JPS61126087A - Production of 2alpha-methyl-2beta-(1,2,3-triazol-1-yl) methylpenam-3alpha-carboxylic acid derivative - Google Patents
Production of 2alpha-methyl-2beta-(1,2,3-triazol-1-yl) methylpenam-3alpha-carboxylic acid derivativeInfo
- Publication number
- JPS61126087A JPS61126087A JP59248985A JP24898584A JPS61126087A JP S61126087 A JPS61126087 A JP S61126087A JP 59248985 A JP59248985 A JP 59248985A JP 24898584 A JP24898584 A JP 24898584A JP S61126087 A JPS61126087 A JP S61126087A
- Authority
- JP
- Japan
- Prior art keywords
- methylpenam
- carboxylic acid
- acid derivative
- methyl
- formula
- 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.)
- Pending
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、一般式
〔式中、Ｒはペニシリンカルボキシル保護基を示す。〕
で表わされる２α−メチル−２β−（１，２，３−トリ
アゾール−１−イル）メチルペナム−３α−カルボン酸
誘導体の工業的に有利な新規製造法に関する。DETAILED DESCRIPTION OF THE INVENTION Industrial Field of Application The present invention relates to a compound of the general formula [wherein R represents a penicillin carboxyl protecting group]. ] The present invention relates to a new industrially advantageous method for producing a 2α-methyl-2β-(1,2,3-triazol-1-yl)methylpenam-3α-carboxylic acid derivative represented by the following.
一般式（Ｉ）の化合物は、β−ラクタマーゼ阻害作用を
有し、医薬品として有用である。The compound of general formula (I) has a β-lactamase inhibitory effect and is useful as a pharmaceutical.
１１立盈Ｉ
一般式（工・）の化合物の製造方法としては、特開昭５
９−１４８７８８号に開示された方法が知られている。11 Standing I As a method for producing a compound of the general formula (Eng.), JP-A No. 5
The method disclosed in No. 9-148788 is known.
発明が解決しようとする問題点
特開昭５９−１４８７８８号には、２β−アジドメチル
−２α−メチルペナム−３α−カルボン！Ｉ！誘導体と
アセチレン誘導体の反応による一般式（Ｉ＞の化合物の
製造法として、次に示す２つの方法が開示されている。Problems to be Solved by the Invention JP-A-59-148788 discloses 2β-azidomethyl-2α-methylpenam-3α-carvone! I! The following two methods have been disclosed as methods for producing compounds of general formula (I>) by reacting derivatives with acetylene derivatives.
くＡ法〉
一般式
〔式中、Ｒは前記に同じ。〕
で表わされる化合物にトリメチルシリルアセチレンを封
管中反応させ、一般式
〔式中、Ｒは前記に同じ。〕で表わされる化合物を得、
さらにＮ、Ｎ−ジメチルホルムアミド中、触媒の１８−
クラウン−６存在下にフッ化カリウムにて脱トリメチル
シリル化し、ざらにシリカゲルカラムクロマトグラフィ
ーにより精製して一般式（１）の化合物を得る方法。Method A> General formula [wherein R is the same as above. ] A compound represented by the following is reacted with trimethylsilylacetylene in a sealed tube, and the compound is reacted with the general formula [wherein R is the same as above]. ] to obtain a compound represented by
Furthermore, in N,N-dimethylformamide, the 18-
A method for obtaining a compound of general formula (1) by removing trimethylsilylation with potassium fluoride in the presence of Crown-6 and then purifying it by rough silica gel column chromatography.
