KR19990075668A - Chiral stationary phase and LC-filled chiral column for LC for optical division of racemic compounds having a primary amino group - Google Patents
Chiral stationary phase and LC-filled chiral column for LC for optical division of racemic compounds having a primary amino group Download PDFInfo
- Publication number
- KR19990075668A KR19990075668A KR1019980009996A KR19980009996A KR19990075668A KR 19990075668 A KR19990075668 A KR 19990075668A KR 1019980009996 A KR1019980009996 A KR 1019980009996A KR 19980009996 A KR19980009996 A KR 19980009996A KR 19990075668 A KR19990075668 A KR 19990075668A
- Authority
- KR
- South Korea
- Prior art keywords
- crown
- optically active
- chiral
- tetracarboxylic acid
- csp
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
Abstract
본 발명은 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 1 [(2R,3R,11R,12R)-1,4,7,10,13,16-hexaoxacyclooctadecane-2,3,11,12-The present invention relates to optically active (18-crown-6) -2,3,11,12-tetracarboxylic acid 1 [(2R, 3R, 11R, 12R) -1,4,7,10,13,16-hexaoxacyclooctadecane- 2,3,11,12-
tetracarboxylic acid] 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 2 [(4R,5R,15R,16R)-3,6,14,17-tetraoxa-23,24-tetracarboxylic acid] or optically active bispyridino- (18-crown-6) tetracarboxylic acid 2 [(4R, 5R, 15R, 16R) -3,6,14,17-tetraoxa-23,24-
diazatricyclo[17,3,1,18,12]tetracosa-1(23),8,10,12(24),19,21-hexaene-4,5,15,16-tetracarboxylic acid]를 LC 용 실리카 젤에 공유 결합시킨 키랄고정상들(CSP 3 및 CSP 4)과 이들로 충진된 LC 용 키랄 칼럼에 관한 것으로, 일차 아미노기를 가지는 라세미 화합물들을 구성하는 두 광학이성질체를 분리하는 광학분할방법을 제공하고자 하는 것인 바,diazatricyclo [17,3,1,1 8,12 ] tetracosa-1 (23), 8,10,12 (24), 19,21-hexaene-4,5,15,16-tetracarboxylic acid] silica for LC The present invention relates to a chiral stationary phase (CSP 3 and CSP 4) covalently bonded to a gel and a chiral column for LC filled therewith, to provide an optical splitting method for separating two optical isomers constituting racemic compounds having a primary amino group. That is,
본 발명은 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 1 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 2를 아세트산 무수물과 반응시켜 제조된 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 무수물 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 무수물을 아미노프로필 실리카 젤 혹은 머캅토프로필 실리카 젤과 반응시켜 제조된 도 1과 같은 키랄고정상들(CSP 3 및 CSP 4)과 이들 키랄고정상들로 충진된 LC 용 키랄칼럼들로 된 것에 요지가 있다.The present invention is prepared by reacting optically active (18-crown-6) -2,3,11,12-tetracarboxylic acid 1 or optically active bispyridino- (18-crown-6) tetracarboxylic acid 2 with acetic anhydride. Optically active (18-crown-6) -2,3,11,12-tetracarboxylic anhydride or optically active bispyridino- (18-crown-6) tetracarboxylic anhydride to aminopropyl silica gel or mercaptopropyl There is a summary of chiral stationary phases (CSP 3 and CSP 4) as shown in FIG. 1 prepared by reaction with silica gel and chiral columns for LC filled with these chiral stationary phases.
Description
본 발명은 퀴놀론계 항생제, 아미노 알코올, 아미노산 등과 같이 일차 아미노기를 가지고 있는 라세미 화합물(라세미 의약품 포함)들을 구성하는 두 개의 광학이성질체를 분리하는데 사용할 수 있는 LC 용 키랄고정상들과 이 키랄고정상들로 충진된 키랄칼럼의 제조에 관한 것이다.The present invention relates to chiral stationary phases and chiral stationary phases for LCs which can be used to separate two optical isomers that constitute racemic compounds (including racemic drugs) having primary amino groups such as quinolone antibiotics, amino alcohols, amino acids, etc. It relates to the production of chiral column filled with.
