JP2603638B2 - Analysis and preparative methods for optical isomers - Google Patents
Analysis and preparative methods for optical isomersInfo
- Publication number
- JP2603638B2 JP2603638B2 JP62170376A JP17037687A JP2603638B2 JP 2603638 B2 JP2603638 B2 JP 2603638B2 JP 62170376 A JP62170376 A JP 62170376A JP 17037687 A JP17037687 A JP 17037687A JP 2603638 B2 JP2603638 B2 JP 2603638B2
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- pyridonecarboxylic acid
- atom
- acid compound
- alkyl group
- 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 - Lifetime
Links
- 238000004458 analytical method Methods 0.000 title claims description 7
- 230000003287 optical effect Effects 0.000 title description 8
- 238000002360 preparation method Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims description 17
- -1 pyridonecarboxylic acid compound Chemical class 0.000 claims description 12
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910001431 copper ion Inorganic materials 0.000 claims description 5
- 229910021645 metal ion Inorganic materials 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 8
- 125000004122 cyclic group Chemical group 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 125000003277 amino group Chemical group 0.000 claims 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 5
- YSLIPUSJNFIFAB-UHFFFAOYSA-N 2-oxopyridine-1-carboxylic acid Chemical class OC(=O)N1C=CC=CC1=O YSLIPUSJNFIFAB-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 229930182844 L-isoleucine Natural products 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- SCIFESDRCALIIM-UHFFFAOYSA-N N-Me-Phenylalanine Natural products CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 description 1
- SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【発明の詳細な説明】 〈産業上の利用分野〉 本発明は不斉炭素を有する（±）−ピリドンカルボン
酸系化合物の光学異性体分析と光学分割に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to optical isomer analysis and optical resolution of (±) -pyridonecarboxylic acid compounds having an asymmetric carbon.
ピリドンカルボン酸系化合物は合成抗菌薬として広く
用いられている。これらのうち不斉炭素を持つ誘導体
で、立体異性体となる化合物間でより有用性の高い異性
体が見い出された場合、これらの分析法及び分取精製法
を確立することは重要である。Pyridonecarboxylic acid compounds are widely used as synthetic antibacterial agents. In the case where a derivative having an asymmetric carbon is found to have a more useful isomer among the compounds which are stereoisomers, it is important to establish an analytical method and a preparative purification method.
〈従来の技術〉 光学活性ピリドンカルボン酸系化合物の光学純度を評
価する方法としては旋光度を用いる他には直接的な方法
は見当たらない。間接的な方法としては適当なジアステ
レオマー誘導体に化学修飾して分離分析する方法がある
が、操作が繁雑となり簡便な分析法とは言えない。また
特殊な光学活性体分離用の高速液体クロマトグラフィー
（以下、HPLCと略す）用カラムを用いて分析する方法も
存在するが、この様なクロマトカラムは一般に高価で一
般性に欠ける。一方HPLCの場合、移動相にアミノ酸及び
銅イオンを添加し配位子の交換を原理として利用した方
法はアミノ酸及びアミノ酸誘導体の分析には適用されて
いるがピリドンカルボン酸には応用されていない。<Conventional Technology> As a method for evaluating the optical purity of an optically active pyridonecarboxylic acid-based compound, no direct method other than the use of optical rotation has been found. As an indirect method, there is a method in which an appropriate diastereomer derivative is chemically modified and separated and analyzed. However, the operation is complicated and cannot be said to be a simple analysis method. There is also a method of performing analysis using a column for high-performance liquid chromatography (hereinafter abbreviated as HPLC) for separating a special optically active substance, but such a chromatographic column is generally expensive and lacks generality. On the other hand, in the case of HPLC, a method in which amino acids and copper ions are added to a mobile phase and ligand exchange is used in principle has been applied to the analysis of amino acids and amino acid derivatives, but not to pyridonecarboxylic acids.
〈本発明の目的〉 本発明は光学活性なピリドンカルボン酸系化合物の光
学純度を高精度かつ高感度に分析する方法であり、分取
精製を行なうことにより、工業的にも優れた光学分割法
を提供するものである。<Object of the present invention> The present invention is a method for analyzing the optical purity of an optically active pyridone carboxylic acid compound with high accuracy and high sensitivity. Is provided.