く方法〉
一般式（Ｉｒ）で表わされる化合物に塩化メチレン中、
トリメチルシリルアセチレンを封管中反応させて、生成
物をシリカゲルカラムクロマトグラフィーにて精製して
一般式（Ｉ）の化合物を得る方法−
しかしながら、これら２つの方法については、工業的製
造上いくつかの問題点が指摘される。すなわち、Ａ法に
は、原料となるトリメチルシリルアセチレン、１８−ク
ラウン−６が高価である事、目的化合物を得るのに製造
工程を２段階必要とし、トリメチルシリル基を脱離する
工程の収率が低い事、従って分離操作としてカラムクロ
マトグラフィーによる精製の工程が必要な事等の問題が
ある。Method> A compound represented by the general formula (Ir) is added in methylene chloride,
A method of reacting trimethylsilylacetylene in a sealed tube and purifying the product using silica gel column chromatography to obtain a compound of general formula (I).However, these two methods have several problems in industrial production. Points are pointed out. In other words, method A requires expensive raw material trimethylsilylacetylene, 18-crown-6, requires two manufacturing steps to obtain the target compound, and has a low yield in the step of eliminating the trimethylsilyl group. Therefore, there are problems such as the necessity of a purification step by column chromatography as a separation operation.
又方法には、Ａ法と同様にトリメチルシリルアセチレン
が古価である事、低収率の為カラムクロマトグラフィー
の＃ｌ製工程が必要な事等の問題点がある。In addition, this method, like Method A, has problems such as the fact that trimethylsilylacetylene is old and that a #1 column chromatography step is required due to the low yield.
以上の問題点は、本発明目的化合物を工業的に有利に製
造するために、解決することが切望されている事項であ
る。The above-mentioned problems are urgently desired to be solved in order to industrially advantageously produce the object compound of the present invention.
問題点を解決する為の手段
本発明者らは、一般式（Ｉ）で表わされる２α−メチル
−２β−（１，２，３−トリアゾール−１−イル）メチ
ルペナム−３α−カルボンａＸ導体の工業的に有利な製
造法について鋭意研究した結果、下記製造法が上記問題
点を解決した優゛れた方法である事を見い出し、本発明
を完成するに至った。Means for Solving the Problems The present inventors have developed a 2α-methyl-2β-(1,2,3-triazol-1-yl)methylpenam-3α-carbon aX conductor represented by the general formula (I). As a result of intensive research into economically advantageous manufacturing methods, we have discovered that the following manufacturing method is an excellent method that solves the above problems, and have completed the present invention.
発明の 成及び効果
本発明は、一般式
Ｃ式中、Ｒは前記に同じ。〕
で表わされる２β−アジドメチル−２α−メチルペナム
−３α−カルボン酸誘導体にアセチレンを作用させて一
般式
〔式中、Ｒは前記に同じ。〕
で表わされる２α−メチル−２β−（１，２，３−トリ
アゾール−１−イル）メチルペナム−３α−カルボンｍ
誘導体を得ることを特徴とする２α−メチル−２β−（
１，２，３−トリアゾール−１−イル）メチルペナム−
３α−カルボン酸誘導体の製造法に係る。Effects and Effects of the Invention The present invention provides a general formula C in which R is the same as defined above. ] The 2β-azidomethyl-2α-methylpenam-3α-carboxylic acid derivative represented by the formula is reacted with acetylene to form the general formula [wherein R is the same as above]. ] 2α-methyl-2β-(1,2,3-triazol-1-yl)methylpenam-3α-carvone m
2α-methyl-2β-(
1,2,3-triazol-1-yl)methylpenam-
The present invention relates to a method for producing a 3α-carboxylic acid derivative.
本発明において、Ｒで示されるペニシリンカルボキシル
保護基は、通常公知のものでよく、その代表例は特開昭
４９−８１３８０号公報及びエッチ゛・イー・フライン
編 セファロスポリン アンド ペニシリンズ、ケミス
トリー アンド バイ ・オロジー（１９７２年
アカデミツクブレス社発行）に記載されている。具体
的には、エチル、プロピル、ｔｅｒｔ−ブチル、トリク
ロロエチル基等の置換又は非置換アルキル基、ベンジル
、ジフェニルメチル、ｐ−ニトロぢンジル基等の置換又
は非置換アルキル基、アセトキシメチル、ベンゾイルオ
キシメチル基等のアシルオキシアルキル基、メトキシメ
チル基等のアルコキシアルキル基、その他テトラヒドロ
ピラニル基、ジメチルアミノエチル基、ジメチルクロロ
シリル基、トリクロロシリル基等を例示できる。In the present invention, the penicillin carboxyl protecting group represented by R may be a commonly known one, and typical examples thereof include JP-A-49-81380 and H. E. Fryne, Cephalosporins and Penicillins, Chemistry and Biological Sciences. - Described in Ology (1972, published by Academic Press). Specifically, substituted or unsubstituted alkyl groups such as ethyl, propyl, tert-butyl, trichloroethyl, substituted or unsubstituted alkyl groups such as benzyl, diphenylmethyl, p-nitronzyl, acetoxymethyl, benzoyloxy, etc. Examples include an acyloxyalkyl group such as a methyl group, an alkoxyalkyl group such as a methoxymethyl group, a tetrahydropyranyl group, a dimethylaminoethyl group, a dimethylchlorosilyl group, and a trichlorosilyl group.