생리활성을 나타내는 많은 의약품들이 광학활성일 뿐만 아니라 서로 다른 절대배열을 가진 의약품들이 인체내에서 서로 다른 약리작용을 나타내는 예들이 많이 알려짐에 따라 라세미 의약품들을 구성하는 두 개의 광학 이성질체를 분리하고 광학활성 의약품들의 광학순도를 측정할 수 있는 LC 용 키랄 고정상 및 키랄칼럼에 대한 관심은 화학, 의학, 약학 등의 분야에서 점점 더 커지고 있다.Many drugs that exhibit physiological activity are not only optically active but also have different pharmacological effects in humans with different absolute arrangements. As a result, the two optical isomers that constitute racemic drugs are separated and optically active. The interest in chiral stationary phases and chiral columns for LCs, which can measure the optical purity of medicines, is increasing in the fields of chemistry, medicine and pharmacy.
많은 키랄 의약품들이 일차 아미노기를 가지고 있기 때문에 일차 아미노기를 가지는 키랄 화합물들의 두 광학이성질체를 쉽게 광학분할하고 또 광학순도를 손쉽게 측정할 수 있는 LC 용 키랄고정상과 이 키랄고정상으로 충진된 키랄칼럼은 키랄 의약품을 개발하고 연구하는데 유용하게 쓰일 수 있다.Since many chiral drugs have a primary amino group, the chiral stationary phase for LC and chiral column filled with the chiral stationary phase can be easily split into two optical isomers of chiral compounds having a primary amino group and the optical purity can be easily measured. It can be useful for developing and researching.
이에 본 발명은 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 1 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 2를 적절한 방법으로 실리카 젤에 공유결합시켜 일차 아미노기를 가지는 라세미 의약품 등의 광학분할에 유용하게 사용할 수 있는 LC 용 키랄고정상을 제조하고 제조된 키랄고정상을 LC 용 공 칼럼에 충진시켜 LC 용 키랄칼럼을 제조하고자 하는 것이다.Accordingly, the present invention provides an optically active (18-crown-6) -2,3,11,12-tetracarboxylic acid 1 or an optically active bispyridino- (18-crown-6) tetracarboxylic acid 2 in an appropriate manner. It is intended to produce a chiral column for LC by covalently binding to prepare a chiral stationary phase for LC that can be usefully used for optical separation of racemic drugs, etc. having a primary amino group, and filling the prepared chiral stationary phase in the LC column.
도 1은 본 발명 CSP3 및 CSP4의 화학적 구조도1 is a chemical structural diagram of the present invention CSP3 and CSP4
1. 키랄고정상의 제조 방법1. Manufacturing method of chiral stationary phase
LC 용 키랄고정상은 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 1 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 2를 아세트산 무수물과 반응시켜 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산의 무수물 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산의 무수물을 제조하고 이것을 아미노프로필 실리카 젤 혹은 머캅토프로필 실리카 젤과 반응시켜 제조된다.The chiral stationary phase for LCs reacts optically active (18-crown-6) -2,3,11,12-tetracarboxylic acid 1 or optically active bispyridino- (18-crown-6) tetracarboxylic acid 2 with acetic anhydride. To prepare an optically active anhydride of (18-crown-6) -2,3,11,12-tetracarboxylic acid or an anhydride of optically active bispyridino- (18-crown-6) tetracarboxylic acid, which was then subjected to aminopropyl silica. Prepared by reaction with gel or mercaptopropyl silica gel.
구체적인 방법은 아래와 같다.The specific method is as follows.