本発明者らは前記目的をを達成するべく鋭意研究の結
果、２価の銅イオンの共存下に工業的に大量にかつ安価
に入手できる光学活性アミノ酸を配位子として移動相に
添加すると、ピリドンカルボン酸系化合物の光学対掌体
が一般的な担体のクロマトカラムを用いたHPLCで直接的
にかつ容易に分離され、さらにこれらは蛍光検出または
紫外部吸収検出により検出されることを見いだした。こ
の知見に基いて本発明を完成した。The present inventors have conducted intensive studies in order to achieve the above object, and as a result of adding an optically active amino acid which is industrially available in a large amount and inexpensively as a ligand to a mobile phase in the presence of divalent copper ions, We have found that the enantiomers of pyridonecarboxylic acid compounds can be directly and easily separated by HPLC using a common carrier chromatography column, and that they can be detected by fluorescence detection or ultraviolet absorption detection. . The present invention has been completed based on this finding.
〈本発明の構成〉 本発明の要旨は不斉炭素を持つピリドンカルボン酸系
化合物の光学異性体を分析又は分取するためにHPLCを用
い、このHPLCの移動相に配位子として光学活性なアミノ
酸を２価の金属イオン、好ましくは銅イオンと共に添加
し、一般の逆相分配系カラムを用いて分離するものであ
る。ピリドンカルボン酸系化合物は、300nm付近に紫外
部の吸収極大を、また370nm付近に励起極大そして505nm
付近に蛍光極大を示す為、紫外部吸収検出器または蛍光
検出器を前記の各々の条件に設定することにより選択的
かつ高感度に検出できるものである。<Constitution of the present invention> The gist of the present invention is to use HPLC to analyze or fractionate the optical isomer of a pyridonecarboxylic acid compound having an asymmetric carbon, and to have an optically active ligand as a ligand in the mobile phase of this HPLC. Amino acids are added together with divalent metal ions, preferably copper ions, and separated using a general reversed-phase partition column. Pyridonecarboxylic acid compounds have an ultraviolet absorption maximum near 300 nm, an excitation maximum near 370 nm and 505 nm.
Since a fluorescence maximum is shown in the vicinity, detection can be performed selectively and with high sensitivity by setting an ultraviolet absorption detector or a fluorescence detector to each of the above conditions.
またこのHPLC操作では、各々のピリドンカルボン酸系
化合物が適当な保持時間の後に溶出されるように移動相
として適当な有機溶媒の種類と濃度を選択する必要があ
るが、本法では低級アルコール−水系混合物、好ましく
はメタノール−水系混合物を使用することが推奨され
る。In this HPLC operation, it is necessary to select an appropriate type and concentration of an organic solvent as a mobile phase so that each pyridonecarboxylic acid compound is eluted after an appropriate retention time. It is recommended to use an aqueous mixture, preferably a methanol-water mixture.
本発明に従えば試料の誘導体化操作なしに試料を直接
HPLC手法にて分離でき紫外線部吸収又は蛍光を測定する
ことにより微量に混入する光学異性体を検出、定量する
ことが可能になったものである。According to the present invention, the sample can be directly
It is possible to detect and quantitate a small amount of optical isomers that can be separated by an HPLC method and can be traced by measuring ultraviolet absorption or fluorescence.
以下、本発明の構成と効果を実施例により具体的に説
明するか、本発明はこの実施例にのみ限定されるもので
はない。Hereinafter, the configuration and effects of the present invention will be specifically described with reference to examples, or the present invention is not limited to these examples.
実施例1.各種アミノ酸添加で得られる分離係数 （±）−９−フルオロ−2,3−ジヒドロ−３−メチル
−10−（４−メチル−１−ペプラジニル）−７−オキソ
−7H−ピリド［1,2,3−de］［1,4］ベンゾオキサジン−
６−カルボン酸（化合物１）の0.5mg/mlメタノール溶液
のｎμｌを下記条件下のHPLCに直接注入し、得られた分
離係数αの結果を第１表に示す。Example 1. Separation coefficient obtained by addition of various amino acids (±) -9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-peprazinyl) -7-oxo-7H-pyrido [ 1,2,3-de] [1,4] benzoxazine-
N μl of a 0.5 mg / ml methanol solution of 6-carboxylic acid (compound 1) was directly injected into the HPLC under the following conditions, and the results of the obtained separation coefficient α are shown in Table 1.
