CN111549539A - 一种手性固膜及其在手性拆分中的应用 - Google Patents
一种手性固膜及其在手性拆分中的应用 Download PDFInfo
- Publication number
- CN111549539A CN111549539A CN202010534558.3A CN202010534558A CN111549539A CN 111549539 A CN111549539 A CN 111549539A CN 202010534558 A CN202010534558 A CN 202010534558A CN 111549539 A CN111549539 A CN 111549539A
- Authority
- CN
- China
- Prior art keywords
- chiral
- dinaphthyl
- crown
- diphenyl
- film
- 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
- 239000007787 solid Substances 0.000 title claims abstract description 56
- 239000012528 membrane Substances 0.000 title claims description 53
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 claims abstract description 20
- LJCWONGJFPCTTL-UHFFFAOYSA-N 4-hydroxyphenylglycine Chemical compound OC(=O)C(N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-UHFFFAOYSA-N 0.000 claims abstract description 17
- 150000001413 amino acids Chemical class 0.000 claims abstract description 6
- 230000003287 optical effect Effects 0.000 claims abstract description 4
- 229920000642 polymer Polymers 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- 238000000502 dialysis Methods 0.000 claims description 23
- 239000000243 solution Substances 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 13
- 238000005266 casting Methods 0.000 claims description 11
- 238000000926 separation method Methods 0.000 claims description 11
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- 238000007790 scraping Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 9
- 239000004745 nonwoven fabric Substances 0.000 claims description 9
- 239000004695 Polyether sulfone Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 229920006393 polyether sulfone Polymers 0.000 claims description 6
- 238000002791 soaking Methods 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 5
- 239000011159 matrix material Substances 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 238000009210 therapy by ultrasound Methods 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 3
- 241000238424 Crustacea Species 0.000 claims description 2
- 239000004952 Polyamide Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000005557 chiral recognition Methods 0.000 claims description 2
- 229920002492 poly(sulfone) Polymers 0.000 claims description 2
- 229920002647 polyamide Polymers 0.000 claims description 2
- 229920000728 polyester Polymers 0.000 claims description 2
- 238000004134 energy conservation Methods 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 210000004379 membrane Anatomy 0.000 description 47
- 239000003814 drug Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 7