100 ㎖의 플라스크에 300 mg의 광학활성인 (18-크라운-6)-2,3,11,12-테트라카르복시산 1 혹은 광학활성인 비스피리디노-(18-크라운-6) 테트라카르복시산 2와 30 ㎖의 정제한 염화 아세틸을 넣고 아르곤 기류하에서 24 시간 동안 환류한다.In a 100 ml flask, 300 mg of optically active (18-crown-6) -2,3,11,12-tetracarboxylic acid 1 or optically active bispyridino- (18-crown-6) tetracarboxylic acid 2 and 30 Add ml of purified acetyl chloride and reflux for 24 hours under argon stream.
용액이 투명하게 됨을 확인한 후 반응을 멈추고 감압하여 용매를 완전히 제거하면 흰색 고체인 광학활성 (18-크라운-6)-2,3,11,12-테트라카르복시산 무수물 혹은 광학활성 비스피리디노-(18-크라운-6) 테트라카르복시산 무수물이 얻어진다.After confirming that the solution became clear, the reaction was stopped and reduced pressure was used to completely remove the solvent. The white solid was optically active (18-crown-6) -2,3,11,12-tetracarboxylic anhydride or optically active bispyridino- (18 -Crown-6) tetracarboxylic anhydride is obtained.
이와 동시에 2.8 g의 아미노프로필 실리카 젤 (혹은 머캅토프로필 실리카 젤)을 Dean-Stark trap이 장치된 250 ㎖의 이구 둥근바닥 플라스크에 가하고 여기에 정제된 벤젠 100 ㎖를 가하여 2 시간 동안 환류함으로서 아미노프로필 실리카 젤 (혹은 머캅토프로필 실리카 젤)에 흡착되어 있는 수분을 완전히 제거한다.At the same time 2.8 g of aminopropyl silica gel (or mercaptopropyl silica gel) was added to a 250 ml two-necked round bottom flask equipped with Dean-Stark trap, and 100 ml of purified benzene was added thereto and refluxed for 2 hours. Completely remove the moisture adsorbed on the silica gel (or mercaptopropyl silica gel).
상기 수분이 완전히 제거된 아미노프로필 실리카 젤 (혹은 머캅토프로필 실리카 젤)이 부유되어 있는 용액의 벤젠을 감압 증발기를 사용하여 제거한다.Benzene of the solution suspended in the aminopropyl silica gel (or mercaptopropyl silica gel) from which the moisture is completely removed is removed using a reduced pressure evaporator.
여기에 정제한 디클로로메탄 20 ㎖와 트리에틸아민 0.23 ㎖를 가하고 반응 용기의 온도를 0 ℃로 낮춘다.20 ml of purified dichloromethane and 0.23 ml of triethylamine were added thereto, and the temperature of the reaction vessel was lowered to 0 ° C.
여기에 10 ㎖의 정제한 디클로로메탄에 용해된 위에서 합성한 광학활성 (18-크라운-6)-2,3,11,12-테트라카르복시산 무수물 혹은 광학활성 비스피리디노-(18-크라운-6) 테트라카르복시산 무수물을 저어주면서 천천히 가한 후 전체 반응 혼합물을 상온에서 2 일동안 저어준다.The above-described optically active (18-crown-6) -2,3,11,12-tetracarboxylic anhydride or optically active bispyridino- (18-crown-6) dissolved in 10 ml of purified dichloromethane. Stir slowly with tetracarboxylic anhydride and stir the whole reaction mixture for 2 days at room temperature.
이 과정에서 모든 반응은 아르곤 기류하에서 실시한다.In this process all reactions are carried out under an argon stream.
합성된 변형 실리카 젤은 유리 여과기를 이용하여 메탄올, 디클로로메탄, 아세트산 에틸, 헥산의 순으로 씻고 건조하여 키랄고정상 CSP 3 혹은 CSP 4를 얻는다.The synthesized modified silica gel was washed in the order of methanol, dichloromethane, ethyl acetate, hexane and dried using a glass filter to obtain a chiral stationary CSP 3 or CSP 4.
