CN104803909B - L‑哌啶甲酸的分离方法 - Google Patents
L‑哌啶甲酸的分离方法 Download PDFInfo
- Publication number
- CN104803909B CN104803909B CN201510268919.3A CN201510268919A CN104803909B CN 104803909 B CN104803909 B CN 104803909B CN 201510268919 A CN201510268919 A CN 201510268919A CN 104803909 B CN104803909 B CN 104803909B
- Authority
- CN
- China
- Prior art keywords
- piperidine carboxylic
- carboxylic acids
- resin
- catalytic
- separation method
- 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 - Fee Related
Links
- 238000000034 method Methods 0.000 title abstract description 13
- 239000011347 resin Substances 0.000 claims abstract description 42
- 229920005989 resin Polymers 0.000 claims abstract description 42
- 230000003197 catalytic effect Effects 0.000 claims abstract description 28
- 238000000926 separation method Methods 0.000 claims abstract description 21
- 239000007788 liquid Substances 0.000 claims abstract description 18
- 239000003480 eluent Substances 0.000 claims abstract description 12
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 9
- 239000012670 alkaline solution Substances 0.000 claims abstract description 8
- 238000011068 loading method Methods 0.000 claims abstract description 3
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 claims description 16
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- 238000001179 sorption measurement Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 abstract description 2
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 abstract description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 1
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
- 239000012530 fluid Substances 0.000 description 9
- 238000000855 fermentation Methods 0.000 description 8
- 230000004151 fermentation Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000012159 carrier gas Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 1
- YCAGGFXSFQFVQL-UHFFFAOYSA-N Endothion Chemical compound COC1=COC(CSP(=O)(OC)OC)=CC1=O YCAGGFXSFQFVQL-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 108010088495 lysine cyclodeaminase Proteins 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- -1 piperidine carboxylic acid compound Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108020001898 pyrroline-5-carboxylate reductase Proteins 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种L‑哌啶甲酸的分离方法，将含L‑哌啶甲酸的待分离液通过催化树脂，树脂吸附饱和后，以碱性溶液作为洗脱剂对树脂进行洗脱，收集洗脱液，将洗脱液结晶、干燥得到L‑哌啶甲酸。含L‑哌啶甲酸的待分离液通过催化树脂的流速为0.4~3 mL/min。所述催化树脂为D103‑MTBE或者WS‑3催化树脂。催化树脂填充量为每克湿树脂吸附0.1‑0.2 g L‑哌啶甲酸。所述碱性溶液为0.05‑0.1%（v/v）的氨水。该方法简单、方便，节约生产成本。
