JPS634553B2 - - Google Patents
Info
- Publication number
- JPS634553B2 JPS634553B2 JP7651080A JP7651080A JPS634553B2 JP S634553 B2 JPS634553 B2 JP S634553B2 JP 7651080 A JP7651080 A JP 7651080A JP 7651080 A JP7651080 A JP 7651080A JP S634553 B2 JPS634553 B2 JP S634553B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- mycinamicin
- methanol
- present
- reaction
- 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.)
- Expired
Links
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229930187734 mycinamicin Natural products 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 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
- 238000004440 column chromatography Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000187723 Micromonospora sp. Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、新規なマイシナミシン誘導体に関す
る。さらに詳しくは、本発明は、式
（式中、Ｒは水素原子または水酸基を示す）で表
わされる化合物またはその塩に関する。
マイシナミシン（Mycinamicin）は、ミクロ
モノスポラ・スピーシーズＡ―11725の産生する
塩基性16員環マクロライド系抗生物質の各成分、
即ちマイシナミシン，，およびの総称と
して命名されたものであり、各成分の化学構造は
J.Chem.Soc.Chem.Comm.，1980，119〜121に記
載されていて、最初は各々抗生物質A11725，
、ａおよびａと名付けられた（特開昭54−
148701号、特願昭54−31316号）。
上記の塩としては、医薬上許容できる塩であ
り、例えば塩酸、硫酸、リン酸などのの無機酸と
の塩、酢酸、プロピオン酸、酒石酸、クエン酸、
コハク酸、リンゴ酸、アスパラギン酸、グルタミ
ン酸、各種のスルホン酸などの有機酸との塩であ
る。その他非毒性塩も包含される。
上記の目的化合物〔〕およびその塩はグラム
陽性菌、グラム陰性菌およびマイコプラズマに対
し抗菌活性を有し、臨床上優れた感染治療効果の
期待される抗菌性物質であるばかりでなく、動物
の疾病の予防および治療剤として有用であり、飼
料添加用薬剤としても有用である。
本発明の目的化合物〔〕は、マイシナミシン
またはを不活性有機溶媒中パラジウム炭素触
媒の存在下水素添加することにより得られる。
不活性有機溶媒としては、メタノール、エタノ
ールなどの低級アルカノールが好ましい。水素添
加は通常常温常圧で行われ、３倍モルの水素ガス
を消費した時点で反応を停止すればよい。
得られた化合物〔〕を反応液から採取するに
は先ず触媒を去し、反応溶媒を留去した後、シ
リカゲル、活性アルミナ、吸着樹脂などの吸着剤
を用いるカラムクロマトグラフイーにより分離精
製することにより得られる。
次に、本発明の目的化合物〔〕の抗菌スペク
トラムを測定した結果を第１表に示す。
The present invention relates to novel mycinamicin derivatives. More specifically, the present invention provides the formula (wherein R represents a hydrogen atom or a hydroxyl group) or a salt thereof. Mycinamicin is a basic 16-membered ring macrolide antibiotic produced by Micromonospora sp. A-11725.
In other words, it was named as a generic term for mycinamicin, and the chemical structure of each component is
J.Chem.Soc.Chem.Comm., 1980, 119-121, and initially the antibiotics A11725,
, a and a (Japanese Unexamined Patent Application Publication No. 1989-1999)
No. 148701, Patent Application No. 1983-31316). The above salts include pharmaceutically acceptable salts, such as salts with inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, propionic acid, tartaric acid, citric acid,
It is a salt with organic acids such as succinic acid, malic acid, aspartic acid, glutamic acid, and various sulfonic acids. Other non-toxic salts are also included. The above target compound [ ] and its salts have antibacterial activity against gram-positive bacteria, gram-negative bacteria, and mycoplasma, and are not only antibacterial substances that are expected to have excellent clinical effects in treating infections, but also are effective against animal diseases. It is useful as a prophylactic and therapeutic agent, and is also useful as a feed additive agent. The object compound of the present invention [ ] can be obtained by hydrogenating mycinamicin or mycin in the presence of a palladium-carbon catalyst in an inert organic solvent. As the inert organic solvent, lower alkanols such as methanol and ethanol are preferred. Hydrogenation is usually carried out at room temperature and pressure, and the reaction may be stopped when three times the mole of hydrogen gas is consumed. To collect the obtained compound [] from the reaction solution, first remove the catalyst, distill off the reaction solvent, and then separate and purify it by column chromatography using an adsorbent such as silica gel, activated alumina, or adsorption resin. It is obtained by Next, Table 1 shows the results of measuring the antibacterial spectrum of the target compound of the present invention.