상기 키랄고정상의 제조방법과 관련된 화합물 1과 2의 구조 및 합성된 키랄고정상들(CSP 3 및 CSP 4)의 구조와 관련된 화학식 1은 다음과 같다.Formula 1 related to the structure of the compounds 1 and 2 and the structure of the synthesized chiral stationary phases (CSP 3 and CSP 4) associated with the chiral stationary phase production method is as follows.
2. 키랄 칼럼의 제조2. Preparation of Chiral Column
상기에서 합성한 키랄고정상 CSP 3 혹은 CSP 4를 메탄올에 부유시키고 슬러리 충진기를 이용하여 HPLC 용 스텐레스강 공 칼럼에 충진하여 키랄 칼럼을 제조한다.The chiral fixed-phase CSP 3 or CSP 4 synthesized above was suspended in methanol and packed in a stainless steel empty column for HPLC using a slurry filler to prepare a chiral column.
3. 광학분할의 실시예3. Example of Optical Splitting
본 발명에서 그 제조 방법이 알려진 키랄고정상을 HPLC 용 공 칼럼에 충진하여 제조된 키랄 칼럼을 라세미 화합물의 광학분할에 응용한 실시예는 아래와 같다.In the present invention, an example in which a chiral column prepared by filling a hollow column for HPLC with a known chiral method is applied to optical division of a racemic compound is as follows.
실시예Example
퀴놀론계 항생제로 쓰일 수 있는 화합물과 라세미 아미노산 및 기타 일차 아미노기를 가지고 있는 라세미 화합물들을 키랄고정상, CSP 3(X=NH)이 충진된 키랄 칼럼상에서 광학분할하였을 때 광학분할의 예는 다음의 표 1과 같다.Examples of the optical splitting of a compound which can be used as a quinolone antibiotic and a racemic compound having racemic amino acids and other primary amino groups on a chiral stationary, chiral column filled with CSP 3 (X = NH) are as follows. Table 1 is as follows.
k1, k2는 capacity factor, a는 Separation factor, RS는 Resolution factor 임.k 1 , k 2 are capacity factor, a is Separation factor, and R S is Resolution factor.
조건 A : 용매=80 % CH3OH in H2O + 10 mM H2SO4(pH=1.6), 온도=20℃, 유속=1.2㎖/min.Condition A: solvent = 80% CH 3 OH in H 2 O + 10 mM H 2 SO 4 (pH = 1.6), temperature = 20 ° C., flow rate = 1.2 ml / min.
조건 B : 용매=15 % CH3OH + 0.1 % HClO4in H2O (pH=1.5), 온도=18℃, 유속=0.5㎖/min. 조건 C : 용매=80 % CH3OH in H2O + 10 mM HClO4(pH=2.0), 온도=20℃, 유속=0.5㎖/min.Condition B: solvent = 15% CH 3 OH + 0.1% HClO 4 in H 2 O (pH = 1.5), temperature = 18 ° C., flow rate = 0.5 ml / min. Condition C: solvent = 80% CH 3 OH in H 2 O + 10 mM HClO 4 (pH = 2.0), temperature = 20 ° C., flow rate = 0.5 ml / min.
