JPS58109496A - マクロライド抗生物質の合成の化学的方法 - Google Patents
マクロライド抗生物質の合成の化学的方法Info
- Publication number
- JPS58109496A JPS58109496A JP57208363A JP20836382A JPS58109496A JP S58109496 A JPS58109496 A JP S58109496A JP 57208363 A JP57208363 A JP 57208363A JP 20836382 A JP20836382 A JP 20836382A JP S58109496 A JPS58109496 A JP S58109496A
- Authority
- JP
- Japan
- Prior art keywords
- fluoroerythromycin
- carried out
- oxide
- hydrogen
- compound
- 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
- 239000003120 macrolide antibiotic agent Substances 0.000 title description 4
- 238000003786 synthesis reaction Methods 0.000 title description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 39
- 229960001398 flurithromycin Drugs 0.000 claims description 38
- XOEUHCONYHZURQ-HNUBZJOYSA-N flurithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@@](C)(F)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 XOEUHCONYHZURQ-HNUBZJOYSA-N 0.000 claims description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 19
- 150000001204 N-oxides Chemical class 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- 238000003682 fluorination reaction Methods 0.000 claims description 9
- XHFXMNZYIKFCPN-UHFFFAOYSA-N perchloryl fluoride Chemical compound FCl(=O)(=O)=O XHFXMNZYIKFCPN-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 claims description 4
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000292 calcium oxide Substances 0.000 claims description 3
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 239000000052 vinegar Substances 0.000 claims description 3
- 235000021419 vinegar Nutrition 0.000 claims description 3
- WNNZXPCARMJAOB-UHFFFAOYSA-N acetic acid hydrofluoride Chemical compound F.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O WNNZXPCARMJAOB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 230000011987 methylation Effects 0.000 claims description 2
- 238000007069 methylation reaction Methods 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 239000012022 methylating agents Substances 0.000 claims 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000003610 charcoal Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 229940029284 trichlorofluoromethane Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 24
- 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 19
- 239000012043 crude product Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 241000187747 Streptomyces Species 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229960003276 erythromycin Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000007429 general method Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000000855 fermentation Methods 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 230000000704 physical effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000004810 partition chromatography Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229930006677 Erythromycin A Natural products 0.000 description 4
- MWFRKHPRXPSWNT-UHFFFAOYSA-N Erythromycin-C Natural products CC1C(OC2C(C(CC(C)O2)N(C)C)O)C(C)(O)CC(C)C(=O)C(C)C(O)C(O)(C)C(CC)OC(=O)C(C)C1OC1CC(C)(O)C(O)C(C)O1 MWFRKHPRXPSWNT-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000010520 demethylation reaction Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000006485 reductive methylation reaction Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- CLQUUOKNEOQBSW-KEGKUKQHSA-N erythromycin D Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@H]([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)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 CLQUUOKNEOQBSW-KEGKUKQHSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012025 fluorinating agent Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 229910001916 chloryl Inorganic materials 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- -1 fluorooxy Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- DGQBNDRZRZYTER-UHFFFAOYSA-N (pentafluoro-$l^{6}-sulfanyl) hypofluorite Chemical compound FOS(F)(F)(F)(F)F DGQBNDRZRZYTER-UHFFFAOYSA-N 0.000 description 1
- CDPJAUXESYIAMG-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethyl hypofluorite Chemical compound FOC(F)(F)C(F)(F)F CDPJAUXESYIAMG-UHFFFAOYSA-N 0.000 description 1
