CA1133475A - Antibiotiques macrolide 3"-acyles - Google Patents

Antibiotiques macrolide 3"-acyles

Info

Publication number: CA1133475A
Authority: CA; Canada
Prior art keywords: group; compound; formula; methanol; alkanoyl group
Prior art date: 1978-05-10
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.): Expired

Application number

CA327,269A

Other languages

English (en)

Inventor

Hideo Sakakibara

Tetsuo Matsuda

Susumu Watanabe

Tatsuro Fujiwara

Toshiyuki Watanabe

Osamu Okegawa

Satoshi Omura

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Toyo Jozo KK

Original Assignee

Toyo Jozo KK

Priority date (The priority date 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 date listed.)

1978-05-10

Filing date

1979-05-09

Publication date

1982-10-12

1979-05-09 Application filed by Toyo Jozo KK filed Critical Toyo Jozo KK

1982-10-12 Application granted granted Critical

1982-10-12 Publication of CA1133475A publication Critical patent/CA1133475A/fr

Status Expired legal-status Critical Current

Links

239000003120 macrolide antibiotic agent Substances 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 169
125000002252 acyl group Chemical group 0.000 claims abstract description 112
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
150000003839 salts Chemical class 0.000 claims abstract description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 252
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 105
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 78
238000000034 method Methods 0.000 claims description 57
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
238000010438 heat treatment Methods 0.000 claims description 53
229910021529 ammonia Inorganic materials 0.000 claims description 49
239000000203 mixture Substances 0.000 claims description 48
-1 carboxylic acid halide Chemical class 0.000 claims description 45
125000006239 protecting group Chemical group 0.000 claims description 40
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 32
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 24
239000003960 organic solvent Substances 0.000 claims description 22
239000000126 substance Substances 0.000 claims description 22
150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 12
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 10
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims description 9
150000007529 inorganic bases Chemical class 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
239000011260 aqueous acid Substances 0.000 claims description 5
125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 5
229910052736 halogen Inorganic materials 0.000 claims 4
229910052739 hydrogen Inorganic materials 0.000 claims 4
239000001257 hydrogen Substances 0.000 claims 4
125000005843 halogen group Chemical group 0.000 claims 3
125000001589 carboacyl group Chemical group 0.000 claims 1
150000002367 halogens Chemical class 0.000 claims 1
239000003242 anti bacterial agent Substances 0.000 abstract description 14
229940088710 antibiotic agent Drugs 0.000 abstract description 13
230000000844 anti-bacterial effect Effects 0.000 abstract description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 84
239000011541 reaction mixture Substances 0.000 description 66
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 60
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
239000000741 silica gel Substances 0.000 description 48
229910002027 silica gel Inorganic materials 0.000 description 48
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 47
229960001701 chloroform Drugs 0.000 description 42
JZVYPSLDMXOITF-UHFFFAOYSA-N Leucomycin A5 Natural products C1C(O)(C)C(OC(=O)CCC)C(C)OC1OC1C(N(C)C)C(O)C(OC2C(C(O)CC(=O)OC(C)CC=CC=CC(O)C(C)CC2CC=O)OC)OC1C JZVYPSLDMXOITF-UHFFFAOYSA-N 0.000 description 41
TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 36
125000002887 hydroxy group Chemical group [H]O* 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 31
239000000047 product Substances 0.000 description 31
239000000243 solution Substances 0.000 description 29
