TWI801438B - 抗菌胺基糖苷類似物之合成 - Google Patents
抗菌胺基糖苷類似物之合成 Download PDFInfo
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- TWI801438B TWI801438B TW107136676A TW107136676A TWI801438B TW I801438 B TWI801438 B TW I801438B TW 107136676 A TW107136676 A TW 107136676A TW 107136676 A TW107136676 A TW 107136676A TW I801438 B TWI801438 B TW I801438B
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- 230000015572 biosynthetic process Effects 0.000 title claims description 41
- 229940126575 aminoglycoside Drugs 0.000 title abstract description 9
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 5
- 238000003786 synthesis reaction Methods 0.000 title description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 422
- 238000000034 method Methods 0.000 claims abstract description 264
- 239000013078 crystal Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims description 283
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 280
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 213
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- 239000000203 mixture Substances 0.000 claims description 167
- -1 (4-nitro Benzyl)oxy Chemical group 0.000 claims description 152
- 239000011541 reaction mixture Substances 0.000 claims description 124
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- 229940011051 isopropyl acetate Drugs 0.000 claims description 99
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 95
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 81
- 239000003153 chemical reaction reagent Substances 0.000 claims description 70
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- 230000008569 process Effects 0.000 claims description 42
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- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 35
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 25
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 20
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 16
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- 239000012351 deprotecting agent Substances 0.000 claims description 14
- MKIHFLQNZUDOQW-UHFFFAOYSA-N (4-nitrophenyl)methyl benzotriazole-1-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)N1C2=CC=CC=C2N=N1 MKIHFLQNZUDOQW-UHFFFAOYSA-N 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 6
- IYDYFVUFSPQPPV-PEXOCOHZSA-N (2s)-4-amino-n-[(1r,2s,3s,4r,5s)-5-amino-4-[[(2s,3r)-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2h-pyran-2-yl]oxy]-2-[(2r,3r,4r,5r)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide 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(CNCCO)O2)N)[C@@H](N)C[C@H]1NC(=O)[C@@H](O)CCN IYDYFVUFSPQPPV-PEXOCOHZSA-N 0.000 claims description 4
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- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims 1
- JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 claims 1
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- 238000002425 crystallisation Methods 0.000 description 51
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- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 29
- 239000008346 aqueous phase Substances 0.000 description 29
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- 229910021641 deionized water Inorganic materials 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
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- 239000012535 impurity Substances 0.000 description 21
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 20
- 229960005456 sisomicin Drugs 0.000 description 20
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 19
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
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- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical group C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
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- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
- C07H15/236—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2 a saccharide radical being substituted by an alkylamino radical in position 3 and by two substituents different from hydrogen in position 4, e.g. gentamicin complex, sisomicin, verdamycin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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- Y02P20/50—Improvements relating to the production of bulk chemicals
