KR100345994B1 - Process for enzymatically preparing 7-aminocephalosporanic acid - Google Patents
Process for enzymatically preparing 7-aminocephalosporanic acid Download PDFInfo
- Publication number
- KR100345994B1 KR100345994B1 KR1019940014231A KR19940014231A KR100345994B1 KR 100345994 B1 KR100345994 B1 KR 100345994B1 KR 1019940014231 A KR1019940014231 A KR 1019940014231A KR 19940014231 A KR19940014231 A KR 19940014231A KR 100345994 B1 KR100345994 B1 KR 100345994B1
- Authority
- KR
- South Korea
- Prior art keywords
- aca
- reaction
- hydrogen peroxide
- keto
- amino acid
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
- C12P35/06—Cephalosporin C; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y104/00—Oxidoreductases acting on the CH-NH2 group of donors (1.4)
- C12Y104/03—Oxidoreductases acting on the CH-NH2 group of donors (1.4) with oxygen as acceptor (1.4.3)
- C12Y104/03003—D-Amino-acid oxidase (1.4.3.3)
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Description
본 발명은 효소법에 의해 7-아미노세팔로스포란산(이하 7-ACA) 제조시 중간 물질인 글루타릴 7-아미노세팔로스포란산(이하 GL-7-ACA)의 수율 및 순도 향상을 위한 방법에 관한 것이다.The present invention improves the yield and purity of glutaryl 7-aminocephalosporranic acid (hereinafter referred to as GL-7-ACA), an intermediate in the preparation of 7-aminocephalosporonic acid (hereinafter referred to as 7-ACA) by the enzymatic method. It is about a method.
세파계 항생제의 전구물질인 7-ACA는 화학적 또는 효소적 합성에 의해 생산될 수 있는데 현제 전세계적으로 통용되고 있는 화학적 합성법은 원료로 사용되는 유기용매에 의한 환경오염문제와 제품중의 잔류 유기용매에 대한 규제의 강화로 점차 효소적 합성법으로 대체되고 있는 추세이다.7-ACA, a precursor of cephatic antibiotics, can be produced by chemical or enzymatic synthesis. Currently, the chemical synthesis method, which is widely used worldwide, is a problem of environmental pollution caused by organic solvents used as raw materials and residual organic solvents in products. Increasingly regulated, the trend is increasingly being replaced by enzymatic synthesis.
효소적 7-ACA 제조는 세팔로스포린C(이하 Cepha C)에 고정화된 효소 D-아미노산옥시다제를 작용시켜 산화적 탈아민화 반응을 거쳐 케토아디필7-아미노세팔로스포란산(이하 Keto-7-ACA)을 만든 다음 화학양론적 당량으로 과산화수소를 첨가하여 GL-7-ACA로 전환시킨 다음 GL-7-ACA 아실라제를 반응시켜 7-ACA를 제조한다. 그러므로 중간물질인 GL-7-ACA의 순도는 최종제품인 7-ACA의 품질에 상당한 영향을 미친다.Enzymatic 7-ACA preparation was carried out by the action of the enzyme D-amino acid oxidase immobilized on cephalosporin C (hereinafter referred to as Cepha C) to undergo an oxidative deamination reaction followed by ketoadifil 7-aminocephalosporonic acid (hereinafter referred to as Keto-). 7-ACA) is then converted to GL-7-ACA by adding a stoichiometric equivalent of hydrogen peroxide and then reacted with GL-7-ACA acylase to prepare 7-ACA. Therefore, the purity of the intermediate GL-7-ACA has a significant impact on the quality of the final product 7-ACA.
본 발명의 목적은 GL-7-ACA 아실라제 반응의 기질로 사용되는 GL-7-ACA의 수율 및 순도 향상을 위한 제조공정 개발에 있다.An object of the present invention is to develop a manufacturing process for improving the yield and purity of GL-7-ACA used as a substrate of the GL-7-ACA acylase reaction.