이상의 본 발명은 전술한 실시예에서 살펴본 바와 같이 본 발명에서 제조된 키랄고정상으로 충진된 키랄컬럼들은 일차 아미노기를 가지고 있는 라세미 화합물들의 두 광학이성질체를 아주 효과적으로 광학분할함을 알 수 있으며 이러한 화합물들의 광학분할에 유용하게 응용될 수 있을 것으로 기대되는 것으로, 일차 아미노기를 가지는 키랄 화합물들의 두 광학이성질체를 쉽게 광학분할하고 또 광학순도를 쉽게 측정할 수 있게 되어 키랄 의약품을 개발하고 연구하는 데 유용하게 이용될 수 있는 등의 여러 잇점과 효과를 제공하는 것이다.As described in the above-described embodiment, the chiral column-filled chiral columns prepared in the present invention can be seen that the optical splitting of two optical isomers of racemic compounds having a primary amino group is very effective. It is expected to be useful for optical splitting, and it is easy to optically split two optical isomers of chiral compounds having a primary amino group and to measure optical purity, which is useful for developing and studying chiral medicines. It offers many benefits and benefits, such as possible.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019980009996A KR100263872B1 (en) | 1998-03-12 | 1998-03-12 | Liquid chromatographic chiral stationary phases and chiral columns for the resolution of racemic compounds containing primary amino group |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019980009996A KR100263872B1 (en) | 1998-03-12 | 1998-03-12 | Liquid chromatographic chiral stationary phases and chiral columns for the resolution of racemic compounds containing primary amino group |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR19990075668A true KR19990075668A (en) | 1999-10-15 |
| KR100263872B1 KR100263872B1 (en) | 2000-08-16 |
Family
ID=19535244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019980009996A KR100263872B1 (en) | 1998-03-12 | 1998-03-12 | Liquid chromatographic chiral stationary phases and chiral columns for the resolution of racemic compounds containing primary amino group |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100263872B1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030077238A (en) * | 2002-03-25 | 2003-10-01 | 대한민국(부산대학교 총장) | Liquid chromatographic ligand exchange chiral stationary phases, chiral columns packed with the ligand exchange chiral stationary phases |
| KR20040021467A (en) * | 2002-09-04 | 2004-03-10 | 대한민국(부산대학교 총장) | Improved Crown Ether Chiral Statioary Phases and Chiral Columns for the Liquid Chromatographic Resolution of Chiral Drugs |
| KR100454712B1 (en) * | 2001-08-03 | 2004-11-05 | 한국과학기술연구원 | Chiral stationary phases, chiral columns with the chiral stationary phases and process for producing the chiral stationary phases |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100364255B1 (en) * | 2000-09-08 | 2002-12-12 | 현명호 | Crown Ether Chiral Stationary Phase and Chiral Column for the Liquid Chromatographic Resolution of Biologically Active Racemic Primary Amino Compounds |
| KR100387932B1 (en) * | 2000-11-09 | 2003-06-18 | 현명호 | Crown Ether Chiral Statioary Phases and Chiral Columns for the Liquid Chromatographic Resolution of Chiral Drugs |
| KR100520998B1 (en) * | 2002-10-07 | 2005-10-13 | 부산대학교 산학협력단 | Liquid Chromatographic Crown Ether Chiral Statioary Phases with Double Tethering Groups and Chiral Columns Packed with Them |
| KR100528959B1 (en) | 2003-02-11 | 2005-11-16 | 학교법인 포항공과대학교 | Silica gel bonded with cucurbiturils |
| KR100988321B1 (en) | 2003-07-26 | 2010-10-18 | 포항공과대학교 산학협력단 | Polymer comprising cucurbiturils, stationary phase and column using the same |
| WO2007046575A1 (en) | 2005-10-20 | 2007-04-26 | Postech Academy-Industry Foundation | The application using non-covalent bond between a cucurbituril derivative and a ligand |
| KR101008536B1 (en) | 2008-04-16 | 2011-01-14 | 포항공과대학교 산학협력단 | The method of separating and purifying cellular components using non-covalent bond between a cucurbituril derivative and a guest compound and an apparatus using the same |
| CN105642260B (en) * | 2014-12-02 | 2017-12-15 | 中国科学院大连化学物理研究所 | A kind of silicon dioxide microsphere stationary phase of dendroid carbon 18 and its preparation and application |
-
1998
- 1998-03-12 KR KR1019980009996A patent/KR100263872B1/en not_active IP Right Cessation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100454712B1 (en) * | 2001-08-03 | 2004-11-05 | 한국과학기술연구원 | Chiral stationary phases, chiral columns with the chiral stationary phases and process for producing the chiral stationary phases |