カラム：オクタデシルシリカゲル充填カラム（ODSカラ
ム）150mm×6mmi.d. 移動相：アミノ酸＋硫酸銅（アミノ酸の1/2モル）水溶
液／メタノール＝85/15 流速:60ml/h 温度：室温 検出器：紫外部分光光度計、300nm 蛍光光度計、励起波長370nm 蛍光波長505nm 表1.各種アミノ酸での分離係数（α） アミノ酸 添加濃度 α Ｌ−フェニルアラニン 6mM 1.23 Ｌ−イソロイシン 6mM 1.22 Ｌ−ロイシン 6mM 1.16 アスパルテーム 2mM 1.14 Ｎ−メチル−Ｌ−フェニルアラニン 2mM 1.13 Ｌ−バリン 6mM 1.10 Ｌ−トリプトファン 6mM 1.07 Ｌ−メチオニン 6mM 1.04 Ｌ−チロシン 6mM 1.06 実施例2.ピリドンカルボン酸系化合物の分離例 移動相添加配位子としてＬ−フェニルアラニンを用い
前記の条件で分離を試みたところ表２に示す構造の化合
物で分離が達成された。また、得られたクロマトグラム
のピークの保持時間は、別途に合成済の標品の保持時間
と一致している。Column: Octadecyl silica gel packed column (ODS column) 150 mm x 6 mm i.d. Mobile phase: amino acid + copper sulfate (1/2 mol of amino acid) aqueous solution / methanol = 85/15 Flow rate: 60 ml / h Temperature: room temperature Detector: ultraviolet Partial photometer, 300nm Fluorometer, Excitation wavelength 370nm Fluorescence wavelength 505nm Table 1. Separation coefficient of various amino acids (α) Amino acid addition concentration α L-phenylalanine 6mM 1.23 L-isoleucine 6mM 1.22 L-leucine 6mM 1.16 Aspartame 2mM 1.14 N-methyl-L-phenylalanine 2 mM 1.13 L-valine 6 mM 1.10 L-tryptophan 6 mM 1.07 L-methionine 6 mM 1.04 L-tyrosine 6 mM 1.06 Example 2. Example of separation of pyridone carboxylic acid compound L- as a mobile phase-added ligand When separation was attempted using phenylalanine under the above conditions, separation was achieved with compounds having the structures shown in Table 2. The retention time of the obtained chromatogram peak coincides with the retention time of a separately synthesized sample.
この様に本発明は不斉炭素を持つピリドンカルボン酸
系化合物に対し、直接的な、簡便で迅速、且つ、精度の
良い分析法及び分取精製法である。 As described above, the present invention is a direct, simple, rapid, and accurate analytical and preparative purification method for a pyridonecarboxylic acid compound having an asymmetric carbon.
図面はクロマトグラムの一例である。 The drawing is an example of a chromatogram.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｇ０１Ｎ 30/26 Ｇ０１Ｎ 30/26 Ａ ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 6 Identification code Agency reference number FI Technical display location G01N 30/26 G01N 30/26 A
Claims (8)
合物を光学活性アミノ酸及び２価の金属イオンの存在下
に高速液体クロマトグラフィーにより直接分離すること
を特徴とする（±）−ピリドンカルボン酸系化合物の分
析法。1. A (±) -pyridonecarboxylic acid compound which is directly separated from a pyridonecarboxylic acid compound having an asymmetric carbon by high performance liquid chromatography in the presence of an optically active amino acid and a divalent metal ion. Compound analysis method.
求の範囲第１項記載の（±）−ピリドンカルボン酸系化
合物の分析法。2. The method for analyzing (±) -pyridonecarboxylic acid compounds according to claim 1, wherein copper ions are used as metal ions.