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- 108010039224 Amidophosphoribosyltransferase Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZOYWWAGVGBSJDL-UHFFFAOYSA-N D-desosamine Natural products CC1CC(N(C)C)C(O)C(O)O1 ZOYWWAGVGBSJDL-UHFFFAOYSA-N 0.000 description 1
- 241000257465 Echinoidea Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000600169 Maro Species 0.000 description 1
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241001474791 Proboscis Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- XCSXAUBKYZLNAM-UHFFFAOYSA-N [O].C(F)(F)F Chemical compound [O].C(F)(F)F XCSXAUBKYZLNAM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000012255 calcium oxide Nutrition 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012926 crystallographic analysis Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- VTJCSBJRQLZNHE-CSMHCCOUSA-N desosamine Chemical group C[C@@H](O)C[C@H](N(C)C)[C@@H](O)C=O VTJCSBJRQLZNHE-CSMHCCOUSA-N 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229930193775 erythronolide Natural products 0.000 description 1
- YVTFLQUPRIIRFE-QUMKBVJLSA-N erythronolide A Chemical compound CC[C@H]1OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O YVTFLQUPRIIRFE-QUMKBVJLSA-N 0.000 description 1
- ZFBRGCCVTUPRFQ-UHFFFAOYSA-N erythronolide-B Natural products CCC1OC(=O)C(C)C(O)C(C)C(O)C(C)(O)CC(C)C(=O)C(C)C(O)C1C ZFBRGCCVTUPRFQ-UHFFFAOYSA-N 0.000 description 1
- 230000012173 estrus Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000002373 hemiacetals Chemical class 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940116736 romycin Drugs 0.000 description 1
- 210000004894 snout Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT25345A/81 | 1981-11-27 | ||
| IT25345/81A IT1195299B (it) | 1981-11-27 | 1981-11-27 | Procedimento chimico di sintesi per la preparazione di antibiotici macrolidici |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58109496A true JPS58109496A (ja) | 1983-06-29 |
| JPH0312077B2 JPH0312077B2 (en, 2012) | 1991-02-19 |
Family
ID=11216419
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57208363A Granted JPS58109496A (ja) | 1981-11-27 | 1982-11-27 | マクロライド抗生物質の合成の化学的方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4514562A (en, 2012) |
| EP (1) | EP0080763B1 (en, 2012) |
| JP (1) | JPS58109496A (en, 2012) |
| KR (1) | KR880001566B1 (en, 2012) |
| AT (1) | ATE15805T1 (en, 2012) |
| BE (1) | BE895155A (en, 2012) |
| CA (1) | CA1209987A (en, 2012) |
| CH (1) | CH660596A5 (en, 2012) |
| DE (1) | DE3266578D1 (en, 2012) |
| FI (1) | FI75835C (en, 2012) |
| FR (1) | FR2517311B1 (en, 2012) |
| IT (1) | IT1195299B (en, 2012) |
| PH (1) | PH18391A (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6038394A (ja) * | 1983-07-18 | 1985-02-27 | ピエレル・ソチエタ・ペル・アチオニ | （８ｓ）‐８‐フルオルエリスロマイシンの合成法 |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1196041B (it) * | 1984-03-08 | 1988-11-10 | Pierrel Spa | Emichetali di (8s)-8-fluoroeritromicine,il procedimento per la loro preparazione e le formulazioni adatte alla somministrazione orale che contengono i prodotti |
| DE3424525A1 (de) * | 1984-07-04 | 1986-01-16 | Kernforschungsanlage Jülich GmbH, 5170 Jülich | Verfahren zur herstellung von (pfeil hoch)1(pfeil hoch)(pfeil hoch)8(pfeil hoch)f-alkyl- und arylverbindungen durch halogenaustausch |
| JPS6185378A (ja) * | 1984-10-02 | 1986-04-30 | Daikin Ind Ltd | ８−フルオロエリスロノライド誘導体の製法 |
| US4876245A (en) * | 1986-12-22 | 1989-10-24 | Daikin Industries Ltd. | Fluorine-containing macrolide compounds and their use |
| MA21697A1 (fr) * | 1988-12-19 | 1990-07-01 | Dow Agrosciences Llc | Composes de macrolides. |
| US5591606A (en) * | 1992-11-06 | 1997-01-07 | Dowelanco | Process for the production of A83543 compounds with Saccharopolyspora spinosa |
| JP4258575B2 (ja) * | 1993-03-12 | 2009-04-30 | ダウ・アグロサイエンス・エル・エル・シー | 新規ａ８３５４３化合物及びそれらの製造法 |
| US5393743A (en) * | 1993-07-06 | 1995-02-28 | Abbott Laboratories | Erythromycin derivatives |
| US5552533A (en) * | 1994-09-14 | 1996-09-03 | Alliedsignal Inc. | Preparation of (8S)-8-fluoroerythromycins with N-F fluorinating agents |
