CY1241A - Process for the preparation of kanamycin derivatives - Google Patents
Process for the preparation of kanamycin derivatives Download PDFInfo
- Publication number
- CY1241A CY1241A CY1241A CY124178A CY1241A CY 1241 A CY1241 A CY 1241A CY 1241 A CY1241 A CY 1241A CY 124178 A CY124178 A CY 124178A CY 1241 A CY1241 A CY 1241A
- Authority
- CY
- Cyprus
- Prior art keywords
- kanamycin
- acid
- amino
- polysilylated
- moles
- Prior art date
Links
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical class O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 title claims description 166
- 238000002360 preparation method Methods 0.000 title claims description 50
- 238000000034 method Methods 0.000 title claims description 45
- 229960000318 kanamycin Drugs 0.000 claims description 158
- 229930182823 kanamycin A Natural products 0.000 claims description 158
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 81
- 229960004821 amikacin Drugs 0.000 claims description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 71
- 239000000203 mixture Substances 0.000 claims description 70
- 229910001868 water Inorganic materials 0.000 claims description 69
- SKKLOUVUUNMCJE-FQSMHNGLSA-N kanamycin B Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SKKLOUVUUNMCJE-FQSMHNGLSA-N 0.000 claims description 53
- 229960001192 bekanamycin Drugs 0.000 claims description 52
- -1 N-hydroxy-5-norbornene-2,3-dicarboximide ester Chemical class 0.000 claims description 51
- 229930182824 kanamycin B Natural products 0.000 claims description 51
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 48
- 239000002253 acid Substances 0.000 claims description 41
- 230000000903 blocking effect Effects 0.000 claims description 41
- 239000007787 solid Substances 0.000 claims description 30
- 239000000047 product Substances 0.000 claims description 27
- 239000000706 filtrate Substances 0.000 claims description 24
- 238000005406 washing Methods 0.000 claims description 23
- 239000007858 starting material Substances 0.000 claims description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 19
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 19
- 229930027917 kanamycin Natural products 0.000 claims description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 15
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 14
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 13
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 150000008065 acid anhydrides Chemical class 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 231100000252 nontoxic Toxicity 0.000 claims description 9
- 230000003000 nontoxic effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- QRAFJHXNLQTXQW-UHFFFAOYSA-N 2-methylpropyl hydrogen carbonate Chemical compound CC(C)COC(O)=O QRAFJHXNLQTXQW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 5
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- NJAPCAIWQRPQPY-UHFFFAOYSA-N benzyl hydrogen carbonate Chemical compound OC(=O)OCC1=CC=CC=C1 NJAPCAIWQRPQPY-UHFFFAOYSA-N 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000005544 phthalimido group Chemical group 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 214
- 241001558496 Talpa caeca Species 0.000 description 87
- 239000000243 solution Substances 0.000 description 82
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 74
- 238000005917 acylation reaction Methods 0.000 description 64
- 230000010933 acylation Effects 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000003756 stirring Methods 0.000 description 31
- 239000003054 catalyst Substances 0.000 description 29
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- 239000000463 material Substances 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 238000006884 silylation reaction Methods 0.000 description 20
- SWOHHBNJQHDNFM-WYSMZKEGSA-N (2s)-4-amino-n-[(1s,2r,3r,4s,5r)-5-amino-4-[(2s,3r,4s,5s,6r)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3r,4s,5s,6r)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide;sulfuric acid Chemical compound OS(O)(=O)=O.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](O)[C@H](O)[C@@H](CN)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O SWOHHBNJQHDNFM-WYSMZKEGSA-N 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 15
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 13
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 13
