CN101928309B - 3,2’,6’-三-N-乙酰基庆大霉素C1a的合成方法 - Google Patents
3,2’,6’-三-N-乙酰基庆大霉素C1a的合成方法 Download PDFInfo
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- CN101928309B CN101928309B CN201010132460.1A CN201010132460A CN101928309B CN 101928309 B CN101928309 B CN 101928309B CN 201010132460 A CN201010132460 A CN 201010132460A CN 101928309 B CN101928309 B CN 101928309B
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- Prior art keywords
- gentamicinc
- ethanoyl
- compound method
- reaction
- tri
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 229930182566 Gentamicin Natural products 0.000 title abstract 4
- 229960002518 gentamicin Drugs 0.000 title abstract 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000011701 zinc Substances 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000004246 zinc acetate Substances 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 238000013375 chromatographic separation Methods 0.000 claims abstract description 5
- 239000011259 mixed solution Substances 0.000 claims abstract description 5
- 239000008213 purified water Substances 0.000 claims abstract description 5
- 239000000470 constituent Substances 0.000 claims abstract description 4
- 238000004821 distillation Methods 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims description 11
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 238000011010 flushing procedure Methods 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 2
- 238000005406 washing Methods 0.000 abstract description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 abstract 2
- 238000001816 cooling Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 abstract 1
- 238000007710 freezing Methods 0.000 abstract 1
- 230000008014 freezing Effects 0.000 abstract 1
- VEGXETMJINRLTH-BOZYPMBZSA-N gentamycin C1a Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-BOZYPMBZSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000005070 sampling Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 6
- -1 Amino Chemical group 0.000 description 4
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 3
- 241000545067 Venus Species 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229910001429 cobalt ion Inorganic materials 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
乙酸酐与庆大霉素C1a的摩尔比 | 收率 | |
实施例1 | 4.5∶1 | 93.9% |
实施例2 | 5∶1 | 93.6% |
实施例3 | 4∶1 | 90.2% |
实施例4 | 3.5∶1 | 87.9% |
实施例5 | 3∶1 | 85.4% |
过渡金属醋酸盐 | 收率 | 纯度 | |
实施例1 | 乙酸锌 | 93.9% | 92.0% |
对比例1 | 乙酸钴 | 84.2% | 90.0% |
对比例2 | 乙酸铜 | 79.5% | 88.9% |
溶剂 | 收率 | 纯度 | |
实施例1 | 甲醇 | 93.9% | 92.0% |
对比例3 | 水 | 71.6% | 86.5% |
对比例4 | N,N’-二甲基甲酰胺 | 80.1% | 88.3% |
对比例5 | 二甲亚砜 | 81.2% | 90.0% |
Claims (8)
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CN201010132460.1A CN101928309B (zh) | 2010-03-26 | 2010-03-26 | 3,2’,6’-三-N-乙酰基庆大霉素C1a的合成方法 |
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CN201010132460.1A CN101928309B (zh) | 2010-03-26 | 2010-03-26 | 3,2’,6’-三-N-乙酰基庆大霉素C1a的合成方法 |
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CN101928309A CN101928309A (zh) | 2010-12-29 |
CN101928309B true CN101928309B (zh) | 2012-10-10 |
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Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103374047B (zh) * | 2012-04-27 | 2016-05-11 | 无锡济民可信山禾药业股份有限公司 | 一种高纯度的3,2″,6″-三-N-乙酰基庆大C1a碱(P1)分离纯化方法 |
CN102746349B (zh) * | 2012-06-27 | 2014-07-30 | 常州方圆制药有限公司 | 一种硫酸依替米星中间体3,2’,6’-三-N-乙酰基庆大霉素Cla的合成方法 |
CN102735780B (zh) * | 2012-06-27 | 2014-07-30 | 常州方圆制药有限公司 | 一种监测3,2’,6’-三-N-乙酰基庆大霉素Cla含量的方法 |
CN103524577B (zh) * | 2013-09-30 | 2016-01-13 | 无锡济民可信山禾药业股份有限公司 | 一种硫酸依替米星中间体(3,2’,6’-三-N-乙酰基庆大霉素C1a)的合成方法 |
CN103641869B (zh) * | 2013-12-30 | 2016-04-06 | 广州自远生物科技有限公司 | 一种泰拉菌素的合成方法 |
WO2017002955A1 (ja) * | 2015-07-02 | 2017-01-05 | 日産化学工業株式会社 | シクロデキストリン誘導体の製造方法、及びその重合体 |
CN108129527B (zh) * | 2018-01-11 | 2020-03-20 | 中国医药集团总公司四川抗菌素工业研究所 | 依替米星衍生物及其制备方法、其药物组合物和应用 |
CN109438527A (zh) * | 2018-09-20 | 2019-03-08 | 无锡济民可信山禾药业股份有限公司 | 一种从硫酸依替米星中间体合成副产物中回收庆大霉素C1a的方法 |
CN109096347B (zh) * | 2018-09-20 | 2022-03-08 | 无锡济煜山禾药业股份有限公司 | 一种高纯度的3,2`,6`-三-N-乙酰基庆大C1a碱(P1)纯化方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1100467A (zh) * | 1993-04-23 | 1995-03-22 | 江苏省微生物研究所 | 1-n-乙基庆大霉素衍生物及其制备方法 |
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- 2010-03-26 CN CN201010132460.1A patent/CN101928309B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1100467A (zh) * | 1993-04-23 | 1995-03-22 | 江苏省微生物研究所 | 1-n-乙基庆大霉素衍生物及其制备方法 |
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Denomination of invention: Synthesis of 3,2 ', 6' - tri-n-acetylgentamicin C1a Effective date of registration: 20200925 Granted publication date: 20121010 Pledgee: Agricultural Development Bank of China Chifeng Yuanbaoshan sub branch Pledgor: CHANGZHOU FANGYUAN PHARMACEUTICAL Co.,Ltd.|INNER MONGOLIA PUYIN PHARMACEUTICAL Co.,Ltd. Registration number: Y2020150000058 |
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