) | (5r)-5-羟基雷公藤内酯醇的光学选择性工艺合成方法 | |
CN114014860B (zh) | 一种制备生物碱hosieineA的方法 | |
CN105777542A (zh) | 一种柠檬酸三乙酯纯化的方法 | |
CN113234073B (zh) | 一种吡喹酮杂质b的制备方法 | |
CN113582920B (zh) | 一种4-(4-吡啶基)吗啉的合成方法 | |
CN114014900B (zh) | 一种从野菊花茎秆中提取分离蒙花苷的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20230727 Address after: Floor 14, Wolin Building, No. 285, Xinguang Lane, High tech Zone, Kunming, Yunnan 650101 Patentee after: SHURELI BIOPHARMA Co.,Ltd. Address before: No. 1168, Chunrong West Road, Yuhua street, Chenggong New Town, Kunming, Yunnan 650500 Patentee before: KUNMING MEDICAL University |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240115 Address after: No. 416-4, South Wing Office Building, Building A, High tech Electronic Industry Standard Factory, No. 1520 Haiyuan Middle Road, High tech Zone, Kunming City, Yunnan Province, 650101 Patentee after: Yunnan Hebo Biomedical Technology Co.,Ltd. Address before: Floor 14, Wolin Building, No. 285, Xinguang Lane, High tech Zone, Kunming, Yunnan 650101 Patentee before: SHURELI BIOPHARMA Co.,Ltd. |