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 11
- 230000002906 microbiologic effect Effects 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 239000012141 concentrate Substances 0.000 description 10
- 235000008504 concentrate Nutrition 0.000 description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 9
- 240000000220 Panda oleosa Species 0.000 description 8
- 235000016496 Panda oleosa Nutrition 0.000 description 8
- 239000000908 ammonium hydroxide Substances 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 238000013019 agitation Methods 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 238000010926 purge Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QPEJHSFTZVMSJH-UHFFFAOYSA-N 3-amino-5-hydroxybenzoic acid Chemical compound NC1=CC(O)=CC(C(O)=O)=C1 QPEJHSFTZVMSJH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000010268 HPLC based assay Methods 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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- 239000005909 Kieselgur Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
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- 238000001035 drying Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 3
- LWFWUJCJKPUZLV-UHFFFAOYSA-N n-trimethylsilylacetamide Chemical compound CC(=O)N[Si](C)(C)C LWFWUJCJKPUZLV-UHFFFAOYSA-N 0.000 description 3
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- MASDFXZJIDNRTR-UHFFFAOYSA-N 1,3-bis(trimethylsilyl)urea Chemical compound C[Si](C)(C)NC(=O)N[Si](C)(C)C MASDFXZJIDNRTR-UHFFFAOYSA-N 0.000 description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 2
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- 206010019233 Headaches Diseases 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 230000006181 N-acylation Effects 0.000 description 2
- 208000010513 Stupor Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
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- 239000012736 aqueous medium Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
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- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical compound OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 description 2
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- 239000002808 molecular sieve Substances 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
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- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 239000005051 trimethylchlorosilane Substances 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
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- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- SBUJHOSQTJFQJX-FEPCMYDKSA-N kanamycin Polymers O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](OC2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-FEPCMYDKSA-N 0.000 description 1
- 229960000768 kanamycin a sulfate Drugs 0.000 description 1
- 229960002064 kanamycin sulfate Drugs 0.000 description 1
- 150000003932 ketenimines Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 201000003102 mental depression Diseases 0.000 description 1
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- 239000005055 methyl trichlorosilane Substances 0.000 description 1
- JLUFWMXJHAVVNN-UHFFFAOYSA-N methyltrichlorosilane Chemical compound C[Si](Cl)(Cl)Cl JLUFWMXJHAVVNN-UHFFFAOYSA-N 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- LMSCAPYDLTUYDG-UHFFFAOYSA-N n-triethylsilylethanamine Chemical compound CCN[Si](CC)(CC)CC LMSCAPYDLTUYDG-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
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- 239000012074 organic phase Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical class [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ZOYFEXPFPVDYIS-UHFFFAOYSA-N trichloro(ethyl)silane Chemical compound CC[Si](Cl)(Cl)Cl ZOYFEXPFPVDYIS-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000010930 yellow gold Substances 0.000 description 1
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Classifications
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79180677A | 1977-04-28 | 1977-04-28 | |
| US88858578A | 1978-03-20 | 1978-03-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1241A true CY1241A (en) | 1984-06-29 |
Family
ID=27121201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY1241A CY1241A (en) | 1977-04-28 | 1978-04-26 | Process for the preparation of kanamycin derivatives |
