CN103665068B - 一种1-N-乙基庆大霉素C1a的制备方法 - Google Patents
一种1-N-乙基庆大霉素C1a的制备方法 Download PDFInfo
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- CN103665068B CN103665068B CN201310691184.6A CN201310691184A CN103665068B CN 103665068 B CN103665068 B CN 103665068B CN 201310691184 A CN201310691184 A CN 201310691184A CN 103665068 B CN103665068 B CN 103665068B
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- temperature
- gentamicinc
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- trichloromethane
- ethyl
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- 238000000034 method Methods 0.000 title abstract description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229960001701 chloroform Drugs 0.000 claims abstract description 19
- 239000000243 solution Substances 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
- 238000010790 dilution Methods 0.000 claims abstract description 11
- 239000012895 dilution Substances 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 8
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 8
- 229960000583 acetic acid Drugs 0.000 claims abstract description 7
- 238000004108 freeze drying Methods 0.000 claims abstract description 7
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000470 constituent Substances 0.000 claims abstract description 6
- 238000000605 extraction Methods 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 6
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000013375 chromatographic separation Methods 0.000 claims description 5
- 238000011068 loading method Methods 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 2
- 238000004440 column chromatography Methods 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- 229950009953 etimicin Drugs 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 3
- OEBISAUVQBGQKC-ZIZSAZPJSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4-amino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](NC)[C@@](C)(O)CO1)O)NCC)[C@H]1O[C@H](CN)CC[C@H]1N OEBISAUVQBGQKC-ZIZSAZPJSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 2
- VEGXETMJINRLTH-ALRICIOSSA-N etimicin 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-ALRICIOSSA-N 0.000 description 2
- DNYGXMICFMACRA-UHFFFAOYSA-N gentamicin C1A Natural products O1C(CNC)CCC(N)C1OC1C(O)C(OC2C(C(NC)C(C)(O)CO2)O)C(N)CC1N DNYGXMICFMACRA-UHFFFAOYSA-N 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 241000589291 Acinetobacter Species 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- JFPVXVDWJQMJEE-QMTHXVAHSA-N Cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)C(=NOC)C1=CC=CO1 JFPVXVDWJQMJEE-QMTHXVAHSA-N 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 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 description 1
- DNYGXMICFMACRA-XHEDQWPISA-N Gentamicin C2b Chemical compound O1[C@H](CNC)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 DNYGXMICFMACRA-XHEDQWPISA-N 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 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 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 229960004744 micronomicin Drugs 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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CN108409814A (zh) * | 2018-03-07 | 2018-08-17 | 福安药业集团宁波天衡制药有限公司 | 一种硫酸依替米星的制备方法 |
CN113185561A (zh) * | 2021-04-24 | 2021-07-30 | 无锡济煜山禾药业股份有限公司 | 一种利用管道反应水解得到1-N-乙基庆大霉素C1a方法 |
Citations (4)
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 |
EP0546179B1 (en) * | 1990-08-24 | 1997-02-12 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | 4-o-(aminoglycosyl)- or 4,6-di-o-(aminoglycosyl)-2,5-dideoxy-5,5-difluorostreptamine derivative and production thereof |
CN101928311A (zh) * | 2010-03-26 | 2010-12-29 | 常州方圆制药有限公司 | 1-N-乙基庆大霉素C1a的制备方法 |
CN101928312A (zh) * | 2010-03-26 | 2010-12-29 | 常州方圆制药有限公司 | 1-N-乙基庆大霉素C1a硫酸盐的制备方法 |
-
2013
- 2013-12-16 CN CN201310691184.6A patent/CN103665068B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0546179B1 (en) * | 1990-08-24 | 1997-02-12 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | 4-o-(aminoglycosyl)- or 4,6-di-o-(aminoglycosyl)-2,5-dideoxy-5,5-difluorostreptamine derivative and production thereof |
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 |
CN101928311A (zh) * | 2010-03-26 | 2010-12-29 | 常州方圆制药有限公司 | 1-N-乙基庆大霉素C1a的制备方法 |
CN101928312A (zh) * | 2010-03-26 | 2010-12-29 | 常州方圆制药有限公司 | 1-N-乙基庆大霉素C1a硫酸盐的制备方法 |
Non-Patent Citations (1)
Title |
---|
Fluorinated o-Aminophenol Derivatives for Measurement of Intracellular pH;Chung K. Rhee,等;《Bioconjugafe Chem.》;19951231;第6卷(第1期);第78页方案1及第79页右栏第5段 * |
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Address after: 214028 Changjiang South Road, new Wu District, Wuxi, Jiangsu Province, No. 12 Co-patentee after: JIANGXI JEMINCARE GROUP Co.,Ltd. Patentee after: Wuxi Jiyu Shanhe Pharmaceutical Co.,Ltd. Address before: 214028 No. 12 Changjiang South Road, New District, Jiangsu, Wuxi Co-patentee before: JIANGXI JEMINCARE GROUP Co.,Ltd. Patentee before: WUXI JIMIN KEXIN SHANHE PHARMACEUTICAL Co.,Ltd. |
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Denomination of invention: A preparation method of 1-n-ethyl gentamicin C1A Effective date of registration: 20211223 Granted publication date: 20160113 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: JIANGXI JEMINCARE GROUP Co.,Ltd. Registration number: Y2021980016166 |
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Date of cancellation: 20220902 Granted publication date: 20160113 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: JIANGXI JEMINCARE GROUP Co.,Ltd. Registration number: Y2021980016166 |
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Denomination of invention: A kind of preparation method of 1-N-ethyl gentamicin C1a Effective date of registration: 20220905 Granted publication date: 20160113 Pledgee: Bank of China Limited Nanchang Qingyunpu sub branch Pledgor: JIANGXI JEMINCARE GROUP Co.,Ltd. Registration number: Y2022980014583 |
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