| KR20030077238A (en) * | 2002-03-25 | 2003-10-01 | 대한민국(부산대학교 총장) | Liquid chromatographic ligand exchange chiral stationary phases, chiral columns packed with the ligand exchange chiral stationary phases |
| KR20040021467A (en) * | 2002-09-04 | 2004-03-10 | 대한민국(부산대학교 총장) | Improved Crown Ether Chiral Statioary Phases and Chiral Columns for the Liquid Chromatographic Resolution of Chiral Drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| KR100263872B1 (en) | 2000-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4322310A (en) | Chiral supports for resolution of racemates | |
| Pirkle et al. | Useful and easily prepared chiral stationary phases for the direct chromatographic separation of the enantiomers of a variety of derivatized amines, amino acids, alcohols, and related compounds | |
| KR100263872B1 (en) | Liquid chromatographic chiral stationary phases and chiral columns for the resolution of racemic compounds containing primary amino group | |
| EP0469739B1 (en) | Stationary phase for enantiomeric resolution in liquid chromatography | |
| KR100387932B1 (en) | Crown Ether Chiral Statioary Phases and Chiral Columns for the Liquid Chromatographic Resolution of Chiral Drugs | |
| Iuliano et al. | Synthesis of a new family of four deoxycholic acid derived chiral stationary phases and their evaluation in the HPLC resolution of racemic compounds | |
| KR100364255B1 (en) | Crown Ether Chiral Stationary Phase and Chiral Column for the Liquid Chromatographic Resolution of Biologically Active Racemic Primary Amino Compounds | |
| Maier et al. | Efficient high-performance liquid chromatographic enantioseparation of five-membered aryl-substituted lactones and cyclic carbamates on a (R, R)-diaminodihydroethanoanthracene-derived chiral stationary phase | |
| KR100454712B1 (en) | Chiral stationary phases, chiral columns with the chiral stationary phases and process for producing the chiral stationary phases | |
| CN111793017A (en) | Preparation method of lactam compound | |
| KR100390765B1 (en) | Process for preparing (-)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, and (-)-chiral stationary phases for resolution of racemic compounds using the same | |
| KR101915010B1 (en) | Chiral stationary phases for the resolution of racemic compounds and preperation method of the same | |
| KR100547958B1 (en) | Chiral Crown Ether-Based LC Chiral Statioary Phases and Chiral Columns, and method of making them | |
| KR100520998B1 (en) | Liquid Chromatographic Crown Ether Chiral Statioary Phases with Double Tethering Groups and Chiral Columns Packed with Them | |
| KR100403977B1 (en) | Chiral stationary phase and chiral LC column for optical resolution of racemic compounds | |
| EP2239565B1 (en) | Optical-isomer separating agent for chromatography and process for producing the same | |
| KR100525288B1 (en) | Chiral stationary phases based on optically active n,n'-di(substituted benzoyl)-2,3-diamino-1,4-butanrdiol and the chiral columns packed with the chiral stationary phases | |
| KR100949758B1 (en) | Chiral stationary phase based on antibiotics cefaclor and chiral column | |
| JP3706160B2 (en) | Process for producing optically active diazabicycloheptene derivatives | |
| Oxelbark et al. | Effects from hydrogen bonding and rigidity on selectivity in tartaric acid‐based chiral selectors for enantioselective liquid chromatography | |
| KR20030077238A (en) | Liquid chromatographic ligand exchange chiral stationary phases, chiral columns packed with the ligand exchange chiral stationary phases | |
| KR101089808B1 (en) | Magnetic chiral stationary phase having the nano silica partcles and the separation method of the racemic compound in use of it | |
| CN104987305A (en) | Preparing method for 3-acetoxyl-methyl-2-(4-hydroxy-3-methoxy-benzyl)-4-(4-hydroxy-3-methoxy-phenyl)-2-nitro-3-thiophenyl-methyl butyrate | |
| JPS6314730A (en) | Optical resolution of alpha-substituted acetic acid ester | |
| KR20040021467A (en) | Improved Crown Ether Chiral Statioary Phases and Chiral Columns for the Liquid Chromatographic Resolution of Chiral Drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20030502 Year of fee payment: 5 |
|
| LAPS | Lapse due to unpaid annual fee |