Country Status (27)
| Country | Link |
|---|---|
| JP (1) | JPS53149951A (OSRAM) |
| AR (1) | AR218910A1 (OSRAM) |
| AT (1) | AT357675B (OSRAM) |
| CA (2) | CA1100953A (OSRAM) |
| CH (1) | CH639104A5 (OSRAM) |
| CS (1) | CS207607B2 (OSRAM) |
| CY (1) | CY1241A (OSRAM) |
| DE (2) | DE2818822A1 (OSRAM) |
| DK (2) | DK172543B1 (OSRAM) |
| EG (1) | EG13710A (OSRAM) |
| ES (1) | ES469303A1 (OSRAM) |
| FI (1) | FI781288A7 (OSRAM) |
| FR (2) | FR2388827A1 (OSRAM) |
| GB (1) | GB1598294A (OSRAM) |
| HK (1) | HK51484A (OSRAM) |
| IE (2) | IE46945B1 (OSRAM) |
| IT (2) | IT1156718B (OSRAM) |
| KE (1) | KE3398A (OSRAM) |
| LU (1) | LU79541A1 (OSRAM) |
| MY (1) | MY8500528A (OSRAM) |
| NL (1) | NL178790C (OSRAM) |
| NO (2) | NO149635C (OSRAM) |
| PL (1) | PL117307B1 (OSRAM) |
| PT (1) | PT67959B (OSRAM) |
| SE (2) | SE447259B (OSRAM) |
| SG (1) | SG22884G (OSRAM) |
| YU (2) | YU102578A (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55306A (en) * | 1978-04-28 | 1980-01-05 | Bristol Myers Co | Manufacture of 11nn*omegaaaminooalphaahydroxy alkanoyl**aminoglycoside antibiotic |
| RU2004127917A (ru) * | 2002-02-19 | 2006-01-27 | Аматофармасьютикал Продактс, Лтд. (Jp) | Производное молочной кислоты |
| MX2010005632A (es) | 2007-11-21 | 2010-09-10 | Achaogen Inc | Analogos de aminoglucosidos antibacterianos. |
| WO2010132759A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of dibekacin |
| WO2010132768A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of sisomicin |
| WO2010132760A1 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial derivatives of tobramycin |
| WO2010132765A2 (en) | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial aminoglycoside analogs |
| WO2010132757A2 (en) * | 2009-05-15 | 2010-11-18 | Achaogen, Inc. | Antibacterial aminoglycoside analogs |
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1978
- 1978-04-21 AR AR271852A patent/AR218910A1/es active
- 1978-04-25 CA CA301,962A patent/CA1100953A/en not_active Expired
- 1978-04-25 FI FI781288A patent/FI781288A7/fi not_active Application Discontinuation
- 1978-04-25 CA CA301,968A patent/CA1105454A/en not_active Expired
- 1978-04-25 NO NO781437A patent/NO149635C/no unknown
- 1978-04-26 GB GB16571/78A patent/GB1598294A/en not_active Expired
- 1978-04-26 CY CY1241A patent/CY1241A/en unknown
- 1978-04-26 NL NLAANVRAGE7804503,A patent/NL178790C/xx not_active IP Right Cessation
- 1978-04-26 DK DK197801830A patent/DK172543B1/da not_active IP Right Cessation
- 1978-04-26 DK DK182978A patent/DK165450C/da not_active IP Right Cessation
- 1978-04-27 FR FR7812591A patent/FR2388827A1/fr active Granted
- 1978-04-27 CS CS782729A patent/CS207607B2/cs unknown
- 1978-04-27 IE IE841/78A patent/IE46945B1/en not_active IP Right Cessation
- 1978-04-27 YU YU01025/78A patent/YU102578A/xx unknown
- 1978-04-27 IE IE842/78A patent/IE47271B1/en not_active IP Right Cessation
- 1978-04-27 YU YU1024/78A patent/YU41590B/xx unknown
- 1978-04-27 LU LU79541A patent/LU79541A1/xx unknown
- 1978-04-27 FR FR7812589A patent/FR2388826A1/fr active Granted
- 1978-04-27 PT PT67959A patent/PT67959B/pt unknown
- 1978-04-28 AT AT312778A patent/AT357675B/de not_active IP Right Cessation
- 1978-04-28 SE SE7804973A patent/SE447259B/sv not_active IP Right Cessation
- 1978-04-28 CH CH470278A patent/CH639104A5/de not_active IP Right Cessation
- 1978-04-28 JP JP5016078A patent/JPS53149951A/ja active Granted
- 1978-04-28 DE DE19782818822 patent/DE2818822A1/de active Granted
- 1978-04-28 ES ES469303A patent/ES469303A1/es not_active Expired
- 1978-04-28 PL PL1978206457A patent/PL117307B1/pl unknown
- 1978-04-28 DE DE19782818992 patent/DE2818992A1/de active Granted
- 1978-04-28 IT IT49136/78A patent/IT1156718B/it active
- 1978-04-28 IT IT49137/78A patent/IT1105500B/it active
- 1978-04-29 EG EG283/78A patent/EG13710A/xx active
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1983
- 1983-04-05 NO NO83831197A patent/NO154697C/no unknown
- 1983-10-07 SE SE8305538A patent/SE461148B/sv not_active IP Right Cessation
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1984
- 1984-03-12 SG SG228/84A patent/SG22884G/en unknown
- 1984-04-12 KE KE3398A patent/KE3398A/xx unknown
- 1984-06-22 HK HK514/84A patent/HK51484A/en not_active IP Right Cessation
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1985
- 1985-12-30 MY MY528/85A patent/MY8500528A/xx unknown
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