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
230000003115 biocidal effect Effects 0.000 description 23
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 23
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
238000001816 cooling Methods 0.000 description 21
239000000843 powder Substances 0.000 description 20
JZVYPSLDMXOITF-MJRCUCNNSA-N Leucomycin A5 Chemical compound C1[C@](O)(C)[C@@H](OC(=O)CCC)[C@H](C)O[C@H]1O[C@H]1[C@H](N(C)C)[C@@H](O)[C@H](O[C@@H]2[C@H]([C@H](O)CC(=O)O[C@H](C)C/C=C/C=C/[C@H](O)[C@H](C)C[C@@H]2CC=O)OC)O[C@@H]1C JZVYPSLDMXOITF-MJRCUCNNSA-N 0.000 description 19
150000001412 amines Chemical class 0.000 description 19
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
238000005917 acylation reaction Methods 0.000 description 18
101150041968 CDC13 gene Proteins 0.000 description 17
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
229960004144 josamycin Drugs 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
XJSFLOJWULLJQS-UHFFFAOYSA-N leucomycin A3 Natural products COC1C(OC(C)=O)CC(=O)OC(C)CC=CC=CC(O)C(C)CC(CC=O)C1OC1C(O)C(N(C)C)C(OC2OC(C)C(OC(=O)CC(C)C)C(C)(O)C2)C(C)O1 XJSFLOJWULLJQS-UHFFFAOYSA-N 0.000 description 12
239000005457 ice water Substances 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 10
239000012346 acetyl chloride Substances 0.000 description 10
239000000284 extract Substances 0.000 description 10
229960001170 rokitamycin Drugs 0.000 description 10
230000010933 acylation Effects 0.000 description 9
MXHTZQSKTCCMFG-UHFFFAOYSA-N n,n-dibenzyl-1-phenylmethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CC1=CC=CC=C1 MXHTZQSKTCCMFG-UHFFFAOYSA-N 0.000 description 9
229950001955 spiramycin i Drugs 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000002585 base Substances 0.000 description 8
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
230000000875 corresponding effect Effects 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
229940093499 ethyl acetate Drugs 0.000 description 7
235000019439 ethyl acetate Nutrition 0.000 description 7
XJSFLOJWULLJQS-NGVXBBESSA-N josamycin Chemical compound CO[C@H]1[C@H](OC(C)=O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 XJSFLOJWULLJQS-NGVXBBESSA-N 0.000 description 7
238000003756 stirring Methods 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 6
230000008034 disappearance Effects 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
IEMDOFXTVAPVLX-YWQHLDGFSA-N Leucomycin A1 Chemical group CO[C@H]1[C@H](O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 IEMDOFXTVAPVLX-YWQHLDGFSA-N 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 5
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 5
238000010992 reflux Methods 0.000 description 5
238000006884 silylation reaction Methods 0.000 description 5
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 4
SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
125000003172 aldehyde group Chemical group 0.000 description 4
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 4
238000005947 deacylation reaction Methods 0.000 description 4
FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000010828 elution Methods 0.000 description 4
238000000746 purification Methods 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000005051 trimethylchlorosilane Substances 0.000 description 4
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
UQDAEORWFCPQCU-UHFFFAOYSA-N acetic acid;oxolane;hydrate Chemical compound O.CC(O)=O.C1CCOC1 UQDAEORWFCPQCU-UHFFFAOYSA-N 0.000 description 3
238000006640 acetylation reaction Methods 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
230000000845 anti-microbial effect Effects 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000002955 isolation Methods 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000012264 purified product Substances 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
238000000926 separation method Methods 0.000 description 3
229910000077 silane Inorganic materials 0.000 description 3
238000001179 sorption measurement Methods 0.000 description 3
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 2
ACTOXUHEUCPTEW-CEUOBAOPSA-N 2-[(4r,5s,6s,7r,9r,10r,11e,13e,16r)-6-[(2s,3r,4r,5s,6r)-5-[(2s,4r,5s,6s)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2r,5s,6r)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-o Chemical compound O([C@H]1/C=C/C=C/C[C@@H](C)OC(=O)C[C@@H](O)[C@@H]([C@H]([C@@H](CC=O)C[C@H]1C)O[C@H]1[C@@H]([C@H]([C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1)N(C)C)O)OC)[C@H]1CC[C@H](N(C)C)[C@@H](C)O1 ACTOXUHEUCPTEW-CEUOBAOPSA-N 0.000 description 2
ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
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 2
XVTMRUKLMXPAKO-UHFFFAOYSA-N Leucomycin A4 Natural products C1C(O)(C)C(OC(=O)CCC)C(C)OC1OC1C(N(C)C)C(O)C(OC2C(C(OC(C)=O)CC(=O)OC(C)CC=CC=CC(O)C(C)CC2CC=O)OC)OC1C XVTMRUKLMXPAKO-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
DMUAPQTXSSNEDD-QALJCMCCSA-N Midecamycin Chemical compound C1[C@](O)(C)[C@@H](OC(=O)CC)[C@H](C)O[C@H]1O[C@H]1[C@H](N(C)C)[C@@H](O)[C@H](O[C@@H]2[C@H]([C@H](OC(=O)CC)CC(=O)O[C@H](C)C/C=C/C=C/[C@H](O)[C@H](C)C[C@@H]2CC=O)OC)O[C@@H]1C DMUAPQTXSSNEDD-QALJCMCCSA-N 0.000 description 2
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
VMPKXDLYZIGGMM-MXYURFFASA-N [(4r,5s,6s,7r,9r,10r,11e,13e,16r)-6-[(2s,3r,4r,5s,6r)-5-[(2s,4r,5s,6s)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)-1-oxacyclohexadeca-11,13-dien-4-yl] ac Chemical compound CO[C@H]1[C@H](OC(C)=O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1 VMPKXDLYZIGGMM-MXYURFFASA-N 0.000 description 2
229940022663 acetate Drugs 0.000 description 2
SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 2
235000019658 bitter taste Nutrition 0.000 description 2
230000036765 blood level Effects 0.000 description 2
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000013058 crude material Substances 0.000 description 2
239000009937 cyclo 3 Substances 0.000 description 2
230000020176 deacylation Effects 0.000 description 2
238000001914 filtration Methods 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 2
239000012429 reaction media Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
230000008707 rearrangement Effects 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
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239000003513 alkali Substances 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
ZWCKECHGNUHVBQ-UHFFFAOYSA-N benzene;ethyl acetate;hexane;methanol;propan-2-one Chemical compound OC.CC(C)=O.CCCCCC.CCOC(C)=O.C1=CC=CC=C1 ZWCKECHGNUHVBQ-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
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229950005779 carbomycin Drugs 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006704 dehydrohalogenation reaction Methods 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
229960003276 erythromycin Drugs 0.000 description 1
WJUDKPIZRQOBLE-QNNDZTFCSA-N espinomycin a2 Chemical compound CO[C@H]1[C@H](OC(=O)CC)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)C(C)C)[C@](C)(O)C2)[C@@H](C)O1 WJUDKPIZRQOBLE-QNNDZTFCSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000499 gel Substances 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229940091250 magnesium supplement Drugs 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229960002757 midecamycin Drugs 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229960002351 oleandomycin Drugs 0.000 description 1
RZPAKFUAFGMUPI-KGIGTXTPSA-N oleandomycin Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](C)C(=O)O[C@H](C)[C@H](C)[C@H](O)[C@@H](C)C(=O)[C@]2(OC2)C[C@H](C)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C RZPAKFUAFGMUPI-KGIGTXTPSA-N 0.000 description 1
235000019367 oleandomycin Nutrition 0.000 description 1
150000007530 organic bases Chemical group 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000036647 reaction Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
229960001294 spiramycin Drugs 0.000 description 1
235000019372 spiramycin Nutrition 0.000 description 1
229930191512 spiramycin Natural products 0.000 description 1
239000007858 starting material Substances 0.000 description 1
229940086735 succinate Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1

Landscapes

Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA327,269A 1978-05-10 1979-05-09 Antibiotiques macrolide 3"-acyles Expired CA1133475A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP53-55876		1978-05-10
JP5587678A JPS5946520B2 (ja)	1978-05-10	1978-05-10	新規３″−アシル化マクロライド系抗生物質

Publications (1)

Publication Number	Publication Date
CA1133475A true CA1133475A (fr)	1982-10-12

Family

ID=13011290

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA327,269A Expired CA1133475A (fr)	1978-05-10	1979-05-09	Antibiotiques macrolide 3"-acyles

Country Status (2)

Country	Link
JP (1)	JPS5946520B2 (fr)
CA (1)	CA1133475A (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6028984A (ja) *	1983-07-26	1985-02-14	Kyowa Hakko Kogyo Co Ltd	３″，４″−ジ−ｏ−アシルスピラマイシン１
JPS60126296A (ja) *	1983-12-13	1985-07-05	Kyowa Hakko Kogyo Co Ltd	３，３”，４”−トリ−ｏ−アシルスピラマイシン１
JPH0687881A (ja) *	1992-09-07	1994-03-29	Asahi Chem Ind Co Ltd	ロキタマイシン・一水和物結晶、及びその製造法

1978
- 1978-05-10 JP JP5587678A patent/JPS5946520B2/ja not_active Expired
1979
- 1979-05-09 CA CA327,269A patent/CA1133475A/fr not_active Expired

Also Published As

Publication number	Publication date
JPS54148793A (en)	1979-11-21
JPS5946520B2 (ja)	1984-11-13

Legal Events

Date	Code	Title	Description
1999-10-12	MKEX	Expiry

Publication	Publication Date	Title
CA2258606C (fr)	2003-05-27	Forme cristalline ii de la clarithromycine
WO1992006991A1 (fr)	1992-04-30	Erythromycine modifiee en 2' ou derive de cette substance
US4268665A (en)	1981-05-19	Derivatives of antibiotic tylosin
US4847242A (en)	1989-07-11	11-ether derivatives of erythromycins
CA1133475A (fr)	1982-10-12	Antibiotiques macrolide 3"-acyles
US4242504A (en)	1980-12-30	3"-Acylated macrolide antibiotics
US4933439A (en)	1990-06-12	Tylosin derivatives and processes for producing the same
KR20000057517A (ko)	2000-09-15	신규한 에리트로마이신 유도체, 그의 제조 방법 및 의약품으로서의 그의 용도
CA1196915A (fr)	1985-11-19	23-0-acyl-23-demycinosyldesmycosine
WO2002032917A1 (fr)	2002-04-25	Macrolides
US4804749A (en)	1989-02-14	20-O-Acyl-19,20-enolmacrolide antibiotic derivatives
KR830002484B1 (ko)	1983-10-26	3'' 아실화 매크롤라이드 항생물질의 제조방법
GB2171991A (en)	1986-09-10	Novel macrolide derivatives, process for preparing same, and antibacterial compositions thereof
US5091370A (en)	1992-02-25	Angolamycin derivatives
US4436733A (en)	1984-03-13	4"- And 3-ester derivatives of DMT and DMOT
CA1185968A (fr)	1985-04-23	Procede d'obtention de 23-monoesters d'omt et de dmt
Majer	1978	Macrolide antibiotics
GB2137983A (en)	1984-10-17	3-o-acyl-4}-deoxydesmycosin derivatives useful as antibiotics
EP0315720B1 (fr)	1993-09-15	Dérivés de 4"-désoxy-3"-déméthoxy-3"-méthylène-desmycosine
KR820001642B1 (ko)	1982-09-13	3＂,4＂-디아실타일로신 유도체류의 제조방법
CA2386534C (fr)	2003-05-27	Forme cristalline ii de la clarithromycine et son utilite
KR850001962B1 (ko)	1985-12-31	3"-아실화 매크롤라이드 항생물질의 제조방법
KR850001961B1 (ko)	1985-12-31	3"-아실화 매크롤라이드 항생물질의 제조방법
DK156071B (da)	1989-06-19	Fremgangsmaade til fremstilling af 3,3'',4''-triacyltylosinderivater
JPS6154038B2 (fr)	1986-11-20