般式［Ｉ］ （式中、ＸおよびＹは、各々独立して、水素原子または
ハロゲン原子を表し、Ｚは水素原子もしくはハロゲン原
子または環状アミノ基を表し、Ａは酸素原子もしくは硫
黄原子または、水素原子あるいは低級アルキル基で置換
された窒素原子あるいはメチレン基、エテニレン基ある
いはケト基を表わし、R1は低級アルキル基またはハロゲ
ン化低級アルキル基を表し、ｎは整数の０、１または２
である。）で示されるピリドンカルボン酸系化合物であ
る特許請求の範囲第２項記載の（±）−ピリドンカルボ
ン酸系化合物の分析法。3. The (±) -pyridonecarboxylic acid compound of the general formula [I] (Wherein X and Y each independently represent a hydrogen atom or a halogen atom, Z represents a hydrogen atom or a halogen atom or a cyclic amino group, A represents an oxygen atom or a sulfur atom, or a hydrogen atom or a lower alkyl R 1 represents a lower alkyl group or a halogenated lower alkyl group; and n represents an integer of 0, 1 or 2;
It is. 3. The method for analyzing (±) -pyridonecarboxylic acid compounds according to claim 2, which is a pyridonecarboxylic acid compound represented by the formula:
般式［II］ （式中、ＸおよびＹは、各々独立して、水素原子または
ハロゲン原子を表し、Ｚは一般式［III］ または一般式［IV］ で示される環状アミノ基を表し、ここでR3、R4、R5およ
びR6は水素原子または低級アルキル基を表し、R7は低級
アルキル基を表し、ｋは０または１であり、ｌ、ｍ、ｐ
およびｑは、各々独立して、整数の０、１または２であ
り、R2は直鎖状または環状の低級アルキル基またはハロ
ゲン化低級アルキル基を表し、Ａは、窒素原子もしく
は、水素原子またはハロゲン原子で置換された炭素原子
を表す。）で示されるピリドンカルボン酸系化合物であ
る特許請求の範囲第２項記載の（±）−ピリドンカルボ
ン酸系化合物の分析法。4. The (±) -pyridonecarboxylic acid compound of the general formula [II] (Wherein, X and Y each independently represent a hydrogen atom or a halogen atom, and Z represents a general formula [III] Or the general formula [IV] Wherein R 3 , R 4 , R 5 and R 6 represent a hydrogen atom or a lower alkyl group; R 7 represents a lower alkyl group; k is 0 or 1; , M, p
And q are each independently an integer of 0, 1 or 2, R 2 represents a linear or cyclic lower alkyl group or a halogenated lower alkyl group, and A represents a nitrogen atom, a hydrogen atom or Represents a carbon atom substituted with a halogen atom. 3. The method for analyzing (±) -pyridonecarboxylic acid compounds according to claim 2, which is a pyridonecarboxylic acid compound represented by the formula:
合物を光学活性アミノ酸及び２価の金属イオンの存在下
に高速液体クロマトグラフィーにより直接分離すること
を特徴とする（±）−ピリドンカルボン酸系化合物の分
取精製法。5. A (±) -pyridonecarboxylic acid compound which is directly separated by high performance liquid chromatography in the presence of an optically active amino acid and a divalent metal ion from a pyridonecarboxylic acid compound having an asymmetric carbon. A method for preparative purification of compounds.
求の範囲第５項記載の（±）−ピリドンカルボン酸系化
合物の分取精製法。6. The method for fractionating and purifying (±) -pyridonecarboxylic acid compounds according to claim 5, wherein copper ions are used as metal ions.
般式［Ｉ］ （式中、ＸおよびＹは、各々独立して、水素原子または
ハロゲン原子を表し、Ｚは水素原子もしくはハロゲン原
子または環状アミノ基を表し、Ａは酸素原子もしくは硫
黄原子または、水素原子あるいは低級アルキル基で置換
された窒素原子あるいはメチレン基、エテニレン基ある
いはケト基を表し、R1は低級アルキル基またはハロゲン
化低級アルキル基を表し、ｎは整数の０、１または２で
ある。）で示されるピリドンカルボン酸系化合物である
特許請求の範囲第６項記載の（±）−ピリドンカルボン
酸系化合物の分取精製法。7. The (±) -pyridonecarboxylic acid compound represented by the general formula [I] (Wherein, X and Y each independently represent a hydrogen atom or a halogen atom, Z represents a hydrogen atom or a halogen atom or a cyclic amino group, A represents an oxygen atom or a sulfur atom, or a hydrogen atom or a lower alkyl Represents a nitrogen atom or a methylene group, an ethenylene group or a keto group substituted by a group, R 1 represents a lower alkyl group or a halogenated lower alkyl group, and n is an integer of 0, 1 or 2.) The method for preparative purification of (±) -pyridonecarboxylic acid compound according to claim 6, which is a pyridonecarboxylic acid compound.