Description
技术领域
本发明涉及氨基酸的分离方法，具体涉及一种L-哌啶甲酸的分离方法。
背景技术
L-哌啶甲酸又名L-高脯氨酸，是L-赖氨酸的衍生物，可作为医药中间体或生物尼龙的生产前体。目前，国内外L-哌啶甲酸的生产多采用化学合成、光催化和生物催化方式。生物催化过程温和，且产物专一，极具应用潜力。日本Mercian 制药公司利用重组氨转移酶LAT 和同类的P5C 还原酶将L- 赖氨酸转化为L- 哌啶酸。尽管如此，生物法获得的L-哌啶甲酸的分离纯化，国内却尚无报道。
氨基酸类物质的树脂分离常用的是阳离子交换树脂。D103-MTBE催化树脂目前被用于合成甲基叔丁基醚（MTBE），甲基叔戊基醚（TAME），轻汽油醚化的催化剂，以及某些以强酸为催化剂和有机反应，以及作为催化剂载体等。目前还没有关于将D103-MTBE催化树脂用于类似L-哌啶甲酸发酵液这类生物制品分离的相关专利和报道。
发明内容
本发明提供了一种L-哌啶甲酸的分离方法，该方法简单方便、能耗低，可大幅度降低下游分离纯化成本。
本发明是通过以下技术方案实现的：
一种L-哌啶甲酸的分离方法，将含L-哌啶甲酸的待分离液通过催化树脂，树脂吸附饱和后，以碱性溶液作为洗脱剂对树脂进行洗脱，收集洗脱液，将洗脱液结晶、干燥得到L-哌啶甲酸。
含L-哌啶甲酸的待分离液通过催化树脂的流速为0.4~3 mL/min。
所述催化树脂为D103-MTBE催化树脂。
所述催化树脂为WS-3催化树脂。
催化树脂填充量为每克湿树脂吸附0.1-0.2 g L-哌啶甲酸。
所述碱性溶液为0.05-0.1%（v/v）的氨水。
含L-哌啶甲酸的待分离液通过催化树脂的流速优选为1mL/min。
所述碱性溶液优选体积浓度为0.1%的氨水。
本发明所述的结晶和干燥的方法可以为本领域公知的各种方法，包括但不限于溶剂蒸发、真空蒸发、低压真空干燥等。
发明人在实验中发现D103-MTBE或者WS-3催化树脂能够高效分离L-哌啶甲酸，并且待分离液中可以包含磷酸盐、L-赖氨酸等杂质。所述待分离液可以为微生物发酵生产L-哌啶甲酸所得的混合液，也可以为其他合成途径所得。本发明提供的分离方法，适用于将L-哌啶甲酸与某些理化特性与其相似的化合物例如磷酸盐、L-赖氨酸等分开，在树脂吸附洗脱之前可以先对待分离溶液做适当去杂处理，比如过滤。
由于本发明采用的是树脂吸附-洗脱来将L-哌啶甲酸与某些理化特性与其相似的化合物分开，因此本发明对所述含L-哌啶甲酸的待分离液中的L-哌啶甲酸浓度没有特别限定。一般地优选待分离液中含有的L-哌啶甲酸浓度为5-30 g/L， pH值为7.0-8.0。
有益效果：
本发明提供的L-哌啶甲酸的分离方法，简单方便、能耗低，分离得到的L-哌啶甲酸纯度高，收率高。
附图说明
图1为L-哌啶甲酸、L-赖氨酸含量分析的高效液相色谱图谱，图中，出峰时间2.720min、3.105min的物质为磷酸盐（磷酸氢二钾、磷酸二氢钾），出峰时间为5.273 min的物质为L-赖氨酸、出峰时间为19.104min的物质为L-哌啶甲酸。
具体实施方式
下面结合具体实施方式对本发明进行进一步的详细描述，给出的实施例仅为了阐述本发明，而不是限制本发明的范围。
L-哌啶甲酸溶液的制备
用发酵法制备：发酵底物为L-赖氨酸25 g/L，用50mM磷酸盐缓冲液（PBS缓冲液）调整发酵液pH为7.0-8.0。培养方法：将重组E.coliBL21(DE3)（Hanxiao Ying, Jing Wang,Zhen Wang, Jiao Feng, Kequan Chen, Yan Li, Ouyang Pingkai. Enhancedconversion of L-lysine to L-pipecolic acid using a recombinant Escherichiacoli containing lysine cyclodeaminase as whole-cell biocatalyst[J]. Journalof Molecular Catalysis B: Enzymatic, 2015, http://dx.doi.org/doi:10.1016/j.molcatb.2015.05.001）接入种子培养基（胰蛋白胨10g/L，酵母提取物5g/L, NaCl 10g/L，用1mM NaOH溶液调整培养基pH为 7.0-8.0），在37 ℃、200 rpm下培养18小时。20%的接种量接入1L发酵罐中的发酵培养基中，400 rpm、37 ℃下培养48小时。放罐时，L-哌啶甲酸的产量是10-20 g/L，然后将发酵液通过分子量50 KDa的超滤膜去掉菌体和大部分蛋白质，得到的溶液作为以下实施例中进行L-哌啶甲酸分离的待分离液。
L-哌啶甲酸和L-赖氨酸的浓度是通过美国Alltech 1500型高效液相色谱仪检测。检测条件为：Prevail C18色谱柱（250×4.6 mm，i.d. 5 μm）；柱温：30 ℃；流动相：0.4%（v/v）三氟乙酸水溶液；流速：0.5ml/min；检测器：蒸发光散射检测器（ELSD）；检测器温度：120℃；载气：氮气（纯度99.9%）；载气流速：4 L/min；进样体积：10 μL。