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| CN110878108B (zh) * | 2019-06-17 | 2022-11-11 | 山东安信制药有限公司 | 一种普拉佐米星的合成方法 |
| CN110885350A (zh) * | 2019-08-28 | 2020-03-17 | 山东安信制药有限公司 | 一种普拉佐米星的制备方法 |
| CN110642907B (zh) * | 2019-10-12 | 2020-11-06 | 上海博璞诺科技发展有限公司 | 普拉唑米星或其盐的合成方法 |
| CN111116688B (zh) * | 2020-01-07 | 2021-07-27 | 杭州华东医药集团新药研究院有限公司 | 普拉佐米星的制备方法 |
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| TW201000467A (en) * | 2008-03-17 | 2010-01-01 | Aeterna Zentaris Gmbh | Novel 1,2,4-triazole derivatives and process of manufacturing thereof |
| WO2010132770A1 (en) * | 2009-05-14 | 2010-11-18 | Achaogen, Inc. | Treatment of klebsiella pneumoniae infections with antibacterial aminoglycoside compounds |
| WO2010132777A2 (en) * | 2009-05-14 | 2010-11-18 | Achaogen, Inc. | Treatment of urinary tract infections with antibacterial aminoglycoside compounds |
| WO2010147836A1 (en) * | 2009-06-17 | 2010-12-23 | Achaogen, Inc. | Combination therapies using antibacterial aminoglycoside compounds |
| WO2011143497A1 (en) * | 2010-05-12 | 2011-11-17 | Rempex Pharmaceuticals, Inc. | Aminoglycoside derivatives |
| WO2014145713A2 (en) * | 2013-03-15 | 2014-09-18 | The Board Of Trustees Of The Leland Stanford Junior University | Aminoglycoside antibiotics with reduced ototoxicity |
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| US4388233A (en) * | 1981-05-15 | 1983-06-14 | The Regents Of The University Of California | Synthetic substrates for enzyme analysis |
| MX2009003909A (es) | 2006-10-12 | 2009-05-25 | Ptc Therapeutics Inc | Métodos para dosificar un compuesto 1,2,4, - oxadiazol oralmente activo para el tratamiento de supresión de la mutación finalizadora. |
| US8614233B2 (en) * | 2007-05-29 | 2013-12-24 | Universite De Montreal | Cinnamoyl inhibitors of transglutaminase |
| LT2217610T (lt) | 2007-11-21 | 2017-02-27 | Achaogen, Inc. | Antibakteriniai aminoglikozidų analogai |
| WO2019079613A1 (en) * | 2017-10-19 | 2019-04-25 | Achaogen, Inc. | SYNTHESIS OF ANTIBACTERIAL AMINOGLYCOSIDE ANALOGUES |
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- 2023-08-22 AU AU2023219819A patent/AU2023219819B2/en active Active
-
2024
- 2024-09-20 US US18/892,191 patent/US20250122177A1/en active Pending
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2025
- 2025-01-31 JP JP2025015211A patent/JP2025062009A/ja active Pending
- 2025-09-05 AU AU2025226793A patent/AU2025226793A1/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201000467A (en) * | 2008-03-17 | 2010-01-01 | Aeterna Zentaris Gmbh | Novel 1,2,4-triazole derivatives and process of manufacturing thereof |
| WO2010132770A1 (en) * | 2009-05-14 | 2010-11-18 | Achaogen, Inc. | Treatment of klebsiella pneumoniae infections with antibacterial aminoglycoside compounds |
| WO2010132777A2 (en) * | 2009-05-14 | 2010-11-18 | Achaogen, Inc. | Treatment of urinary tract infections with antibacterial aminoglycoside compounds |
| WO2010147836A1 (en) * | 2009-06-17 | 2010-12-23 | Achaogen, Inc. | Combination therapies using antibacterial aminoglycoside compounds |
| WO2011143497A1 (en) * | 2010-05-12 | 2011-11-17 | Rempex Pharmaceuticals, Inc. | Aminoglycoside derivatives |
| WO2014145713A2 (en) * | 2013-03-15 | 2014-09-18 | The Board Of Trustees Of The Leland Stanford Junior University | Aminoglycoside antibiotics with reduced ototoxicity |
Also Published As
| Publication number | Publication date |
|---|---|
| AR113780A1 (es) | 2020-06-10 |
| CN111655709A (zh) | 2020-09-11 |
| US12122769B2 (en) | 2024-10-22 |
| US20250122177A1 (en) | 2025-04-17 |
| US20230074115A1 (en) | 2023-03-09 |
| AU2018353156A1 (en) | 2020-05-07 |
| EP3697797A1 (en) | 2020-08-26 |
| JP2025062009A (ja) | 2025-04-11 |
| MX2020003701A (es) | 2020-07-22 |
| EA202090980A1 (ru) | 2020-10-07 |
| CN111655709B (zh) | 2024-01-02 |
| JP2021500354A (ja) | 2021-01-07 |
| WO2019079613A1 (en) | 2019-04-25 |
| CA3079508A1 (en) | 2019-04-25 |
| US20200317652A1 (en) | 2020-10-08 |
| RU2020116171A (ru) | 2021-11-19 |
| AU2023219819A1 (en) | 2023-09-07 |
| BR112020007740A2 (pt) | 2020-10-13 |
| AU2025226793A1 (en) | 2025-09-25 |
| JP2023054316A (ja) | 2023-04-13 |
| JP7235741B2 (ja) | 2023-03-08 |
| US11453658B2 (en) | 2022-09-27 |
| TW201922233A (zh) | 2019-06-16 |
| RU2020116171A3 (https=) | 2022-03-03 |
| AU2023219819B2 (en) | 2025-06-05 |
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