GL-7-ACA의 종래의 제조방법인 일본특허 공개 平5-211890에서는 농도 20-100 g/l 의 Cepha C 에 고정화 효소 D-아미노산옥시다제를 25℃, pH7.5에서 공기유량 0.5-1.0 vvm의 반응조건하에서 Keto-7-ACA를 만든 다음 화학양론적 당량의 과산화수소를 첨가시켜 20-25℃ 에서 10-15 분간 반응시켜 GL-7-ACA를 제조하며 반응 시간 단축을 위해서 과량의 과산화수소를 사용하여 반응 후 잔존 과산화수소는 피루브산 또는 이의 염 또는 알칼리성 설파이트와 같은 환원제를 사용하여 제거하였다. 이 제조방법은 산화적 카르복실 제거공정을 위해서 D-아미노산옥시다제를 반응물에서 분리하고 과량의 과산화수소를 제거하는 공정이 필요하여 공정이 단순화 되지 못하며 알칼리영역에서 불안정한 Keto-7-ACA가 분해되어 GL-7-ACA 외에 다른 불순물이 많이 발생될 단점을 가지고 있으며 미반응된 Keto-7-ACA는 최종제품에 불순물로 잔존하게 되는 단점을 가지고 있다.In Japanese Patent Laid-Open No. Hei 5-211890, which is a conventional method for preparing GL-7-ACA, an air flow rate of 0.5-1.0 is immobilized at 25 ° C. and pH 7.5 by immobilizing enzyme D-amino acid oxidase at Cepha C at a concentration of 20-100 g / l. Keto-7-ACA was prepared under the reaction conditions of vvm, and then the stoichiometric equivalent of hydrogen peroxide was added, followed by reaction at 20-25 ° C. for 10-15 minutes to produce GL-7-ACA, and excess hydrogen peroxide was added to reduce the reaction time. The remaining hydrogen peroxide after the reaction was removed using a reducing agent such as pyruvic acid or its salt or alkaline sulfite. This process requires the process of separating D-amino acid oxidase from the reactant and removing excess hydrogen peroxide for the oxidative carboxyl removal process, which does not simplify the process and decomposes the unstable Keto-7-ACA in the alkaline region, resulting in GL In addition to -7-ACA, there are disadvantages that other impurities are generated, and unreacted Keto-7-ACA has the disadvantage of remaining as impurities in the final product.
한편 PCT/US90/01696 의 제조공정에서는 50 psig 에서 고정화효소 D-아미노산옥시다제를 Cepha C 용액에 80분 동안 6 ml/min 속도로 재순환 시켜 GL-7-ACA 반응수율 90.6%를 보였다. 그러나 이 공정 에서는 반응 후 20분부터 미반응 Keto-7-ACA가 검출되어 반응종료시 까지 거의 같은 양으로 유지되어 GL-7-ACA 순도 및 수율이 낮았으며 효소반응 후 미반응 Keto-7-ACA의 GL-7-ACA로의 전환공정도 장시간 소요되어 자연분해에 의한 불순물의 발생 가능성이 많다.In the manufacturing process of PCT / US90 / 01696, the immobilized enzyme D-amino acid oxidase was recycled to Cepha C solution at 6 ml / min for 80 minutes at 50 psig, and the yield of GL-7-ACA reaction was 90.6%. In this process, however, unreacted Keto-7-ACA was detected from 20 minutes after the reaction and maintained at about the same amount until the end of the reaction, resulting in low purity and yield of GL-7-ACA. The conversion process to GL-7-ACA also takes a long time, and impurities are likely to be generated by natural decomposition.
따라서 본 발명자들은 기존의 제조법에서 발생되는 문제점을 해결하여 전체공정을 간편화시키고 GL-7-ACA의 반응수율 및 순도를 높이기 위한 방법을 연구하게 되었다.Therefore, the present inventors have solved the problems caused by the existing manufacturing method to simplify the whole process and to study a method for increasing the reaction yield and purity of GL-7-ACA.
본 제조공정은 고정화된 D-아미노산옥시다제를 온도 20-25℃, pH 7.1-8.0, 유량 1 vvm의 산소를 사용하여 압력 45-55 psig에서 10-30 g/l Cepha C용액을 효소반응시켜 GL-7-ACA를 제조하였다. 반응중 pH는 2M-KOH용액으로 초기pH를 유지시켰다. 초기pH가 높을수록 반응시간은 단축되나 중간생성물인 Keto-7-ACA가 알칼리 영역에서 불안정하므로 운전 pH는 7.2-7.6으로 하였다.In this process, the immobilized D-amino acid oxidase was enzymatically reacted with 10-30 g / l Cepha C solution at a pressure of 45-55 psig using oxygen at a temperature of 20-25 ° C., pH 7.1-8.0, and a flow rate of 1 vvm. GL-7-ACA was prepared. The pH during the reaction was maintained at the initial pH in 2M-KOH solution. The higher the initial pH, the shorter the reaction time, but the intermediate pH Keto-7-ACA is unstable in the alkaline region, so the operating pH was set to 7.2-7.6.
그런데 본 제조공정에서 발견된 문제점은 반응말기에 과산화수소가 부족하여 Keto-7-ACA의 GL-7-ACA로의 전환속도가 늦어지며 pH값이 초기보다 증가하는 경향을 보였다는 점이다. 그러므로 반응시간을 증가시켜도 미반응 Keto-7-ACA는 반응액 중에 남게되어 GL-7-ACA의 순도 및 수율이 떨어지는 요인이 된다.However, the problem found in this manufacturing process is the lack of hydrogen peroxide at the end of the reaction, the rate of conversion of Keto-7-ACA to GL-7-ACA is slow and the pH value tended to increase from the beginning. Therefore, even if the reaction time is increased, unreacted Keto-7-ACA remains in the reaction solution, which causes a drop in purity and yield of GL-7-ACA.
본 발명자들은 이러한 문제점을 해결하기 위하여 5-10%의 과산화수소용액을 반응액에 첨가함으로써 반응pH를 초기pH로 계속 유지시켰다. 일정시간 반응 후 반응액을 회수하여 분석한 결과 Keto-7-ACA는 검출되지 않았으며 GL-7-ACA의 순도 및 반응수율도 기존의 공정에서 보다 많이 개선되었다.In order to solve this problem, the inventors kept the reaction pH at the initial pH by adding 5-10% hydrogen peroxide solution to the reaction solution. After the reaction, the reaction solution was collected and analyzed. Keto-7-ACA was not detected, and the purity and reaction yield of GL-7-ACA were improved more than in the conventional process.
기존 기술과 비교하여 본 발명의 장점은 다음과 같다.Advantages of the present invention compared to the existing technology are as follows.
첫째 종래의 공정에서 과산화수소 첨가 및 과량의 과산화수소 환원공정을 생략함으로써 공정을 단순화시킬 수 있다. 즉 Keto-7-ACA의 GL-7-ACA로의 전환공정을 하나의 반응조 내에서 연속공정으로 실시함으로써 전체공정 시간을 단축시킬 수 있어 알칼리 영역에서 불안정한 Keto-7-ACA의 불순물로의 분해를 최소화시킬 수 있었다.First, the process can be simplified by omitting the addition of hydrogen peroxide and the reduction of the excess hydrogen peroxide in the conventional process. In other words, by converting Keto-7-ACA to GL-7-ACA in a continuous process in one reactor, the overall process time can be shortened, minimizing decomposition of unstable Keto-7-ACA to impurities in the alkaline region. I could make it.
둘째 과산화수소 부족에 의해서 Keto-7-ACA가 GL-7-ACA로 전환되는 속도가 둔화되는 시기를 pH의 변화만으로 간단히 인지할 수 있어 반응조 내Keto-7-ACA, GL-7-ACA, 과산화수소 등의 농도를 매번 분석해야하는 번거로움을 없앨 수 있다.Second, when the rate of conversion of Keto-7-ACA to GL-7-ACA is slowed due to the lack of hydrogen peroxide, it can be recognized simply by changing the pH, such as Keto-7-ACA, GL-7-ACA, hydrogen peroxide, etc. Eliminate the hassle of having to analyze the concentration every time.
셋째 효소역가가 감소되어 반응성이 떨어질때 과산화수소 첨가 시기와 속도도 반응중 pH만으로 쉽게 인지하여 탄력적으로 조절할 수 있다.Third, when the enzyme activity decreases and the reactivity decreases, the time and rate of hydrogen peroxide addition can be easily recognized by adjusting only the pH during the reaction.
넷째 본 제조공정에서는 미반응 Keto-7-ACA를 전부 GL-7-ACA로 전환시켜 수율 측면에서 볼때 종래의 공정인 일본특허 공개 平5-211890의 90-95% 보다 향상된 96-98%의 반응수율을 얻을 수 있다. 또한 GL-7-ACA의 순도 면에서도 종래의 공정에서는 Keto-7-ACA가 미량 존재하였으나 본 발명의 제조방법을 사용시 미량의 Keto-7-ACA도 존재하지 않기때문에 GL-7-ACA의 순도를 95%이상으로 개선시킬 수 있다.Fourth, in this manufacturing process, all unreacted Keto-7-ACA is converted to GL-7-ACA, resulting in a 96-98% reaction that is improved from 90-95% of the conventional Japanese Patent Publication No. Hei 5-211890 in terms of yield. Yield can be obtained. In addition, in terms of the purity of GL-7-ACA, a small amount of Keto-7-ACA was present in the conventional process, but since there is no trace amount of Keto-7-ACA when using the manufacturing method of the present invention, the purity of GL-7-ACA is increased. Can be improved to more than 95%.
본 발명에서 반응물의 분석은 HPLC를 사용하였으며 Cepha C, Keto-7-ACA, GL-7-ACA의 RT값은 각각 6.2-6.3, 9.3-9.4, 27.1-27,4 분 이였다.Analysis of the reactants in the present invention using HPLC and the RT values of Cepha C, Keto-7-ACA, GL-7-ACA were 6.2-6.3, 9.3-9.4, 27.1-27, 4 minutes, respectively.
다음의 실시예에서 본 발명을 좀 더 구체적으로 설명한다.The present invention is explained in more detail in the following examples.
실시예 1Example 1
정제된 Cepha C 10g 을 용해한 액 300ml를 2M-KOH로 pH를 7.1로 조절한 후고정화된 D-아미노산옥시다제 (600unit)를 온도 20℃, 압력 45-55 psig에서 산소 1.0vvm 유량의 반응조건 하에서 110분간 반응시킨 결과 70분부터 pH가 7.1이상으로 증가하기 시작했으며 Keto-7-ACA의 농도는 반응이 끝날 때까지 같은 수준을 유지하였다. GL-7-ACA의 반응순율은 91.9% 였으며 그 결과는 표 1과 같다.300 ml of a solution of 10 g of purified Cepha C was adjusted to pH 7.1 with 2M-KOH, and the immobilized D-amino acid oxidase (600 units) was reacted under a reaction condition of oxygen 1.0vvm flow rate at a temperature of 20 ° C. and a pressure of 45-55 psig. As a result of the reaction for 110 minutes, the pH started to increase above 7.1 at 70 minutes and the concentration of Keto-7-ACA was maintained at the same level until the end of the reaction. The reaction rate of GL-7-ACA was 91.9%, and the results are shown in Table 1.
실시예 2Example 2
정제된 Cepha C 20g을 용해한 액 600ml를 2-KOH로 pH7.4로 조절하여 고정화효소 D-아미노산옥시다제(1300unit)로 실시예1과 같은 반응조건에서 80분간 반응시킨 결과 표2와 같이 반응 62분 후부터 Keto-7-ACA의 양이 일정하게 유지되며 과산화수소 미첨가시 Keto-7-ACA의 GL-7-ACA로의 전환도 거의 없었다.600 ml of a solution of 20 g of purified Cepha C was adjusted to pH 7.4 with 2-KOH and reacted with immobilized enzyme D-amino acid oxidase (1300 units) for 80 minutes under the same reaction conditions as in Example 1. After minutes, the amount of Keto-7-ACA remained constant and there was little conversion of Keto-7-ACA to GL-7-ACA when hydrogen peroxide was not added.
실시예 3Example 3
실시예1과 같은 반응조건에서 Cepha C의 pH를 7.3으로 유지시켜 반응시킨 후 pH가 7.4로 증가하는 51분 후 5% 과산화수소용액을 유속 0.08 ml/min로 반응조 내에 첨가시킨 결과 표3과 같이 pH를 7.1로 유지할 때보다 반응이 빨리 진행되었으나 25분 후 pH가 다시 증가할때 반응을 종료하여 반응액을 분석한 결과 잔존 Keto-7-ACA는 미량 존재하였다. 그러므로 반응시간을 단축하기 위해서 과산화수소 첨가 유속을 좀 더 빨리할 필요가 있다.After maintaining the pH of Cepha C at 7.3 under the same reaction conditions as in Example 1, 5% hydrogen peroxide solution was added to the reactor at a flow rate of 0.08 ml / min after 51 minutes of increasing the pH to 7.4. The reaction proceeded faster than when the pH was maintained at 7.1, but when the pH was increased again after 25 minutes, the reaction was terminated and the reaction solution was analyzed. As a result, a small amount of remaining Keto-7-ACA was present. Therefore, in order to shorten the reaction time, it is necessary to increase the flow rate of hydrogen peroxide.
실시예 4Example 4
실시예2와 같은 반응조건에서 pH를 2M-KOH로 7.2를 유지시키며 반응시킨 후 pH가 7.3으로 증가하는 55분 후 5% 과산화수소를 0.24 ml/min유속으로 25분간 첨가한 결과 표3과 같이 잔존 Keto-7-ACA는 검출되지 않았으며 GL-7-ACA 순도는 95.5%까지 증가하였다.Under the same reaction conditions as in Example 2, the pH was maintained at 2M-KOH at 7.2, followed by 55 minutes of increasing the pH to 7.3, followed by the addition of 5% hydrogen peroxide at a flow rate of 0.24 ml / min for 25 minutes. Keto-7-ACA was not detected and the GL-7-ACA purity increased to 95.5%.
실시예 5Example 5
실시예2와 같은 반응 조건에서 pH를 7.4로 유지시키며 pH가 7.5로 증가할 때 10% 과산화수소용액을 0.2 ml/min의 유속으로 15분 동안 첨가시킨 결과 표5와 같이 Keto-7-ACA는 전부 GL-7-ACA로 전환 되었으며 GL-7-ACA 반응수율은 96.7% 였다.Under the same reaction conditions as Example 2, the pH was maintained at 7.4 and when the pH was increased to 7.5, 10% hydrogen peroxide solution was added at a flow rate of 0.2 ml / min for 15 minutes. It was converted to GL-7-ACA and the yield of GL-7-ACA reaction was 96.7%.
실시예 6Example 6
실시예5와 같은 방법으로 초기 Cepha C용액의 pH별 최종반응액의 순도와 반응완료시간을 비교한 결과 표6과 같이 반응은 pH 7.1에서 pH 8.0 까지 가능하며 pH가 높을수록 반응 완료시간은 단축되나 pH 7.6이상에서는 Keto-7-ACA가 불안정하여 불순물로 전환되면서 순도는 낮아졌다. 그러므로 반응속도와 GL-7-ACA 순도를 고려할 때 반응 pH는 7.6이하가 적당하다.Comparing the purity and reaction completion time of the final reaction solution by pH of the initial Cepha C solution in the same manner as in Example 5, the reaction is possible from pH 7.1 to pH 8.0 as shown in Table 6, the higher the pH, the shorter the reaction completion time However, above pH 7.6, the purity was lowered as Keto-7-ACA was unstable and converted to impurities. Therefore, considering the reaction rate and GL-7-ACA purity, the reaction pH is less than 7.6.
제1도 : 실시예 4에서 과산화수소 첨가 전 반응액의 고속액체크로마토그라피(HPLC) 에 의한 크로마토그램1: Chromatogram by High Performance Liquid Chromatography (HPLC) of the reaction solution before hydrogen peroxide addition in Example 4
제2도 : 실시예 4에서 5%과산화수소 첨가 15분 후 HPLC 크로마토그램Figure 2: HPLC chromatogram 15 min after addition of 5% hydrogen peroxide in Example 4
제3도 : 실시예 4에서 5%과산화수소 첨가 25분 후 HPLC 크로마토그램Figure 3: HPLC chromatogram 25 min after addition of 5% hydrogen peroxide in Example 4
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019940014231A KR100345994B1 (en) | 1994-06-22 | 1994-06-22 | Process for enzymatically preparing 7-aminocephalosporanic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019940014231A KR100345994B1 (en) | 1994-06-22 | 1994-06-22 | Process for enzymatically preparing 7-aminocephalosporanic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
KR960001132A KR960001132A (en) | 1996-01-25 |
KR100345994B1 true KR100345994B1 (en) | 2002-12-16 |
Family
ID=37488665
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019940014231A KR100345994B1 (en) | 1994-06-22 | 1994-06-22 | Process for enzymatically preparing 7-aminocephalosporanic acid |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR100345994B1 (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4774179A (en) * | 1984-07-10 | 1988-09-27 | Asahi Kasei Kogyo Kabushiki Kaisha | Process for preparing a 7-aminocephalosporanic acid compound |
EP0322032A2 (en) * | 1987-12-21 | 1989-06-28 | Merck & Co. Inc. | One-step enzymatic conversion of cephalosporin C and derivatives to 7-aminocephalosporanic acid and derivatives |
WO1990012110A1 (en) * | 1989-04-04 | 1990-10-18 | Biopure Corporation | Enzymatic production of 7-amino cephalosporanic acid |
EP0496993A1 (en) * | 1990-12-21 | 1992-08-05 | ANTIBIOTICOS, S.p.A. | Enzymatic process for preparing 7-aminocephalosporanic acid and derivatives |
EP0525861A1 (en) * | 1991-07-24 | 1993-02-03 | Ministero Dell' Universita' E Della Ricerca Scientifica E Tecnologica | Process for the enzymatic preparation of 7-amino-cephalosporanic acids |
-
1994