L-哌啶甲酸纯度为L-哌啶甲酸在结晶、干燥所得固形物中的质量百分比。
L-哌啶甲酸收率为结晶、干燥后所得L-哌啶甲酸与初始待分离L-哌啶甲酸的质量百分比。
实施例1
本实施例对上述发酵法制备得到的含L-哌啶甲酸的发酵液作进一步分离提纯，含L-哌啶甲酸的发酵液中L-哌啶甲酸10 g/L，L-赖氨酸2 g/L，磷酸盐 50 mM。
用35 g D103-MTBE催化树脂填充固定床，平衡后将含L-哌啶甲酸的待分离液上柱，流速0.4 mL/min，400 mL后吸附饱和，然后用0.05%（v/v）氨水进行洗脱，洗脱液体积为688 mL，经HPLC测定洗脱液中L-哌啶甲酸浓度为5.54 g/L。结晶、干燥后L-哌啶甲酸产品纯度97.8%，收率95.4%。
实施例2
本实施例对上述发酵法制备得到的含L-哌啶甲酸的发酵液作进一步分离提纯，含L-哌啶甲酸的发酵液中L-哌啶甲酸30 g/L，L-赖氨酸5 g/L，磷酸盐20 mM。
用200 gD103-MTBE催化树脂填充固定床，平衡后将含L-哌啶甲酸的待分离液上柱，流速1 mL/min，550 ml后吸附饱和，然后用0.1%（v/v）氨水进行洗脱，洗脱液体积为800ml，经HPLC测定洗脱液中L-哌啶甲酸浓度为13.66 g/L，结晶、干燥后L-哌啶甲酸产品纯度98.2%，收率99.1%。
实施例3
本实施例用于说明本发明提供的分离L-哌啶甲酸的方法。
本实施例对上述发酵法制备得到的含L-哌啶甲酸的发酵液作进一步分离提纯，含L-哌啶甲酸的发酵液中L-哌啶甲酸5 g/L，L-赖氨酸15 g/L，磷酸盐100 mM。
用15 gD103-MTBE催化树脂填充固定床，平衡后将含L-哌啶甲酸的待分离液上柱，流速3 ml/min，420 ml后吸附饱和，然后用0.08%（v/v）氨水进行洗脱，洗脱液体积为730ml，经HPLC测定洗脱液中L-哌啶甲酸浓度为1.94 g/L，结晶、干燥后L-哌啶甲酸产品纯度98.5%，收率98.6%。
实施例4
本实施例用于说明本发明提供的分离L-哌啶甲酸的方法与常规氨基酸分离方法的比较。
分别用25 gD103-MTBE催化树脂、WS-3催化树脂、WA-3氨基酸专用树脂、D001阳离子交换树脂、D113阳离子交换树脂、D002阳离子交换树脂，填充固定床，平衡后将800 mL浓度为14 g/L的L-哌啶甲酸溶液上柱，流速1 mL/min，吸附饱和后，然后用0.1%（v/v）氨水进行洗脱，结晶、干燥后测定L-哌啶甲酸的纯度和收率，结果见表1。
表1：
| D103-MTBE | WS-3 | WA-3 | D001 | D113 | D002 | |
| 纯度 | 98.6% | 96.4% | 86.5% | 67.9% | 72.7% | 63.8% |
| 收率 | 99.1% | 97.3% | 88.4% | 55.3% | 76.2% | 51.0% |
Claims (6)
1.一种L-哌啶甲酸的分离方法，其特征在于：所述分离方法适用于将L-哌啶甲酸与理化特性相似的磷酸盐、L-赖氨酸分开，将含L-哌啶甲酸的待分离液通过催化树脂，树脂吸附饱和后，以碱性溶液作为洗脱剂对树脂进行洗脱，收集洗脱液，将洗脱液结晶、干燥得到L-哌啶甲酸；所述催化树脂为D103-MTBE催化树脂或者WS-3催化树脂；所述碱性溶液为0.05-0.1%（v/v）的氨水。
2.根据权利要求1所述的L-哌啶甲酸的分离方法，其特征在于：含L-哌啶甲酸的待分离液通过催化树脂的流速为0.4~3 mL/min。
3.根据权利要求1所述的L-哌啶甲酸的分离方法，其特征在于：催化树脂填充量为每克湿树脂吸附0.1-0.2 g L-哌啶甲酸。
4.根据权利要求1所述的L-哌啶甲酸的分离方法，其特征在于：所述含L-哌啶甲酸的待分离液中含有的L-哌啶甲酸浓度为5-30 g/L。
5.根据权利要求1所述的L-哌啶甲酸的分离方法，其特征在于：所述碱性溶液为0.1%（v/v）的氨水。
6.根据权利要求2所述的L-哌啶甲酸的分离方法，其特征在于：含L-哌啶甲酸的待分离液通过催化树脂的流速为1mL/min。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510268919.3A CN104803909B (zh) | 2015-05-25 | 2015-05-25 | L‑哌啶甲酸的分离方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510268919.3A CN104803909B (zh) | 2015-05-25 | 2015-05-25 | L‑哌啶甲酸的分离方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104803909A CN104803909A (zh) | 2015-07-29 |
| CN104803909B true CN104803909B (zh) | 2017-08-29 |
Family
ID=53689150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510268919.3A Expired - Fee Related CN104803909B (zh) | 2015-05-25 | 2015-05-25 | L‑哌啶甲酸的分离方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104803909B (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974076A (zh) * | 2015-08-06 | 2015-10-14 | 南京工业大学 | 改进的l-哌啶甲酸的分离方法 |
