WO2004101592A1 - Procede de production de derives d'erithromycine a - Google Patents
Procede de production de derives d'erithromycine a Download PDFInfo
- Publication number
- WO2004101592A1 WO2004101592A1 PCT/JP2004/006985 JP2004006985W WO2004101592A1 WO 2004101592 A1 WO2004101592 A1 WO 2004101592A1 JP 2004006985 W JP2004006985 W JP 2004006985W WO 2004101592 A1 WO2004101592 A1 WO 2004101592A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carbon atoms
- group
- potassium
- sodium
- substituted
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical class 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 title abstract description 23
- 238000000034 method Methods 0.000 title abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 66
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 26
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 14
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims abstract description 7
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims abstract description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 239000001257 hydrogen Substances 0.000 abstract description 7
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000001589 carboacyl group Chemical group 0.000 abstract 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 229960003276 erythromycin Drugs 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 9
- 229930006677 Erythromycin A Natural products 0.000 description 7
- 150000005676 cyclic carbonates Chemical class 0.000 description 7
- 239000012043 crude product Substances 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- -1 3-pyridyl acetyl Chemical group 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000011172 small scale experimental method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Definitions
- the present invention relates to a method for producing a 91-dexoxo 9-hydroxyerythromycin A 11,12-cyclic force monoponate derivative useful as a synthetic intermediate for a novel erythromycin A derivative.
- the reaction solvent is changed from methanol to ethanol, isopropanol, tetrahydrofuran or a mixed solvent thereof having low reactivity with sodium borohydride. It is known that hydrogen generation can be prevented by replacing it. Disclosure of the invention
- An object of the present invention is to reduce the 9-position propyl group of an erythromycin A11,12_ cyclic carbonate derivative to a 9-deoxo, 9-hydroxyerythromycin A11,12-cyclic carbonate derivative.
- An object of the present invention is to provide an industrially safe and useful production method for guiding.
- erythromycin A 11, 12-cyclic carbonate components are used to suppress the inactivation of reagents due to the reaction between sodium borohydride and methanol, the generation of hydrogen, and the reduction in yield due to side reactions. It is an object of the present invention to provide a production method useful for industrially obtaining 9-deoxo-9-hydroxyerythromycin A11,12-cyclic carbonate derivatives in a safe and high yield.
- the present inventors have conducted intensive studies, and as a result, by adding a certain base to a methanol solution of erythromycin A11,12-cyclic carbonate derivative, The present inventors have found a method for industrially producing a 9-deoxo-9-hydroxyerythromycin A11,12-cyclic carbonate derivative in a safe and high yield while preventing generation of hydrogen, and completed the present invention.
- the present invention provides a formula
- R1 is a hydrogen atom, an alkanoyl group having 1 to 5 carbon atoms, an aromatic ring having 5 to 12 carbon atoms, or an Al force having 1 to 5 carbon atoms substituted with a heterocyclic ring having 3 to 9 carbon atoms.
- the compound (I) represented by the formula (I) is obtained by converting sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxy.
- sodium borohydride in methanol to which one or more bases selected from potassium, potassium ethoxide or potassium tert-butoxide have been added
- the alkanoyl group having 1 to 5 carbon atoms in the present invention is, for example, a formyl group, an acetyl group, a propionyl group, a butyryl group, an isoptyryl group, a valeryl group, an isovaleryl group or a pivaloyl group, and has 5 to 1 carbon atoms.
- An aromatic ring having 2 or a heterocyclic ring having 3 to 9 carbon atoms is, for example, a phenyl group, a naphthyl group, an imidazolyl group or a pyridyl group, and an alkyl group having 1 to 4 carbon atoms is, for example, methyl Group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group or tert-butyl group; the aromatic ring having 6 to 10 carbon atoms is, for example, a phenyl group or a naphthyl group;
- the alkyl group having 1 to 4 carbon atoms substituted with an aromatic ring having 6 to 10 is, for example, a benzyl group or a phenethyl group.
- the present invention relates to a production method shown in the following reaction scheme.
- the present invention relates to a method for producing a compound (II) from a compound (I) described in US Pat. No. 5,866,549.
- Step 1 A methanol solution to which one or more bases selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide or potassium tert-butoxide are added ( The base concentration was adjusted to 0.001 to 0.5 M), and the methanol solution was divided into two. Sodium (1-5 equivalents) is dissolved, and on the other hand, the compound described in US Pat. No. 5,866,549 (formula (I)) is dissolved, and both solutions are mixed and reacted at 0 ° C. to 60 ° C. The compound represented by (II) can be obtained.
- Example 1 A methanol solution to which one or more bases selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide or potassium tert-butoxide are added ( The base concentration was adjusted to 0.001 to 0.5 M), and the methanol solution was divided into two.
- the reaction mixture was separated by adding 19 Oml of a 20% aqueous ammonium chloride solution and 20 Om1 of ethyl acetate.
- the aqueous layer was extracted with 10 Oml of toluene, combined with the above ethyl acetate layer, washed twice with saturated brine (5 Oml), and concentrated under reduced pressure to obtain 19 g of a crude product.
- Erythromycin A 11,12 Dissolve 50 g (66 mMol) of cyclic carbonate in 10 Om1 of a 0.01 M sodium hydroxide / methanol solution, add 7.5 g of sodium borohydride (0.2 Omo1,3 eq ) Dissolved in 0.01 M sodium hydroxide / methanol solution was added dropwise while controlling the temperature so that the internal temperature did not exceed 3 Ot, and stirring was continued for 2 hours.
- Erythromycin A 11,12_cyclic carbonate 2 Dissolve Og (2.6 mmo 1) in 1 Om1 of ethanol and, at room temperature, 0.30 g of sodium borohydride (7.9 mmo and 2.0 eq) was added and stirring was continued overnight. After adding 50 ml of water to the reaction solution and extracting twice with 50 ml of ethyl acetate, the ethyl acetate layer was washed with 100 ml of saturated saline solution and dried over anhydrous magnesium sulfate.
- the present invention relates to a method for preparing sodium hydroxide, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide, in a methanol solution of erythromycin A 11, 12_cyclic carbonate derivative and sodium borohydride, By adding one or more bases selected from potassium ethoxide or potassium tert-butoxide, it is safe and industrially practicable 91-deoxo, 9-hydroxyerythromycin A11,12-cyclic This is extremely useful as a method for producing a carbonate derivative in high yield.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne un procédé de production de dérivés carbonatés 11, 12-cycliques de 9-désoxo-9-hydroxyérythromycine A qui peuvent être utilisés comme intermédiaires dans la synthèse de nouveau dérivés d'érithromycine A. Ce procédé consiste à faire réagir un composé correspondant à la formule générale (I) avec un borohydrure de sodium dans un solvant à base de méthanol contenant un ou deux éléments choisis parmi l'hydroxyde de sodium, l'hydroxyde de potassium, le méthoxyde de sodium, l'éthoxyde de sodium, le méthoxyde de potassium, l'éthoxyde de potassium et le butoxyde tertiaire de potassium. Dans ladite formule, R1 représente hydrogène, alcanoyl C1-5, alcanoyl C1-5 substitué par un cycle aromatique de 5 à 12 atomes de carbone ou un hétérocycle de 3 à 9 atomes de carbone, ou silyle substitué par un à trois groupes sélectionnés parmi alkyle C1-4, des cycles aromatiques possédant 6 à 10 atomes de carbone et des groupes alkyle C1-4 substitués par des cycles aromatiques possédant 6 à 10 atomes de carbone.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003139718 | 2003-05-19 | ||
| JP2003-139718 | 2003-05-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004101592A1 true WO2004101592A1 (fr) | 2004-11-25 |
Family
ID=33447352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2004/006985 WO2004101592A1 (fr) | 2003-05-19 | 2004-05-17 | Procede de production de derives d'erithromycine a |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2004101592A1 (fr) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58159499A (ja) * | 1982-03-01 | 1983-09-21 | フアイザ−・インコ−ポレ−テツド | 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 |
| JPH04149152A (ja) * | 1990-10-09 | 1992-05-22 | Kanegafuchi Chem Ind Co Ltd | ３，４―ジヒドロキシ酪酸エステル誘導体の製造法 |
| JPH06345793A (ja) * | 1993-06-10 | 1994-12-20 | Asahi Chem Ind Co Ltd | 抗生物質ｌ５３−１８ａ誘導体 |
| JPH10500954A (ja) * | 1994-05-23 | 1998-01-27 | セプラコー，インコーポレイテッド | 光学純正アルブテロールの異性体選択性製剤 |
| WO1998013373A1 (fr) * | 1996-09-24 | 1998-04-02 | Taisho Pharmaceutical Co., Ltd. | Derives d'erythromycine a |
-
2004
- 2004-05-17 WO PCT/JP2004/006985 patent/WO2004101592A1/fr not_active Application Discontinuation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58159499A (ja) * | 1982-03-01 | 1983-09-21 | フアイザ−・インコ−ポレ−テツド | 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 |
| JPH04149152A (ja) * | 1990-10-09 | 1992-05-22 | Kanegafuchi Chem Ind Co Ltd | ３，４―ジヒドロキシ酪酸エステル誘導体の製造法 |
| JPH06345793A (ja) * | 1993-06-10 | 1994-12-20 | Asahi Chem Ind Co Ltd | 抗生物質ｌ５３−１８ａ誘導体 |
| JPH10500954A (ja) * | 1994-05-23 | 1998-01-27 | セプラコー，インコーポレイテッド | 光学純正アルブテロールの異性体選択性製剤 |
| WO1998013373A1 (fr) * | 1996-09-24 | 1998-04-02 | Taisho Pharmaceutical Co., Ltd. | Derives d'erythromycine a |
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