- 230000004907 flux Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960003433 thalidomide Drugs 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000036244 malformation Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 229920005597 polymer membrane Polymers 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
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 1
- 229960001931 ampicillin sodium Drugs 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
- HVFLCNVBZFFHBT-ZKDACBOMSA-N cefepime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1C[N+]1(C)CCCC1 HVFLCNVBZFFHBT-ZKDACBOMSA-N 0.000 description 1
- 229960002100 cefepime Drugs 0.000 description 1
- -1 cefotrozine Chemical compound 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920000344 molecularly imprinted polymer Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000005331 phenylglycines Chemical class 0.000 description 1
- IVBHGBMCVLDMKU-GXNBUGAJSA-N piperacillin Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 IVBHGBMCVLDMKU-GXNBUGAJSA-N 0.000 description 1
- 229960002292 piperacillin Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Images
Classifications
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06N—WALL, FLOOR, OR LIKE COVERING MATERIALS, e.g. LINOLEUM, OILCLOTH, ARTIFICIAL LEATHER, ROOFING FELT, CONSISTING OF A FIBROUS WEB COATED WITH A LAYER OF MACROMOLECULAR MATERIAL; FLEXIBLE SHEET MATERIAL NOT OTHERWISE PROVIDED FOR
- D06N3/00—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof
- D06N3/12—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof with macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. gelatine proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/34—Preparation of optical isomers by separation of optical isomers
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06N—WALL, FLOOR, OR LIKE COVERING MATERIALS, e.g. LINOLEUM, OILCLOTH, ARTIFICIAL LEATHER, ROOFING FELT, CONSISTING OF A FIBROUS WEB COATED WITH A LAYER OF MACROMOLECULAR MATERIAL; FLEXIBLE SHEET MATERIAL NOT OTHERWISE PROVIDED FOR
- D06N3/00—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof
- D06N3/0002—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof characterised by the substrate
- D06N3/0011—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof characterised by the substrate using non-woven fabrics
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06N—WALL, FLOOR, OR LIKE COVERING MATERIALS, e.g. LINOLEUM, OILCLOTH, ARTIFICIAL LEATHER, ROOFING FELT, CONSISTING OF A FIBROUS WEB COATED WITH A LAYER OF MACROMOLECULAR MATERIAL; FLEXIBLE SHEET MATERIAL NOT OTHERWISE PROVIDED FOR