本発明においては、適当な溶媒中一般式（Ｉ）で示され
る２β−アジドメチル−２α−メチルペナム−３α−カ
ルボンｌ誘導体とアセチレンとを密閉容器中加熱するこ
とによって、一般式（１）で示される２α−メチル−２
β−（１，２，３−トリアゾール−１−イル）メチルペ
ナム−３α−カルボンＩ！Ｉ！２誘導体を得る。使用す
る溶媒としては、塩化メチレン、クロロホルム等のハロ
ゲン化炭化水素類、アセトン、メチルエチルケトン等の
脂肪族ケトン類等を例示できる。これらの内、アセトン
を使用するのが特に好ましい。又、一般式（Ｉ）の原料
化合物とアセチレンの使用割合は、通常前者対後者がモ
ル比で１対５〜５０程度、好ましくは１対１０〜４０で
ある。又反応温度は通常５０〜１００℃程度、好ましく
は７５〜９０℃で行うのがよく、圧力は通常９〜１５気
圧程度、好ましくは１１〜１３気圧であり、反応は通常
１０〜４０時間程度、好ましい条件下では２０〜２５時
間で完結する。反応は、通常定量的に進行する。In the present invention, the 2β-azidomethyl-2α-methylpenam-3α-carboxylic derivative represented by the general formula (I) and acetylene are heated in a closed container in a suitable solvent, thereby producing a compound represented by the general formula (1). 2α-methyl-2
β-(1,2,3-triazol-1-yl)methylpenam-3α-carvone I! I! 2 derivatives are obtained. Examples of the solvent used include halogenated hydrocarbons such as methylene chloride and chloroform, and aliphatic ketones such as acetone and methyl ethyl ketone. Among these, it is particularly preferred to use acetone. The molar ratio of the raw material compound of formula (I) to acetylene is usually about 1:5 to 50, preferably 1:10 to 40. The reaction temperature is usually about 50 to 100°C, preferably 75 to 90°C, the pressure is usually about 9 to 15 atm, preferably 11 to 13 atm, and the reaction is usually carried out for about 10 to 40 hours. Under favorable conditions, the process is complete in 20-25 hours. The reaction usually proceeds quantitatively.
かくして得られる一般式（１）の本発明目的化合物は、
非常に轟純度である。従って、これを更に他の反応に供
する場合には、ｆｉ製を必要としない。即ち、本発明法
によって得られた一般式（Ｉ）の化合物は、精製する事
なく次の製造工程、例えば脱エステル反応、エステル化
反応、塩形成反応等の工程にそのまま使用できる。The object compound of the present invention of general formula (1) thus obtained is:
Very pure purity. Therefore, when this is further subjected to other reactions, the fi product is not required. That is, the compound of general formula (I) obtained by the method of the present invention can be used as it is in the next production process, such as deesterification reaction, esterification reaction, salt formation reaction, etc., without purification.
本発明法により、次の様な効果が得られる。即ち、本発
明法において原料として使用されるアセチレンはトリメ
チルシリルアセチレンと比べて廉価であり、又１８−ク
ラウン−６等のｌ！ｉｌｉ！ｊな触媒を必要としない。The method of the present invention provides the following effects. That is, the acetylene used as a raw material in the method of the present invention is less expensive than trimethylsilylacetylene, and l! ili! Does not require a special catalyst.