- 1994-06-22 KR KR1019940014231A patent/KR100345994B1/en not_active IP Right Cessation
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4774179A (en) * | 1984-07-10 | 1988-09-27 | Asahi Kasei Kogyo Kabushiki Kaisha | Process for preparing a 7-aminocephalosporanic acid compound |
EP0322032A2 (en) * | 1987-12-21 | 1989-06-28 | Merck & Co. Inc. | One-step enzymatic conversion of cephalosporin C and derivatives to 7-aminocephalosporanic acid and derivatives |
WO1990012110A1 (en) * | 1989-04-04 | 1990-10-18 | Biopure Corporation | Enzymatic production of 7-amino cephalosporanic acid |
EP0496993A1 (en) * | 1990-12-21 | 1992-08-05 | ANTIBIOTICOS, S.p.A. | Enzymatic process for preparing 7-aminocephalosporanic acid and derivatives |
EP0525861A1 (en) * | 1991-07-24 | 1993-02-03 | Ministero Dell' Universita' E Della Ricerca Scientifica E Tecnologica | Process for the enzymatic preparation of 7-amino-cephalosporanic acids |
Also Published As
Publication number | Publication date |
---|---|
KR960001132A (en) | 1996-01-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4246347A (en) | Process for the production of fructose | |
Conlon et al. | Two‐step immobilized enzyme conversion of cephalosporin C to 7‐aminocephalosporanic acid | |
EP0801683B1 (en) | Racemate separation of primary and secondary heteroatom-substituted amine by enzyme-catalysed acylation | |
US5525483A (en) | Process for preparation of β-lactams utilizing a combined concentration of acylating agent plus β-lactam derivative of at least 400 mm | |
EP0322032A2 (en) | One-step enzymatic conversion of cephalosporin C and derivatives to 7-aminocephalosporanic acid and derivatives | |
EP0042221B1 (en) | Production of 2-keto-d-gluconic acid and hydrogen peroxide | |
KR100345994B1 (en) | Process for enzymatically preparing 7-aminocephalosporanic acid | |
Pilone et al. | A process for bioconversion of cephalosporin C by Rhodotorula gracilis D-amino acid oxidase | |
US5166061A (en) | Process for the production of 4-halo-3-hydroxybutyronitrile with Corynebacterium or Microbacterium | |
US4423149A (en) | Process for the production of D-glucosone | |
EP0283218B1 (en) | One-step enzymatic conversion of cephalosporin c and derivatives to 7-aminocephalosporanic acid and derivatives | |
CN1531598A (en) | Enzymatic process for preparing cephalosporanic acid derivatives | |
CN1316011A (en) | Continuous process for preparing optically pure (S)-3,4-dihydroxybutyric acid derivatives | |
EP1197563B1 (en) | Method for Producing Amino Acids | |
US6174707B1 (en) | Process for producing L-allysine acetals | |
CN1087350C (en) | Process for enzymatic synthesis of beta-lactam antibiotics in presence of enzyme inhibitor | |
US6319684B1 (en) | Process for the fermentative production of cephalosporin | |
HUT62940A (en) | Process for the enzymatic hydrolysis of carboxylic acid derivatives | |
Theil et al. | Enzymes in organic synthesis. 2. Synthesis of enantiomerically pure prostaglandin intermediates by Enzymatic Hydrolysis of (1SR, 5RS, 6RS, 7RS)‐7‐acetoxy‐6‐acetoxymethyl‐2‐oxabicyclo [3.3. 0] octan‐3‐one | |
US5707837A (en) | Method of producing (R)-tertiary leucine | |
KR100512774B1 (en) | Preparation of cephalosporin C broth for manufacturing 7-aminocephalosporanic acid | |
KR970010133B1 (en) | PROCESS FOR PREPARING D-Ñß-AMINO ACIDS | |
JP3647065B2 (en) | Method for producing optically active alanine | |
US5348882A (en) | Method of producing enantiomerically pure, open-chain N-alkyl-L or D-amino acids using comamonas testosteroni | |
JP2001120295A (en) | Method for producing d-(3'-pyridyl)-alanine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20080626 Year of fee payment: 7 |
|
LAPS | Lapse due to unpaid annual fee |