- D06N3/00—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof
- D06N3/0056—Artificial leather, oilcloth or other material obtained by covering fibrous webs with macromolecular material, e.g. resins, rubber or derivatives thereof characterised by the compounding ingredients of the macro-molecular coating
- D06N3/0061—Organic fillers or organic fibrous fillers, e.g. ground leather waste, wood bark, cork powder, vegetable flour; Other organic compounding ingredients; Post-treatment with organic compounds
-
- 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)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Textile Engineering (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
一种手性固膜及其在手性拆分中的应用,手性固膜为R‑(3,3'‑二苯基‑1,1'‑二萘基)‑20‑冠‑6手性固膜,是由R‑(3,3'‑二苯基‑1,1'‑二萘基)‑20‑冠‑6与高分子聚合物混合后溶解于有机溶剂中制得;采用所述制得的R‑(3,3'‑二苯基‑1,1'‑二萘基)‑20‑冠‑6手性固膜应用于在所述苯甘氨酸、对羟基苯甘氨酸两种氨基酸外消旋体光学拆分中。本发明的优点为:获得的对映体纯度相对较高、成本低、节能、环保、易于连续操作和大规模工业生产。
Description
技术领域
本发明属于高分子膜手性分离技术,具体地涉及一种R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性高分子固膜在苯甘氨酸、对羟基苯甘氨酸外消旋体拆分中的应用。
背景技术
手性是自然界本质属性之一,例如形成生物体的核酸、蛋白质、酶、多糖都是自然界先天存在的手性物质。手性问题涉及农业、食品、药物、材料、等众多领域,与我们日常生活密切相关。在接近于2000种常用药物中,约有500种都是以外消旋体形式存在。外消旋体药物,通常是一种立体的异构体具有药理活性,而它的镜像分子往往没有药理活性,甚至还可能具有毒副作用。如20世纪的“畸形海豹婴儿”事件,是由手性药物“沙利度胺”中的S构型所导致。沙利度胺中R构型可以防止怀孕时期出现的呕吐症状,但当时的人们却不知道S构型的沙利度胺会使孕妇对胎儿的供血有阻碍作用,导致婴儿畸形,由于这些惨痛的教训,使人们更加重视单手性药物获取。
目前,制备单手性异构体主要有天然来源、不对称合成、外消旋体拆分三种方法。但目前天然的手性异构体种类有限,且在生成过程常常会出现消旋化;而不对称合成获得的单一手性药物有些还存在技术的问题和经济性问题,如成本较高、对映体过剩值(e.e.%)较低,总体使用的范围较窄;虽然手性拆分技术有机械拆分法、化学拆分法、分子印迹聚合物拆分法、色谱拆分法和膜拆分法等,但综合规模生产、环保、节能、低成本等优势当属手性高分子膜拆分法。
苯甘氨酸与对羟基苯甘氨酸都是重要的药物合成中间体,常用于生产头孢克罗、头孢立新、哌拉西林、氨苄西林钠、头孢曲嗪、阿莫西林、头孢羟氨苄、苯咪唑青霉素等β-内酰氨类抗生素。由于它们都具有旋光性,并且右旋和左旋两种异构体又具有不同的作用,在医药上常用其一种对映体于药物生产。而我国是抗生素类药物生产和需求大国,半合成头孢菌素和半合成青霉素药物已成为制药行业的发展重点、热点。因此,从苯甘氨酸与对羟基苯甘氨酸外消旋体中分离获得单一异构体就显得尤为重要。迄今,还尚未见将R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6用作手性固膜的文献报道。
发明内容
本发明的目的在于克服现有技术之不足,提供一种R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6聚醚砜固膜的制备及其在苯甘氨酸、对羟基苯甘氨酸外消旋体拆分中的应用。
本发明的上述目的是通过以下的技术方案予以实现的:
一种手性固膜及其在手性拆分中的应用,手性固膜为R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜,是由R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6与高分子聚合物混合后,再溶解于有机溶剂中制得;其中:R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜由下述步骤制备而得:
a、干燥的商品聚醚砜作为基体,溶解于干燥的N,N-二甲基甲酰胺中;
b、搅拌24h溶解、超声1h出去气泡,除去聚集颗粒分子、24h静置脱泡;
c、取上述溶液加入含量为12%的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6再搅拌24h,静置24h,形成均匀的铸膜液;
d、室温条件下将铸膜液倾倒在光滑、干净的无纺布上,用刮膜刀刮成0.05mm~0.2mm厚度的膜;
e、挥发10min后,放入0℃去离子水中浸泡5h,最后放入去离子水中保持备用;
采用所述R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜应用于在所述苯甘氨酸、对羟基苯甘氨酸两种氨基酸外消旋体光学拆分中。
本发明将R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜分别作为拆分苯甘氨酸、对羟基苯甘氨酸外消旋体的应用。