又、反応が定量的に進行し、高収率である為、再結晶や
カラムクロマトグラフィー等の分離１１＠工程を必要と
しないので、工業的製造においては、分離精製工程に付
随する溶媒の回収工程等を省略する事ができる等の優れ
た作用を期待しうるものである。In addition, since the reaction proceeds quantitatively and has a high yield, separation steps such as recrystallization and column chromatography are not required, so in industrial production, it is necessary to recover the solvent that accompanies the separation and purification step. Excellent effects such as the ability to omit processes and the like can be expected.
１１１１翌ユ１１
以下、実施例及び比較例（前記Ａ法及びＢ法）を挙げて
、本発明を更に具体的に説明する。1111Next U11 Hereinafter, the present invention will be explained in more detail with reference to Examples and Comparative Examples (method A and method B).
実施例１
２α−メチル−２β−（１，２，３−トリアシー／レー
１−イル）メチルペナム−３α−カルボンｍｉ、１−ジ
オキシド ｐ−ニトロベンジルエステルの製造
一７８℃にて、アセトン２０ｗ１１２にアセチレンガス
７ｇを注入し、１００−の耐圧容器に入れ、−７８℃に
てアセトン１０ｍ１２に溶解した２β−アジドメチル−
２α−メチルペナム−３α−カルボン酸 １，１−ジオ
キシド ｐ−ニトロベンジルエステル１２Ｃ１を加え、
容器を密封した後、８・５℃にて２０時間加熱した。こ
の時の初圧は１１．０気圧であった。次いで室温に戻し
、析出した結晶を枦取し、酢酸エチルにて洗浄し、ｔＰ
液を減圧上濃縮し、残渣に酢酸エチル１０或を加え、０
〜５℃にて放置、析出した結晶を枦取し、先の結晶と合
し、融点１８２〜１８４℃の２α−メチル−２β−（１
，２，３−トリアゾール−１−イル）メチルペナム−３
α−カルボンＩ！１．１−ジオキシド ｐ−ニトロベン
ジルエステルの無色結晶１２．１ｇを得た（収率９５％
）。Example 1 Production of 2α-methyl-2β-(1,2,3-triacy/ley-1-yl)methylpenam-3α-carvone mi,1-dioxide p-nitrobenzyl ester - At 78°C, acetylene was added to acetone 20w112. 7 g of gas was injected into a 100-cm pressure container, and 2β-azidomethyl- dissolved in 10 ml of acetone was heated at -78°C.
Add 2α-methylpenam-3α-carboxylic acid 1,1-dioxide p-nitrobenzyl ester 12C1,
After the container was sealed, it was heated at 8.5° C. for 20 hours. The initial pressure at this time was 11.0 atm. Then, the temperature was returned to room temperature, the precipitated crystals were collected, washed with ethyl acetate, and tP
The liquid was concentrated under reduced pressure, and 10 g of ethyl acetate was added to the residue.
After standing at ~5°C, the precipitated crystals were collected and combined with the previous crystals to form 2α-methyl-2β-(1
,2,3-triazol-1-yl)methylpenam-3
α-Carvone I! 12.1 g of colorless crystals of 1,1-dioxide p-nitrobenzyl ester were obtained (yield 95%).
).
赤外吸収スペクトル（ＫＢｒ）ニ
ジ、ａｘ （ｃ＋＋−’）−１８００，１７６０゜核磁
気共鳴スペクトル（ＣＤＣ（１３）：δ（＋）ｌ）Ｉ
）−１，２６（３Ｈ，ｓ）、３．５〜３．６ （２Ｈ，
ｍ）、
４．６６ （ＩＨ，ｓ）、
４．６〜４．７ （ＩＨ，ｍ）、
５．０７ （２Ｈ，ｓ）、
５．３６ （２日、ｓ）、
７．６１ （２Ｈ，ｄ“）、
７．７４ （１Ｈ，ｄ）、
７．８０ （ＩＨ，ｄ）、
８．２８ （２Ｈ，ｄ）。Infrared absorption spectrum (KBr), ax (c++-')-1800, 1760° Nuclear magnetic resonance spectrum (CDC(13): δ(+)l)I
)-1,26 (3H, s), 3.5-3.6 (2H,
m), 4.66 (IH, s), 4.6-4.7 (IH, m), 5.07 (2H, s), 5.36 (2 days, s), 7.61 (2H, d"), 7.74 (1H, d), 7.80 (IH, d), 8.28 (2H, d).
比較例１
２α−メチル−２β−（１，２，３−トリアゾール−１
−イル）メチルペナム−３α−カルボン酸 １，１−ジ
オキシド ｐ−ニトロベンジルエステルの製造（Ａ法）
２β−アジドメチル−２α−メチルペナム−３α−カル
ボン！！１．１−ジオキシド ｐ−ニトロベンジルエス
テル４０９ ｍｇとトリメチルシリルアセチレン８８２
１１Ｊを封管中、９０〜９５℃で２０時間反応させた。Comparative Example 1 2α-methyl-2β-(1,2,3-triazole-1
-yl) Methylpenam-3α-carboxylic acid 1,1-dioxide Production of p-nitrobenzyl ester (Method A) 2β-azidomethyl-2α-methylpenam-3α-carvone! ! 1.1-dioxide p-nitrobenzyl ester 409 mg and trimethylsilylacetylene 882
11J was reacted in a sealed tube at 90 to 95°C for 20 hours.
反応混合物を減圧上濃縮し、４９７１１１ＣＩの２α−
メチル−２β−（４−トリメチルシリル−１，２，３−
トリアゾール−１−イル）メチルペナム−３α−カルボ
ン酸 １，１−ジオキシド ｐ−ニトロベンジルエステ
ルを得たく収率９８％）。The reaction mixture was concentrated under reduced pressure to obtain 2α- of 497111CI.
Methyl-2β-(4-trimethylsilyl-1,2,3-
Triazol-1-yl) methylpenam-3α-carboxylic acid 1,1-dioxide p-nitrobenzyl ester was obtained (yield 98%).
次いで２α−メチル−２β−（４−トリメチルシリル−
１，２，３−トリアゾール−１−イル）メチルペナム−
３α−カルボン酸 １，１−ジオキシド ｐ−ニトロベ
ンジルエステル４９７＋ａ、１８−クラウン−６（１，
４，７，１０，１３゜１６−ヘキサオキサシクロオクタ
デカン）１３ＩＩ１ｇ及びフッ化カリウム６３ｍｇをＮ
、Ｎ−ジメチルホルムアミド２．８−中、５０〜６０℃
にて５．５時間撹拌した。反応液を氷水にそそぎ、酢酸
エチルにて抽出し、酢酸エチル層を硫酸マグネシウムに
て乾燥後、減圧上濃縮し、残渣をシリカゲルカラムクロ
マトグラフィーにより精製し、２α−メチル−２β−（
１，２，３−トリアゾール−１−イル）メチルペナム−
３α−カルボン酸１，１−ジオキシド ｐ−ニトロベン
ジルエステル１３１１Ｇを得た（収率３１％）。Then 2α-methyl-2β-(4-trimethylsilyl-
1,2,3-triazol-1-yl)methylpenam-
3α-carboxylic acid 1,1-dioxide p-nitrobenzyl ester 497+a, 18-crown-6 (1,
4,7,10,13゜16-hexaoxacyclooctadecane) 1g and 63mg of potassium fluoride were added to N
, in N-dimethylformamide 2.8-50-60°C
The mixture was stirred for 5.5 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The ethyl acetate layer was dried over magnesium sulfate, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2α-methyl-2β-(
1,2,3-triazol-1-yl)methylpenam-
3α-carboxylic acid 1,1-dioxide p-nitrobenzyl ester 1311G was obtained (yield 31%).
このものの融点、赤外吸収スペクトル及び核磁気共鳴ス
ペクトルは実施例１のそれとすべて一致した。The melting point, infrared absorption spectrum, and nuclear magnetic resonance spectrum of this product all matched those of Example 1.