般式［II］ （式中、ＸおよびＹは、各々独立して、水素原子または
ハロゲン原子を表し、Ｚは一般式［III］ または一般式［IV］ で示される環状アミノ基を表し、ここでR3、R4、R5およ
びR6は水素原子または低級アルキル基を表し、R7は低級
アルキル基を表し、ｋは０または１であり、ｌ、ｍ、ｐ
およびｑは、各々独立して、整数の０、１または２であ
り、R2は直鎖状または環状の低級アルキル基またはハロ
ゲン化低級アルキル基を表し、Ａは、窒素原子もしく
は、水素原子またはハロゲン原子で置換された炭素原子
を表す。） で示されるピリドンカルボン酸系化合物である特許請求
の範囲第６項記載の（±）−ピリドンカルボン酸系化合
物の分取精製法。8. The (±) -pyridonecarboxylic acid compound of the general formula [II] (Wherein, X and Y each independently represent a hydrogen atom or a halogen atom, and Z represents a general formula [III] Or the general formula [IV] Wherein R 3 , R 4 , R 5 and R 6 represent a hydrogen atom or a lower alkyl group; R 7 represents a lower alkyl group; k is 0 or 1; , M, p
And q are each independently an integer of 0, 1 or 2, R 2 represents a linear or cyclic lower alkyl group or a halogenated lower alkyl group, and A represents a nitrogen atom, a hydrogen atom or Represents a carbon atom substituted with a halogen atom. 7. The method for preparative purification of (±) -pyridonecarboxylic acid compounds according to claim 6, which is a pyridonecarboxylic acid compound represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62170376A JP2603638B2 (en) | 1987-07-08 | 1987-07-08 | Analysis and preparative methods for optical isomers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62170376A JP2603638B2 (en) | 1987-07-08 | 1987-07-08 | Analysis and preparative methods for optical isomers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6413455A JPS6413455A (en) | 1989-01-18 |
| JP2603638B2 true JP2603638B2 (en) | 1997-04-23 |
Family
ID=15903792
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62170376A Expired - Lifetime JP2603638B2 (en) | 1987-07-08 | 1987-07-08 | Analysis and preparative methods for optical isomers |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2603638B2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009198177A (en) * | 2006-06-02 | 2009-09-03 | Dai Ichi Seiyaku Co Ltd | Separation method |
| JP5052238B2 (en) * | 2007-07-17 | 2012-10-17 | 三菱電機株式会社 | Remote controller for hot water storage system |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61243081A (en) * | 1985-04-19 | 1986-10-29 | Dainippon Pharmaceut Co Ltd | Pyridonecarboxylic acid derivative, and ester and salt thereof |
| JPH0635458B2 (en) * | 1985-02-15 | 1994-05-11 | 大日本製薬株式会社 | Pyridonecarboxylic acid derivatives, their esters and their salts |
| JPH0635457B2 (en) * | 1985-06-28 | 1994-05-11 | 杏林製薬株式会社 | Pyridonecarboxylic acid derivative and method for producing the same |
| JPH0696572B2 (en) * | 1985-07-17 | 1994-11-30 | 大日本製薬株式会社 | Pyridonecarboxylic acid derivatives, their esters and their salts |
| JPS6236383A (en) * | 1985-08-08 | 1987-02-17 | Dainippon Pharmaceut Co Ltd | Pyridonecarboxylic acid derivative |
| JPH0615526B2 (en) * | 1985-09-27 | 1994-03-02 | 大日本製薬株式会社 | 3-Aminomethylpyrrolidine derivative and its salt |
-
1987
- 1987-07-08 JP JP62170376A patent/JP2603638B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6413455A (en) | 1989-01-18 |
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