本发明所述固膜材料为聚砜类或聚酯类或聚酰胺类或纤维素衍生物类或甲壳类的多功能性质高分子物质和R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6。
本发明所述应用是,用具有手性识别能力的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6作为膜的手性选择识别剂通过溶液制备分离固膜,用于苯甘氨酸、对羟基苯甘氨酸外消旋体的拆分。
本发明所述应用是R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜拆分苯甘氨酸、对羟基苯甘氨酸外消旋体包括下述步骤:
a、干燥的商品聚醚砜作为基体,溶解于干燥的N,N-二甲基甲酰胺中;
b、搅拌24h溶解、超声1h,除去聚集颗粒分子、24h静置脱泡;
c、取上述溶液加入含量为12%的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6再搅拌24h,静置24h,形成均匀的铸膜液;
d、室温条件下将铸膜液倾倒在光滑、干净的无纺布上,用刮膜刀刮成0.05~0.2mm厚度的膜;
e、挥发10min,放入0℃去离子水中浸泡5h,最后放入去离子水中保持备用;
f、将上述制备好的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜装入常规渗析装置中,采用浓度差驱动的膜过程,在0.2~0.8mg/mL浓度差作为驱动力,分别拆分浓度为0.2~0.8mg/mL的苯甘氨酸、对羟基苯甘氨酸外消旋体水溶液,水溶液的pH值是pH值=2的高氯酸,在室温25℃条件,在室温25℃条件,渗析4~15d。
与现有技术相比,本发明具有以下优点:
1、本发明R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜拆分苯甘氨酸外消旋体所得对映异构体纯度(e.e.%)达到76%以上,能实现对映体较高纯度的分离;其拆分对羟基苯甘氨酸外消旋体所得对映异构体纯度(e.e.%)达到24%以上,能实现对映体的基本分离;
2、膜拆分过程在常温下进行,不会发生相变化,而且驱动力是浓度差,因此能耗低;
3、膜拆分过程不添加新的化学试剂,因此环保,成本低;
4、膜分离易于连续操作,易进行大规模工业生产。
附图说明
图1为R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6的分子结构式;
图2为R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜的渗析装置图;
其中,1.原料液池;2.膜;3.接收液池;
图3为实施例1R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜的扫描电镜图;
图4为实施例2采用本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜不同厚度的色谱图;
图5为实施例3采用本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜不同渗析时间的色谱图;
图6为实施例4采用本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜渗析不同浓度的色谱图;
图7(a)中为实施例5采用本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜对苯甘氨酸进行选择性渗析的色谱图;图7(b)为实施例5采用本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜对于对羟基苯甘氨酸进行选择性渗析的色谱图。
具体实施方式
结合附图和实施列,对本发明的实质性内容作进一步详细描述,但本发明的内容并不局限于此。
实施例1
本发明的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜,其步骤制备如下:
a、干燥的商品聚醚砜作为基体,溶解于干燥的N,N-二甲基甲酰胺中;
b、搅拌24h溶解、超声1h,除去聚集颗粒分子、24h静置脱泡;
c、取上述溶液加入含量为12%的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6再搅拌24h,静置24h,形成均匀的铸膜液;
d、室温条件下将铸膜液倾倒在光滑、干净的无纺布上,用刮膜刀刮成0.1mm厚度的膜;
e、挥发10min,放入0℃去离子水中浸泡5h,最后放入去离子水中保持备用;
将上述制备R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜依次浸泡在无水的异丙醇、无水正己烷中浸泡24h,然后放入液氮中冷冻5-7min,用镊子折断,得到膜的截面。再真空环境下将膜面、膜截面进行喷金处理后,通过扫描电镜(SEM)得到表面和截面形态。具体见图3。
由图3可知:R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜已经均匀搅拌在基膜溶液中。
实施例2
因为在膜技术领域膜通量和选择渗析成反比,考虑到膜通量和渗析的时间周期的大小,在相同条件下,采用实施例1制备(1)0.05mm、(2)0.1mm、(3)0.2mm的3组不同厚度的本发明手性固膜,将其固定在图2的常规渗析装置上,在手性固定膜的膜一侧(膜面)渗析pH=2.0的高氯酸作为溶剂的氨基酸溶液,膜另一侧(膜背面)加入高纯水(渗析液),进行渗析,取渗析液,进行烘干测样。测定结果见表1及图4。
对映体选择性渗透百分率(enantiomeric excess,e.e.%)、透过液中D,L-对映面积(AD、AL)、百分率(e.e.%)的计算公式如下:
表1不同厚度的本发明手性固膜拆分苯甘氨酸的检测结果
综合表1和图4中可知:手性固膜的厚度为0.1mm,其兼顾渗析选择能力和膜通量大小。
实施例3
在实施例2确定条件下,在相同条件下,将本发明的手性固膜(实施例1所得),分别渗析:5d、9d、12d及15d,进行其渗析不同时间的确定。测定结果见表2及图5所示。
表2不同渗析时间的本发明手性固膜拆分苯甘氨酸的检测结果
从表2和图5中可知:渗析时间为15d时,手性固膜选择渗析最好
实施例4
考虑到实施例3的确定条件下周期长,在本实施例中选择可以准确检测到拆分物质的时间9d,在相同条件下,将本发明的手性固膜(实施例1所得),分别将其渗析不同浓度的苯甘氨酸:0.2mg/mL、0.4mg/mL、0.6mg/mL、0.8mg/mL,测定结果见表3及图6所示。
表3渗析不同浓度的本发明手性固膜拆分苯甘氨酸的检测结果
综合表3和图6中可知:渗析浓度为0.2mg/mL时,手性固膜选择渗析性最佳,但其膜通量较小。渗析浓度为0.8mg/mL时,手性固膜膜通量最佳,但其膜选择渗析能力差。
实施例5
在不虑膜通量的前提,实施例3的确定条件下,在本实施例中选择渗析选择性高的时间15d,再结合实施例4的确定条件下,在本实施例中选择膜选择渗析性最佳的浓度0.2mg/mL,在相同条件下,将本发明的手性固膜(实施例1所得),分别将其渗析不同氨基酸,测定结果见表4及图图7(a)、7(b)所示。
表4本发明手性固膜拆分不同氨基酸的检测结果
从表4和图7(a)、7(b)中可知:在不考虑膜通量的前提下,通过渗析,透过液中苯甘氨酸、对羟基苯甘氨酸对映体的纯度分别可达可达77%、24%以上。
Claims (4)
1.一种手性固膜及其在手性拆分中的应用,其特征在于,手性固膜为R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜,是由R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6与高分子聚合物混合后溶解于有机溶剂中制得;其中:R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜由下述步骤制备而得:
a、干燥的商品聚醚砜作为基体,溶解于干燥的N,N-二甲基甲酰胺中;
b、搅拌24h溶解、超声1h,除去聚集颗粒分子、24h静置脱泡;
c、取上述溶液加入含量为12%的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6再搅拌24h,静置24h,形成均匀的铸膜液;
d、室温条件下将铸膜液倾倒在光滑、干净的无纺布上,用刮膜刀刮成0.05~0.2mm厚度的膜;
e、挥发10min后,放入0℃去离子水中浸泡5h,最后放入去离子水中保持备用;
采用所述R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜应用于在所述苯甘氨酸、对羟基苯甘氨酸两种氨基酸外消旋体光学拆分中。
2.如权利要求1所述的一种手性固膜及其在手性拆分中的应用,其特征在于:所述固膜材料为聚砜类或聚酯类或聚酰胺类或纤维素衍生物类或甲壳类的多功能性质高分子物质和R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6。
3.如权利要求1所述的一种手性固膜及其在手性拆分中的应用,其特征在于:所述应用是,用具有手性识别能力的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6作为膜的手性选择识别剂通过溶液制备分离固膜,用于苯甘氨酸、对羟基苯甘氨酸外消旋体的拆分。
4.如权利要求1或3所述的一种手性固膜及其在手性拆分中的应用,其特征在于,所述应用是R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜拆分苯甘氨酸、对羟基苯甘氨酸外消旋体包括下述步骤:
a、干燥的商品聚醚砜作为基体,溶解于干燥的N,N-二甲基甲酰胺中;
b、搅拌24h溶解、超声1h,除去聚集颗粒分子、24h静置脱泡;
c、取上述溶液加入含量为12%的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6再搅拌24h,静置24h,形成均匀的铸膜液;
d、室温条件下将铸膜液倾倒在光滑、干净的无纺布上,用刮膜刀刮成0.05~0.2mm厚度的膜;
e、挥发10min,放入0℃去离子水中浸泡5h,最后放入去离子水中保持备用;
f、将上述制备好的R-(3,3'-二苯基-1,1'-二萘基)-20-冠-6手性固膜装入常规渗析装置中,采用浓度差驱动的膜过程,在0.2~0.8mg/mL浓度差作为驱动力,分别拆分浓度为0.2~0.8mg/mL的苯甘氨酸、对羟基苯甘氨酸外消旋体水溶液,水溶液的pH值是pH值=2的高氯酸,在室温25℃条件,在室温25℃条件,渗析4~15d。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010534558.3A CN111549539A (zh) | 2020-06-12 | 2020-06-12 | 一种手性固膜及其在手性拆分中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010534558.3A CN111549539A (zh) | 2020-06-12 | 2020-06-12 | 一种手性固膜及其在手性拆分中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111549539A true CN111549539A (zh) | 2020-08-18 |
Family
ID=71997505
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010534558.3A Pending CN111549539A (zh) | 2020-06-12 | 2020-06-12 | 一种手性固膜及其在手性拆分中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111549539A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116478396A (zh) * | 2022-01-14 | 2023-07-25 | 天津工业大学 | 一种用于盐湖提锂的二苯并-14-冠-4聚酰胺的制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107596927A (zh) * | 2017-11-10 | 2018-01-19 | 北京化工大学 | 一种手性纳米纤维复合膜及其制备方法 |
-
2020
- 2020-06-12 CN CN202010534558.3A patent/CN111549539A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107596927A (zh) * | 2017-11-10 | 2018-01-19 | 北京化工大学 | 一种手性纳米纤维复合膜及其制备方法 |
Non-Patent Citations (3)
Title |
---|
ALEIX CONESA: "Membrane thickness and preparation temperature as key parameters for controlling the macrovoid structure of chiral activated membranes (CAM)", 《JOURNAL OF MEMBRANE SCIENCE》 * |
宋航: "《制药分离工程》", 31 August 2011, 华东理工大学出版社 * |
路振宇: "冠醚手性固定相的合成及其性能评价", 《有机化学》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116478396A (zh) * | 2022-01-14 | 2023-07-25 | 天津工业大学 | 一种用于盐湖提锂的二苯并-14-冠-4聚酰胺的制备方法 |
CN116478396B (zh) * | 2022-01-14 | 2024-05-07 | 天津工业大学 | 一种用于盐湖提锂的二苯并-14-冠-4聚酰胺的制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ke et al. | Novel chiral composite membrane prepared via the interfacial polymerization of diethylamino-beta-cyclodextrin for the enantioseparation of chiral drugs | |
Liu et al. | Solid membranes for chiral separation: A review | |
Song et al. | Recent advances, challenges and perspectives in enantioselective release | |
Yilmaz et al. | Calixarene-based receptors for molecular recognition | |
CN104892710B (zh) | 一种纯化还原型β‑烟酰胺腺嘌呤二核苷酸的方法 | |
CN101486637A (zh) | 从发酵液中提取丁二酸的方法 | |
CN111549539A (zh) | 一种手性固膜及其在手性拆分中的应用 | |
Ingole et al. | Methods for separation of organic and pharmaceutical compounds by different polymer materials | |
CN104231303B (zh) | 一种分子印迹复合膜的制备方法及其应用 | |
Strathmann | Membranes and membrane processes in biotechnology | |
Xiong et al. | Chiral separation of (R, S)-2-phenyl-1-propanol through glutaraldehyde-crosslinked chitosan membranes | |
CN104119244A (zh) | 基于功能性纳米通道阵列实现dl酪氨酸的手性拆分及在线检测的方法 | |
CN111545073B (zh) | 一种手性固膜制备方法及其应用 | |
CN104741009B (zh) | 水杨酸分子印迹醋酸纤维素共混膜的制备方法及其应用 | |
Ting | Reverse-phase liquid chromatographic analysis of cephalosporins | |
CN109554826B (zh) | 一种对氨基酸具有高效选择性的纳米电纺膜及其制备方法 | |
CN103736402B (zh) | 一种海藻酸钠手性交联膜及其应用 | |
CN106047963A (zh) | 一种固定化葡萄糖异构酶生产高果糖浆的方法 | |
CN102850204A (zh) | 一种(s)-2-芳基丙酸类非甾体抗炎药的拆分方法 | |
CN112604675B (zh) | 一种偶氮苯二甲酰胺基桥联β-环糊精手性固定相的制备方法及其用途 | |
CN102432495B (zh) | 利用集成膜技术从谷氨酰胺酶或谷氨酰转肽酶转化液中分离、浓缩l-茶氨酸的方法 | |
CN109678752B (zh) | 一种不对称转化合成l-2-氨基丁酰胺盐酸盐的方法 | |
CN207512108U (zh) | 一种l-脯氨酸发酵液的全膜提取设备 | |
CN103446894B (zh) | 万古霉素手性复合膜及其在苯甘氨酸外消旋体拆分中的应用 | |
CN106977478B (zh) | 一种2-(6-羟基-2,3-二氢苯并呋喃-3-基)乙酸甲酯的手性拆分方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200818 |