比較例２
２α−メチル−２β−（１，２，３−トリアゾール−１
−イル）メチルペナム−３α−カルボン酸 １，１−ジ
オキシド ｐ−ニトロベンジルエステルの製造（Ｂ法）
２β−アジドメチル−２α−メチルペナム−３α−カル
ボン酸 １，１−ジオキシド ｐ−ニトロベンジルエス
テル
セチレン
中９５℃で２０時間反応させた。反応液を減圧上濃縮し
、残渣をシリカゲルカラムクロマトグラフィーにより精
製し、目的化合物である２α−メチル−２β−（１．２
．３−トリアゾール−１−イル）メチルペナム−３α−
カルボンｍ １，１−ジオキシド ｐ−ニトロベンジ
ルエステル８７１１３を得た（収率２０％）。このもの
の融点、赤外吸収スペクトル及び核磁気共鳴スペクトル
は実施例１のそれとすべて一致した。Comparative Example 2 2α-methyl-2β-(1,2,3-triazole-1
-yl) Methylpenam-3α-carboxylic acid 1,1-dioxide Production of p-nitrobenzyl ester (Method B) 2β-azidomethyl-2α-methylpenam-3α-carboxylic acid 1,1-dioxide p-nitrobenzyl ester in cetylene The reaction was carried out at 95°C for 20 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the target compound, 2α-methyl-2β-(1.2
．． 3-triazol-1-yl)methylpenam-3α-
Carvone m 1,1-dioxide p-nitrobenzyl ester 87113 was obtained (yield 20%). The melting point, infrared absorption spectrum, and nuclear magnetic resonance spectrum of this product all matched those of Example 1.
（以 上） −１４．・シ″(that's all) -14.・S
Claims (1)
−３α−カルボン酸誘導体にアセチレンを作用させて一
般式 ▲数式、化学式、表等があります▼ 〔式中、Ｒは前記に同じ。〕 で表わされる２α−メチル−２β−（１，２，３−トリ
アゾール−１−イル）メチルペナム−３α−カルボン酸
誘導体を得ることを特徴とする２α−メチル−２β−（
１，２，３−トリアゾール−１−イル）メチルペナム−
３α−カルボン酸誘導体の製造法。(1) General formula▲ Numerical formulas, chemical formulas, tables, etc.▼ [In the formula, R represents a penicillin carboxyl protecting group. ] The 2β-azidomethyl-2α-methylpenam-3α-carboxylic acid derivative represented by is reacted with acetylene to form the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R is the same as above. 2α-methyl-2β-(1,2,3-triazol-1-yl)methylpenam-3α-carboxylic acid derivative represented by
1,2,3-triazol-1-yl)methylpenam-
Method for producing 3α-carboxylic acid derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59248985A JPS61126087A (en) | 1984-11-26 | 1984-11-26 | Production of 2alpha-methyl-2beta-(1,2,3-triazol-1-yl) methylpenam-3alpha-carboxylic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59248985A JPS61126087A (en) | 1984-11-26 | 1984-11-26 | Production of 2alpha-methyl-2beta-(1,2,3-triazol-1-yl) methylpenam-3alpha-carboxylic acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61126087A true JPS61126087A (en) | 1986-06-13 |
Family
ID=17186309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59248985A Pending JPS61126087A (en) | 1984-11-26 | 1984-11-26 | Production of 2alpha-methyl-2beta-(1,2,3-triazol-1-yl) methylpenam-3alpha-carboxylic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61126087A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4958020A (en) * | 1989-05-12 | 1990-09-18 | American Cyanamid Company | Process for producing β-lactamase inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58225091A (en) * | 1982-06-21 | 1983-12-27 | Taiho Yakuhin Kogyo Kk | Penicillin derivative and its preparation |
| JPS59118790A (en) * | 1982-12-24 | 1984-07-09 | Taiho Yakuhin Kogyo Kk | Penicillin derivative and its preparation |
-
1984
- 1984-11-26 JP JP59248985A patent/JPS61126087A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58225091A (en) * | 1982-06-21 | 1983-12-27 | Taiho Yakuhin Kogyo Kk | Penicillin derivative and its preparation |
| JPS59118790A (en) * | 1982-12-24 | 1984-07-09 | Taiho Yakuhin Kogyo Kk | Penicillin derivative and its preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4958020A (en) * | 1989-05-12 | 1990-09-18 | American Cyanamid Company | Process for producing β-lactamase inhibitor |
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