| US6001981A (en) * | 1996-06-13 | 1999-12-14 | Dow Agrosciences Llc | Synthetic modification of Spinosyn compounds |
| WO2005082996A1 (fr) * | 2004-02-24 | 2005-09-09 | Arkema France | Composition reticulee comprenant un copolymere sequence triblocs, son procede d'obtention et ses utilisations |
| WO2011080739A2 (en) | 2009-12-29 | 2011-07-07 | Yeda Research And Development Co. Ltd. | Synergistic antibiotic combinations and derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2812323A (en) * | 1954-11-03 | 1957-11-05 | Lilly Co Eli | Des-n-methyl erythromycin |
| US3674773A (en) * | 1970-10-06 | 1972-07-04 | Abbott Lab | Erythromycin derivatives |
| FI72346C (fi) * | 1981-01-09 | 1987-05-11 | Pierrel Spa | Saett att framstaella nya halvsyntetiska makrolidantibiotika. |
-
1981
- 1981-11-27 IT IT25345/81A patent/IT1195299B/it active
-
1982
- 1982-11-19 EP EP82201476A patent/EP0080763B1/en not_active Expired
- 1982-11-19 DE DE8282201476T patent/DE3266578D1/de not_active Expired
- 1982-11-19 AT AT82201476T patent/ATE15805T1/de not_active IP Right Cessation
- 1982-11-22 US US06/443,580 patent/US4514562A/en not_active Expired - Lifetime
- 1982-11-26 FI FI824084A patent/FI75835C/fi not_active IP Right Cessation
- 1982-11-26 KR KR8205343A patent/KR880001566B1/ko not_active Expired
- 1982-11-26 FR FR8219865A patent/FR2517311B1/fr not_active Expired
- 1982-11-26 CH CH6889/82A patent/CH660596A5/it not_active IP Right Cessation
- 1982-11-26 BE BE0/209580A patent/BE895155A/fr unknown
- 1982-11-26 PH PH28203A patent/PH18391A/en unknown
- 1982-11-26 CA CA000416447A patent/CA1209987A/en not_active Expired
- 1982-11-27 JP JP57208363A patent/JPS58109496A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6038394A (ja) * | 1983-07-18 | 1985-02-27 | ピエレル・ソチエタ・ペル・アチオニ | （８ｓ）‐８‐フルオルエリスロマイシンの合成法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CH660596A5 (it) | 1987-05-15 |
| US4514562A (en) | 1985-04-30 |
| CA1209987A (en) | 1986-08-19 |
| DE3266578D1 (en) | 1985-10-31 |
| FR2517311B1 (fr) | 1987-12-24 |
| FI75835C (fi) | 1988-08-08 |
| FR2517311A1 (fr) | 1983-06-03 |
| KR840002413A (ko) | 1984-07-02 |
| BE895155A (fr) | 1983-03-16 |
| EP0080763A1 (en) | 1983-06-08 |
| FI75835B (fi) | 1988-04-29 |
| KR880001566B1 (ko) | 1988-08-22 |
| ATE15805T1 (de) | 1985-10-15 |
| PH18391A (en) | 1985-06-21 |
| EP0080763B1 (en) | 1985-09-25 |
| JPH0312077B2 (en, 2012) | 1991-02-19 |
| IT1195299B (it) | 1988-10-12 |
| IT8125345A0 (it) | 1981-11-27 |
| FI824084L (fi) | 1983-05-28 |
| FI824084A0 (fi) | 1982-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK172636B1 (en) | 6-o-methylerythromycin a derivative | |
| CA1239639A (en) | Epimeric azahomoerythromycin a derivative and intermediates therefor | |
| JPS58109496A (ja) | マクロライド抗生物質の合成の化学的方法 | |
| JP3083102B2 (ja) | エリスロマイシンおよびアジスロマイシンの３”−デスメトキシ誘導体 | |
| JPS6364438B2 (en, 2012) | ||
| PL195910B1 (pl) | Sposób wytwarzania 9-deokso-9a-aza-9a-metylo-9a-homoerytromycyny A w formie niekrystalicznej | |
| JPH07501317A (ja) | モルフィン−６−グルクロナイドあるいは置換モルフィン−６−グルクロナイドの製法 | |
| US4496717A (en) | Erythromycin B derivatives | |
| JPS58159499A (ja) | 抗菌剤として有用な４″−エピエリスロマイシンａおよびその誘導体 | |
| EP0080819B1 (en) | 11-0-alkylerythromycin a derivatives | |
| TANAKA et al. | Synthesis of 6-aroyluridine from uridine via regiospecific lithiation | |
| US6140479A (en) | Erythromycin a derivatives | |
| JPH0570474A (ja) | ９−デオキソ−９（ｚ）−ヒドロキシイミノエリスロマイシンａおよびそのｏ−誘導体 | |
| EP0081305B1 (en) | Erythromycin a derivatives | |
| JP6173427B2 (ja) | α−ハロテトラアシルグルコースの製造方法 | |
| JPS63287793A (ja) | 新規マクロライド誘導体、その製法および該誘導体を含有する薬用組成物 | |
| US5043324A (en) | Macrolide compounds | |
| US5032581A (en) | Tylosin derivatives | |
| EP0508725A1 (en) | Novel process for the preparation of 8a-aza-8a-homoerythromycin cyclic iminoethers | |
| US20060019908A1 (en) | Process for the preparation of azithromycin monohydrate isopropanol clathrate | |
| SE445223B (sv) | Sett att framstella 4"-amino-erytomylin-a-derivat | |
| JPS632274B2 (en, 2012) | ||
| CA1213278A (en) | 3-azinomethyl rifamycins | |
| JPS6152839B2 (en, 2012) | ||
| EP0508795A1 (en) | 8a-aza-8a-homoerythromycin cyclic iminoethers |