【表】【table】
【表】
次に、実施例を挙げて本発明の化合物〔〕の
製造例を具体的に説明する。
実施例 １
２，３，10，11，12，13―ヘキサヒドロマイシ
ナミシン
マイシナミシン1.05ｇをエタノールに溶か
し、10％パラジウム一炭素101mgの存在下室温、
常圧で４時間水素添加する。反応後、触媒を去
し、液を減圧下溶媒を留去する。残漬をシリカ
ゲル（50ｇ、メルク社製）のカラムクロマトグラ
フイーにてクロロホルム―メタノール―28％アン
モニア水（400：50：１）で溶出し、相当する区
分を減圧乾固して２，３，10，11，12，13―ヘキ
サヒドロマイシナミシン826mgを得る。
無定形白色粉末
Mass；701（M+）
〔α〕28 D−32.1（Ｃ＝1.0，メタノール）
IR；δKBr nax3460（OH）、1725、1705（CO）、1160、
1075cm-1
NMR；δCDCl3 ppn0.86（t.，16位CH3）、1.0〜1.3（５
×CH3）、2.28〔Ｎ（CH3）2〕、3.52（OCH3）、
3.62（OCH3）、4.22（d.1′位Ｈ）、4.51（d.，
1″位Ｈ）、4.92（d.d.d.，15位Ｈ）
実施例 ２
２，３，10，11，12，13―ヘキサヒドロマイシ
ナミシン
マイシナミシン1.05ｇをエタノール20mlに溶
かし、10％パラジウム―炭素触媒存在下室温、常
圧で水素添加する。反応後、触媒を去し、液
を減圧下溶媒を留去する。残渣をシリカゲル（50
ｇ、メルク社製）のカラムクロマトグラフイーに
てクロロホルム―メタノール―28％アンモニア
水、（4000：50：１）で溶出し、相当する区分を
減圧乾固して２，３，10，11，12，13―ヘキサヒ
ドロマイシナミシン799mgを得る。
無色形白色粉末
Mass；717（M+）
〔α〕28 D−20.5（Ｃ＝1.0，メタノール）
IR；δKBr nax3460（OH）cm-1
NMR；δCDCl3 ppn0.86〜1.3（６×CH3）、2.28〔Ｎ
（CH3）2〕3.56（OCH3）、3.61（OCH3）、4.21
（d.，1′位Ｈ）4.58（d.，1″位Ｈ）、4.85（ｄ，
ｄ，15位Ｈ）[Table] Next, production examples of the compound [] of the present invention will be specifically explained with reference to Examples. Example 1 2,3,10,11,12,13-hexahydromycinamicin 1.05 g of mycinamicin was dissolved in ethanol and heated at room temperature in the presence of 101 mg of 10% palladium on carbon.
Hydrogenate at normal pressure for 4 hours. After the reaction, the catalyst is removed and the solvent is distilled off from the liquid under reduced pressure. The residue was eluted with chloroform-methanol-28% aqueous ammonia (400:50:1) using silica gel (50 g, manufactured by Merck & Co.) column chromatography, and the corresponding fractions were dried under reduced pressure to obtain 2, 3, 826 mg of 10,11,12,13-hexahydromycinamicin is obtained. Amorphous white powder Mass; 701 (M + ) [α] 28 D −32.1 (C = 1.0, methanol) IR; δ KBr nax 3460 (OH), 1725, 1705 (CO), 1160,
1075cm -1 NMR; δ CDCl3 ppn 0.86 (t., 16th CH 3 ), 1.0-1.3 (5
×CH 3 ), 2.28 [N(CH 3 ) 2 ], 3.52 (OCH 3 ),
3.62 (OCH 3 ), 4.22 (d.1′ H), 4.51 (d.,
1″ position H), 4.92 (ddd, 15th position H) Example 2 2,3,10,11,12,13-hexahydromycinamicin 1.05 g of mycinamicin was dissolved in 20 ml of ethanol, and 10% palladium-carbon catalyst was present. Hydrogenation is carried out at room temperature and normal pressure. After the reaction, the catalyst is removed and the solvent is distilled off from the liquid under reduced pressure. The residue is purified by silica gel (50
(Merck & Co., Ltd.) column chromatography, eluting with chloroform-methanol-28% aqueous ammonia (4000:50:1), and drying the corresponding fractions under reduced pressure to obtain 2, 3, 10, 11, 799 mg of 12,13-hexahydromycinamicin is obtained. Colorless white powder Mass; 717 (M + ) [α] 28 D −20.5 (C = 1.0, methanol) IR; δ KBr nax 3460 (OH) cm -1 NMR; δ CDCl3 ppn 0.86-1.3 (6×CH 3 ), 2.28 [N
(CH 3 ) 2 ] 3.56 (OCH 3 ), 3.61 (OCH 3 ), 4.21
(d., 1′ position H) 4.58 (d., 1″ position H), 4.85 (d.
d, 15th place H)
Claims (1)
表わされる化合物またはその塩。[Claims] 1 formula (wherein R represents a hydrogen atom or a hydroxyl group) or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7651080A JPS5718693A (en) | 1980-06-05 | 1980-06-05 | Hexahydromycinamicin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7651080A JPS5718693A (en) | 1980-06-05 | 1980-06-05 | Hexahydromycinamicin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5718693A JPS5718693A (en) | 1982-01-30 |
| JPS634553B2 true JPS634553B2 (en) | 1988-01-29 |
Family
ID=13607248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7651080A Granted JPS5718693A (en) | 1980-06-05 | 1980-06-05 | Hexahydromycinamicin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5718693A (en) |
-
1980
- 1980-06-05 JP JP7651080A patent/JPS5718693A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5718693A (en) | 1982-01-30 |
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