CN103172686A - 克拉霉素-n-氧化物的制备方法 - Google Patents
克拉霉素-n-氧化物的制备方法 Download PDFInfo
- Publication number
- CN103172686A CN103172686A CN201310118982XA CN201310118982A CN103172686A CN 103172686 A CN103172686 A CN 103172686A CN 201310118982X A CN201310118982X A CN 201310118982XA CN 201310118982 A CN201310118982 A CN 201310118982A CN 103172686 A CN103172686 A CN 103172686A
- Authority
- CN
- China
- Prior art keywords
- clarithromycin
- oxide compound
- reaction
- hydrogen peroxide
- peroxide solution
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- KDRPFIWYMNONLJ-KCBOHYOISA-N (2s,3r,4s,6r)-2-[[(3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-14-ethyl-12,13-dihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-3-hydroxy-n,n,6-trimethyloxan-4-amine ox Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)[N+](C)(C)[O-])O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 KDRPFIWYMNONLJ-KCBOHYOISA-N 0.000 title abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229960002626 clarithromycin Drugs 0.000 claims abstract description 31
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000001953 recrystallisation Methods 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 5
- -1 clarithromycin-N-oxide compound Chemical class 0.000 claims description 34
- 239000013078 crystal Substances 0.000 claims description 16
- 239000012043 crude product Substances 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 9
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 6
- 239000006210 lotion Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 3
- 239000012535 impurity Substances 0.000 abstract description 13
- 239000000047 product Substances 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 3
- 230000009466 transformation Effects 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 2
- 238000001035 drying Methods 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 8
- 229960003276 erythromycin Drugs 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 0 CCC(CCCC(CC(C([C@](C1*C1)C(*)C(C)CC1=C)=C)*#*)=*)C1=N Chemical compound CCC(CCCC(CC(C([C@](C1*C1)C(*)C(C)CC1=C)=C)*#*)=*)C1=N 0.000 description 3
- MVLAUMUQGRQERL-JTQLQIEISA-N levofloxacin n-oxide Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CC[N+](C)([O-])CC1 MVLAUMUQGRQERL-JTQLQIEISA-N 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 101000748141 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 32 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 102100040050 Ubiquitin carboxyl-terminal hydrolase 32 Human genes 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000000452 restraining effect Effects 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical group [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Description
Claims (3)
Priority Applications (1)
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CN201310118982.XA CN103172686B (zh) | 2013-04-08 | 2013-04-08 | 克拉霉素-n-氧化物的制备方法 |
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CN201310118982.XA CN103172686B (zh) | 2013-04-08 | 2013-04-08 | 克拉霉素-n-氧化物的制备方法 |
Publications (2)
Publication Number | Publication Date |
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CN103172686A true CN103172686A (zh) | 2013-06-26 |
CN103172686B CN103172686B (zh) | 2015-06-24 |
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CN201310118982.XA Expired - Fee Related CN103172686B (zh) | 2013-04-08 | 2013-04-08 | 克拉霉素-n-氧化物的制备方法 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106146577A (zh) * | 2015-03-25 | 2016-11-23 | 上海医药工业研究院 | 一种泰拉霉素有关物质、其制备方法及应用 |
CN110655544A (zh) * | 2018-06-28 | 2020-01-07 | 洛阳惠中兽药有限公司 | 一种加米霉素有关物质的分离、制备及纯化方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6809188B1 (en) * | 1999-11-24 | 2004-10-26 | Hanmi Pahrm. Co., Ltd. | Method of preparing clarithromycin |
CN101939327A (zh) * | 2008-02-08 | 2011-01-05 | 巴斯利尔药物股份公司 | 新的大环内酯类及其用途 |
-
2013
- 2013-04-08 CN CN201310118982.XA patent/CN103172686B/zh not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6809188B1 (en) * | 1999-11-24 | 2004-10-26 | Hanmi Pahrm. Co., Ltd. | Method of preparing clarithromycin |
CN101939327A (zh) * | 2008-02-08 | 2011-01-05 | 巴斯利尔药物股份公司 | 新的大环内酯类及其用途 |
Non-Patent Citations (1)
Title |
---|
EDWIN H. FLYNN,等: "Erythromycin.I.Properties and Degradation Studies", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》, vol. 76, 20 June 1954 (1954-06-20), pages 3121 - 3131 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106146577A (zh) * | 2015-03-25 | 2016-11-23 | 上海医药工业研究院 | 一种泰拉霉素有关物质、其制备方法及应用 |
CN106146577B (zh) * | 2015-03-25 | 2019-04-12 | 上海医药工业研究院 | 一种泰拉霉素有关物质、其制备方法及应用 |
CN110655544A (zh) * | 2018-06-28 | 2020-01-07 | 洛阳惠中兽药有限公司 | 一种加米霉素有关物质的分离、制备及纯化方法 |
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CN103172686B (zh) | 2015-06-24 |
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Owner name: SHANDONG UNIVERSITY Free format text: FORMER OWNER: SHANDONG INSTITUTE FOR FOOD AND DRUG CONTROL Effective date: 20150515 Owner name: SHANDONG INSTITUTE FOR FOOD AND DRUG CONTROL Effective date: 20150515 |
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CB03 | Change of inventor or designer information |
Inventor after: Wang Weijian Inventor after: Liu Fei Inventor after: Li Haifang Inventor after: Huang Ying Inventor after: Ran Xiaojing Inventor after: Li Jun Inventor after: Lou Hongxiang Inventor before: Wang Weijian Inventor before: Li Jun Inventor before: Li Haifang Inventor before: Xie Yuanchao Inventor before: Wang Bo Inventor before: Wang Kun Inventor before: Zhang Zhonghu |
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COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: WANG WEIJIAN LI JUN LI HAIFANG XIE YUANCHAO WANG BO WANG KUN ZHANG ZHONGHU TO: WANG WEIJIAN LIU FEI LI HAIFANG HUANG YING RAN XIAOJING LI JUN LOU HONGXIANG |
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TA01 | Transfer of patent application right |
Effective date of registration: 20150515 Address after: 250014 No. 27 South Grand Road, Shandong, Ji'nan Applicant after: Shandong University Applicant after: Food and medicine Inspection Research institute of Shandong Province Address before: Xinluo Avenue Ji'nan high tech Development Zone of Shandong Province, No. 2749 250101 Applicant before: Shandong Institute for Food and Drug Control |
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C14 | Grant of patent or utility model | ||
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CF01 | Termination of patent right due to non-payment of annual fee | ||
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Granted publication date: 20150624 Termination date: 20160408 |