| CN107286228A (zh) * | 2016-03-31 | 2017-10-24 | 南京诺云生物科技有限公司 | Arenimonas donghaensis DSM 18148蛋白的新用途 |
| CN106591387A (zh) * | 2016-12-21 | 2017-04-26 | 南京工业大学 | 一种基于微通道反应器一步酶催化合成哌啶甲酸的方法 |
| CN106831540B (zh) * | 2017-03-09 | 2019-06-11 | 爱斯特（成都）生物制药股份有限公司 | 一种（s）-3-哌啶甲酸的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3266635B2 (ja) * | 1991-12-11 | 2002-03-18 | 協和醗酵工業株式会社 | １−ピペコリン酸の製造法 |
| CN1415015B (zh) * | 1999-12-28 | 2011-12-14 | 美露香株式会社 | L-六氢吡啶羧酸的生物学制备方法 |
| JP2008007480A (ja) * | 2006-06-30 | 2008-01-17 | Mitsubishi Gas Chem Co Inc | Ｌ−ピペコリン酸の製造方法 |
| CN104402803A (zh) * | 2014-10-29 | 2015-03-11 | 宜兴市前成生物有限公司 | 一种l-高脯氨酸的制备方法 |
-
2015
- 2015-05-25 CN CN201510268919.3A patent/CN104803909B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN104803909A (zh) | 2015-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104803909B (zh) | L‑哌啶甲酸的分离方法 | |
| US20200199641A1 (en) | Method for enzymatic preparation of glutathione | |
| CN102336796B (zh) | 一种尼莫克汀的制备方法 | |
| CN111187798A (zh) | 一种高纯度甘油葡萄糖苷及其制备方法 | |
| CN100509760C (zh) | 四区模拟移动床分离纯化发酵液中的谷氨酰胺的方法 | |
| WO2017159555A1 (ja) | 還元型グルタチオンの結晶及びその製造方法 | |
| CN113402433A (zh) | 一种从鲜蒜中提取的含硫物质和大蒜素及其提取方法 | |
| CN105566136A (zh) | 一种从发酵液中分离提取4-羟基异亮氨酸的方法 | |
| CN111549015B (zh) | 一种利用色谱技术分离去除核酸酶液中桔霉素的工艺 | |
| CN106565425B (zh) | 一种从左旋多巴母液中回收邻苯二酚和左旋多巴的方法 | |
| Castillo et al. | Reversed-phase C18 high-performance liquid chromatography of gibberellins GA3 and GA1 | |
| CN105238841A (zh) | 头孢菌素c吸附废液中dcpc的回收与转化方法 | |
| US20140155658A1 (en) | Method for desorbing and regenerating butanol-adsorbing hydrophobic macroporous polymer adsorbent | |
| CN110396058A (zh) | 一种新型骨化二醇（25-羟基维生素d3）分离纯化方法 | |
| WO2012055253A1 (zh) | 一种辅酶q10层析硅胶的再生方法 | |
| CN112493484B (zh) | 一种富含梅素的青梅精及高纯度青梅梅素的制备方法 | |
| CN109705174B (zh) | 妥布霉素的提取方法 | |
| CN104974076A (zh) | 改进的l-哌啶甲酸的分离方法 | |
| CN112480127A (zh) | 一种生产丝裂霉素的新方法 | |
| CN112409426A (zh) | 一种硫酸西索米星的制备方法 | |
| CN112079886A (zh) | 一种经色谱分离提高木糖和***糖纯度的方法 | |
| US5180670A (en) | Method for purification of mitomycin C | |
| CN111778296B (zh) | 一种固定化酶催化生产槲皮素的方法 | |
| EP0009363B1 (en) | Method of separating cephalosporins | |
| CN114437963B (zh) | 橄榄链霉菌及其在生物合成香兰素中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170829 Termination date: 20190525 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |