US20100140172A1 - Optical-Isomer-Separating Agent - Google Patents
Optical-Isomer-Separating Agent Download PDFInfo
- Publication number
- US20100140172A1 US20100140172A1 US11/884,417 US88441706A US2010140172A1 US 20100140172 A1 US20100140172 A1 US 20100140172A1 US 88441706 A US88441706 A US 88441706A US 2010140172 A1 US2010140172 A1 US 2010140172A1
- Authority
- US
- United States
- Prior art keywords
- separating agent
- enantiomeric
- enantiomeric isomer
- organic solvent
- isomer separating
- 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.)
- Abandoned
Links
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 83
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 51
- 239000005017 polysaccharide Substances 0.000 claims abstract description 51
- 239000003960 organic solvent Substances 0.000 claims abstract description 28
- 239000007788 liquid Substances 0.000 claims abstract description 22
- 239000000126 substance Substances 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 239000002245 particle Substances 0.000 claims abstract description 6
- 230000000977 initiatory effect Effects 0.000 claims abstract description 4
- 238000007613 slurry method Methods 0.000 claims abstract description 4
- 150000004676 glycans Chemical class 0.000 claims abstract 7
- 238000000034 method Methods 0.000 claims description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000000741 silica gel Substances 0.000 claims description 18
- 229910002027 silica gel Inorganic materials 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 229920000856 Amylose Polymers 0.000 claims description 9
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- 239000001913 cellulose Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 150000004804 polysaccharides Chemical class 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000011148 porous material Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229920001503 Glucan Polymers 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- -1 acid amide compounds Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229920001221 xylan Polymers 0.000 description 3
- SBTVLCPCSXMWIQ-UHFFFAOYSA-N (3,5-dimethylphenyl) carbamate Chemical compound CC1=CC(C)=CC(OC(N)=O)=C1 SBTVLCPCSXMWIQ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 229920002498 Beta-glucan Polymers 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 229920002558 Curdlan Polymers 0.000 description 2
- 239000001879 Curdlan Substances 0.000 description 2
- 229920002670 Fructan Polymers 0.000 description 2
- 229920001202 Inulin Polymers 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- WQZGKKKJIJFFOK-RWOPYEJCSA-N beta-D-mannose Chemical compound OC[C@H]1O[C@@H](O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-RWOPYEJCSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 235000019316 curdlan Nutrition 0.000 description 2
- 229940078035 curdlan Drugs 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 2
- 229940029339 inulin Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000002444 silanisation Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- WDQLRUYAYXDIFW-RWKIJVEZSA-N (2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-4-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1 WDQLRUYAYXDIFW-RWKIJVEZSA-N 0.000 description 1
- DZSGDHNHQAJZCO-UHFFFAOYSA-N 1-isocyanato-3,5-dimethylbenzene Chemical compound CC1=CC(C)=CC(N=C=O)=C1 DZSGDHNHQAJZCO-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920002305 Schizophyllan Polymers 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001334 alicyclic compounds Chemical class 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 150000002243 furanoses Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 229920005640 poly alpha-1,3-glucan Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/29—Chiral phases
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3833—Chiral chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3268—Macromolecular compounds
- B01J20/3272—Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3268—Macromolecular compounds
- B01J20/328—Polymers on the carrier being further modified
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/50—Conditioning of the sorbent material or stationary liquid
- G01N30/56—Packing methods or coating methods
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/50—Conditioning of the sorbent material or stationary liquid
- G01N30/56—Packing methods or coating methods
- G01N2030/562—Packing methods or coating methods packing
- G01N2030/565—Packing methods or coating methods packing slurry packing
Definitions
- the present invention relates to an enantiomeric isomer separating agent and a method of producing the agent.
- a separating agent obtained by carrying a polysaccharide derivative on silica gel has been generally used as, for example, an enantiomeric resolution agent for high performance liquid chromatography.
- the manners in each of which silica gel supports the polysaccharide derivative are classified into the case where silica gel is caused to support the polysaccharide derivative physically (physical support type separating agent) and the case where silica gel is caused to support the polysaccharide derivative by chemical bonding (chemical support type separating agent). See JP-B-2751004 or JP-A-8-5623.
- the chemical support type separating agent has a smaller amount of eluted component originating from the polysaccharide derivative than that of the physical support type separating agent even when an organic solvent in which the polysaccharide derivative is soluble is used.
- an unreacted polysaccharide derivative is present even in the chemical support type separating agent, so an eluent contains eluted component originating from the polysaccharide derivative.
- JP-A 7-260762 discloses a coating type separating agent having a small amount of eluted component.
- a low-molecular-weight polysaccharide derivative is eluted in such physical support type separating agent. This is because the molecular weight distribution of a polysaccharide to be used varies.
- the present invention provides an enantiomeric isomer separating agent improved in the separating performance when it is used for a separating agent of high performance liquid chromatography and a method of producing the agent.
- the present invention provides an enantiomeric isomer separating agent, which includes a polysaccharide derivative supported on particles of a support by chemical bonding, and has a concentration of eluted component (in terms of mass proportion) as determined through a liquid passing test under the following conditions of 20 ppm or lower:
- the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method
- a method of producing the above-mentioned enantiomeric isomer separating agent including the steps of: washing an unwashed enantiomeric isomer separating agent with an organic solvent in which the polysaccharide derivative is soluble once or multiple times; and drying the washed enantiomeric isomer separating agent.
- a method of separating enantiomeric isomers including bringing the enantiomeric isomers into contact with the above-mentioned enantiomeric isomer separating agent, or use of the above enantiomeric isomer separating agent for separating enantiomeric isomers.
- unwashed enantiomeric isomer separating agent refers to an enantiomeric isomer separating agent that does not satisfy the following requirement: the concentration of eluted component (in terms of mass proportion) upon performance of a liquid passing test under the above-mentioned conditions is 20 ppm or lower.
- An enantiomeric isomer separating agent of the present invention has good separating performance, and can increase the purity of a fractionated enantiomeric isomer.
- the agent is suitable for high performance liquid chromatography.
- the enantiomeric isomer separating agent of the present invention has a concentration of eluted component (in terms of mass proportion) as determined through the following liquid passing test of 20 ppm or lower, preferably 15 ppm or lower, or more preferably 10 ppm or lower.
- the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method
- a chemical support type separating agent is produced by chemically bonding a polysaccharide derivative to a support.
- a polysaccharide derivative to be used in the present invention is well known, and can be produced by applying, for example, Examples 1 to 5 of JP-A-2004-3935, a method described in Synthesis Example 1 of JP-A-7-260762, or a method described in Production Method 3 of paragraph 43 of JP-B-2751004.
- An enantiomeric isomer separating agent obtained by causing a support to support the polysaccharide derivative to be used in the present invention is well known, and can be produced by applying, for example, a method described in Example 1 of JP-B-2751004.
- a porous organic support or a porous inorganic support can be used as the support, and a porous inorganic support is preferable.
- a polymeric substance composed of, for example, polystyrene, polyacrylamide, or polyacrylate can be suitably used in a porous organic support.
- Silica, alumina, magnesia, glass, kaolin, titanium oxide, a silicate, hydroxyapatite, or the like can be suitably used in a porous inorganic support; silica gel is particularly preferable.
- silica gel when silica gel is used, silica gel is desirably subjected to a surface treatment such as a silanization treatment (silanization treatment with an aminoalkylsilane) or a plasma treatment in order that an influence of silanol remaining on the surface of silica gel may be eliminated, and the affinity of silica gel for an enantiomerically active polymer compound may be improved.
- a surface treatment such as a silanization treatment (silanization treatment with an aminoalkylsilane) or a plasma treatment in order that an influence of silanol remaining on the surface of silica gel may be eliminated, and the affinity of silica gel for an enantiomerically active polymer compound may be improved.
- a surface treatment such as a silanization treatment (silanization treatment with an aminoalkylsilane) or a plasma treatment in order that an influence of silanol remaining on the surface of silica gel may be eliminated, and the affinity of silica gel for
- a porous support in particular, silica gel has a particle diameter of preferably 1 to 300 ⁇ m, more preferably 15 to 100 ⁇ m, or still more preferably 20 to 50 ⁇ m, and has an average pore diameter of preferably 200 to 8,000 ⁇ , more preferably 200 to 4,000 ⁇ , or still more preferably 300 to 2,000 ⁇ . It should be noted that the particle diameter of the porous support is substantially the particle diameter of the separating agent.
- the average pore diameter of the porous support preferably falls within the range because a solution of an enantiomerically active polymer compound is sufficiently infiltrated into the pores of the porous support, and the enantiomerically active polymer compound can easily adhere to the inner wall of each of the pores in a uniform fashion. Further, the pressure loss of the separating agent can be maintained at a low level because the pores are prevented from clogging.
- polysaccharide conveying polysaccharide derivative examples include any of a synthetic polysaccharide, a natural polysaccharide, and a natural products-modified polysaccharide as long as the polysaccharide or the derivative thereof is enantiomerically active.
- the polysaccharide or the derivative thereof preferably has a high regularity in bonding manner.
- polysaccharide examples include: ⁇ -1,4-glucan (cellulose); ⁇ -1,4-glucan (amylose or amylopectin); ⁇ -1,6-glucan (dextran); ⁇ -1,6-glucan (pustulan); ⁇ -1,3-glucan (such as curdlan or schizophyllan); ⁇ -1,3-glucan; ⁇ -1,2-glucan (a Crown Gall polysaccharide); ⁇ -1,4-galactan; ⁇ -1,4-mannan; ⁇ -1,6-mannan; ⁇ -1,2-fructan (inulin); ⁇ -2,6-fructan (levan); ⁇ -1,4-xylan; ⁇ -1,3-xylan; ⁇ -1,4-chitosan; ⁇ -1,4-N-acetylchitosan (chitin); pullulan; agarose; and alginic acid. Starch containing amylose is also included.
- cellulose, amylose, ⁇ -1,4-xylan, ⁇ -1,4-chitosan, chitin, ⁇ -1,4-mannan, inulin, curdlan, and the like are preferred because they easily enables highly pure polysaccharides to be obtained.
- Cellulose and amylose are particularly preferred.
- the number average degree of polymerization of the polysaccharide is preferably 5 or more, or more preferably 10 or more, and has no particular upper limit.
- the number average degree of polymerization is preferably 1,000 or less in terms of the easiness for handling, and is more preferably 5 to 1,000, still more preferably 10 to 1,000, or particularly preferably 10 to 500.
- a product obtained by bonding a compound having a functional group capable of reacting with a hydroxyl group to some or all of the hydroxyl groups of the above-mentioned polysaccharide by, for example, ester bonding, urethane bonding or ether bonding can be used as the polysaccharide derivative.
- Examples of functional group-containing compounds that can react with a hydroxyl group include isocyanate derivatives, carboxylic acids, esters, acid halides, acid amide compounds, halides compounds, aldehydes, alcohols or other elimination group-containing compounds; and their aliphatic, alicyclic, aromatic, and heteroaromatic compounds.
- Examples of a particularly preferable polysaccharide derivative include a polysaccharide ester derivative and a polysaccharide carbamate derivative.
- eluted component refers to, for example, a reaction by-product such as an isocyanic acid derivative or carboxylic acid derivative originating from a compound having a functional group capable of reacting with a hydroxyl group, or a polysaccharide derivative that has not been chemically bonded to the support.
- a reaction by-product such as an isocyanic acid derivative or carboxylic acid derivative originating from a compound having a functional group capable of reacting with a hydroxyl group, or a polysaccharide derivative that has not been chemically bonded to the support.
- the enantiomeric isomer separating agent obtained by chemically bonding the polysaccharide derivative to the support is washed with an organic solvent in which the polysaccharide derivative is soluble.
- the washing can be performed once or multiple times (for example, two to ten times).
- a method of washing the unwashed separating agent may be any method with which the unwashed separating agent and the organic solvent can be sufficiently brought into contact with each other, and a column mode, a batch mode, a method involving pouring the organic solvent into a residue after filtration to wash the unwashed separating agent, a heating reflux method, or the like is applicable.
- organic solvent used for washing can be any solvent selected from tetrahydrofuran (THF), acetone, ethyl acetate, chloroform, methylene chloride, dimethyl acetoamide, dimethylformamide (DMF), and methanol.
- THF tetrahydrofuran
- acetone acetone
- ethyl acetate chloroform
- methylene chloride dimethyl acetoamide
- dimethylformamide DMF
- methanol methanol
- the total used amount of the organic solvent is preferably 5 to 100 ml, more preferably 10 to 70 ml, or still more preferably 20 to 40 ml with respect to 1 g of the polysaccharide derivative in the unwashed separating agent.
- the temperature of the organic solvent is lower than the boiling point of the solvent or not lower than the boiling point can be chosen depending on the washing method, and the temperature of the organic solvent is preferably 50 to 150° C., more preferably 60 to 120° C., or still more preferably 70 to 100° C.
- the time needed for washing the unwashed separating agent may be any time required to reduce the amount of eluted component to a predetermined amount or less, and is generally about 1 to 100 hours, or preferably about 1 to 50 hours.
- a filler after the washing can be recovered by, for example, filtration.
- the temperature at which the filler is filtrated is typically 10 to 150° C., or preferably 20 to 100° C.
- the separating agent after the washing is dried.
- a method of drying the separating agent is not particularly limited, and is appropriately selected in consideration of the time period for which the separating agent is subjected to a drying treatment, and a cost for the treatment.
- the separating agent is preferably subjected to a drying treatment under reduced pressure at room temperature to 100° C. for 2 to 24 hours.
- An enantiomeric isomer separating agent obtained by the production method of the present invention has a concentration of eluted component in the above-mentioned liquid passing test of a predetermined value or lower.
- Amylose derivative-bonded silica gel thus obtained was washed with 2.4 L of DMF at 75° C. (24 ml with respect to 1 g of an amylose derivative), whereby a target enantiomeric isomer separating agent was obtained.
- Silica gel the surface of which had been treated with a silane treatment agent having an amino group at any one of its terminals was caused to support cellulose tris(3,5-dimethylphenylcarbamate) produced by a known method (Example 1 of JP-B 2669554) by physical adsorption.
- a predetermined liquid passing test was performed by using the enantiomeric isomer separating agent of the present invention and tetrahydrofuran as a solvent to determine the concentration of eluted component (ppm).
- the M 1 was 416.18 g
- the M 2 was 2.7 mg
- the ratio M 2 /M 1 was 6.5 ppm.
- An unwashed chemical support type enantiomeric isomer separating agent was obtained in the same manner as in Example 1. 100 g of the resultant separating agent were washed by a general washing method. That is, the separating agent was filtrated through a glass filter at room temperature, and was washed with 2.4 L of methanol.
- a liquid passing test of the present invention was performed by using the resultant enantiomeric isomer separating agent and ethyl acetate as a solvent to determine the concentration of eluted component.
- the M 1 was 416.15 g
- the M 2 was 85 mg
- the ratio M 2 /M 1 was 204 ppm.
- An unwashed chemical support type enantiomeric isomer separating agent was obtained in the same manner as in Example 2. 100 g of the resultant separating agent were washed by a general washing method. That is, the separating agent was filtrated through a glass filter at room temperature, and was washed with 2.4 L of methanol.
- a liquid passing test of the present invention was performed by using the resultant enantiomeric isomer separating agent and THF as a solvent to determine the concentration of eluted component.
- the M 1 was 416.23 g
- the M 2 was 203 mg
- the ratio M 2 /M 1 was 488 ppm.
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Abstract
According to the present invention, there is provided an enantiomeric isomer separating agent, which includes a polysaccharide derivative supported by particles of a support by chemical bonding, and has a concentration of eluted component (in terms of mass proportion) as determined through a liquid passing test under the following conditions of 20 ppm or lower: (liquid passing test) (1) the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method, (2) an organic solvent in which the polysaccharide derivative is soluble is used as a solvent, and passing of this solvent whose temperature is set at 40° C. is initiated at a flow rate of 8 ml/min, (3) collection of the solvent passed is initiated 1 hour after the initiation of the liquid passing, the solvent is collected for 1 hour (480 ml), and a mass (M1) of the solvent is measured, and (4) the liquid collected is condensed and dried, a mass (M2) of a residue is measured, and the concentration of eluted component is determined from an expression M2/M1.
Description
- The present invention relates to an enantiomeric isomer separating agent and a method of producing the agent.
- A separating agent obtained by carrying a polysaccharide derivative on silica gel has been generally used as, for example, an enantiomeric resolution agent for high performance liquid chromatography. The manners in each of which silica gel supports the polysaccharide derivative are classified into the case where silica gel is caused to support the polysaccharide derivative physically (physical support type separating agent) and the case where silica gel is caused to support the polysaccharide derivative by chemical bonding (chemical support type separating agent). See JP-B-2751004 or JP-A-8-5623.
- The chemical support type separating agent has a smaller amount of eluted component originating from the polysaccharide derivative than that of the physical support type separating agent even when an organic solvent in which the polysaccharide derivative is soluble is used. However, an unreacted polysaccharide derivative is present even in the chemical support type separating agent, so an eluent contains eluted component originating from the polysaccharide derivative.
- In the case where eluted component originating from, for example, an unreacted polysaccharide derivative is present in an eluent as described above, the following problem arises depending on whether the amount of eluted component is large or small when a separating agent containing such eluted component is used as a separating agent for high performance liquid chromatography: the stability of the baseline of a chromatogram deteriorates, or the purity of a fractionated product cannot be sufficiently increased.
- Investigations have already been conducted on a reduction in amount of eluted component in the physical support type separating agent. JP-A 7-260762 discloses a coating type separating agent having a small amount of eluted component.
- A low-molecular-weight polysaccharide derivative is eluted in such physical support type separating agent. This is because the molecular weight distribution of a polysaccharide to be used varies.
- On the other hand, not only such low-molecular-weight polysaccharide derivative as described above but also a low-molecular-weight or high-molecular-weight polysaccharide derivative that has not been chemically bonded to a support, and, furthermore, an impurity originating from a compound having a functional group capable of reacting with a hydroxyl group of a polysaccharide derivative are eluted in a chemical support type separating agent. As described above, eluted component from a chemical support type polysaccharide derivative is different from that of a physical support type polysaccharide derivative.
- When a conventional chemical support type separating agent is used for a separating agent for high performance liquid chromatography, as described above, it still needs to be improved in terms of prevention of the deterioration of the stability of the baseline of a chromatogram, the stabilization of the quality of a fractionated product, and an improvement in purity of the fractionated product.
- The present invention provides an enantiomeric isomer separating agent improved in the separating performance when it is used for a separating agent of high performance liquid chromatography and a method of producing the agent.
- The present invention provides an enantiomeric isomer separating agent, which includes a polysaccharide derivative supported on particles of a support by chemical bonding, and has a concentration of eluted component (in terms of mass proportion) as determined through a liquid passing test under the following conditions of 20 ppm or lower:
- (Liquid Passing Test)
- (1) the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method,
- (2) an organic solvent in which the polysaccharide derivative is soluble is used as a solvent, and passing of the organic solvent whose temperature is set at 40° C. is initiated at a flow rate of 8 ml/min,
- (3) collection of the organic solvent passed is initiated 1 hour after the initiation of the liquid passing, the organic solvent is collected for 1 hour (480 ml), and a mass (M1) of the organic solvent is measured, and
- (4) the liquid collected is condensed and dried, a mass (M2) of a residue is measured, and the concentration of eluted component is determined from an expression M2/M1.
- According to the present invention, there is provided a method of producing the above-mentioned enantiomeric isomer separating agent, including the steps of: washing an unwashed enantiomeric isomer separating agent with an organic solvent in which the polysaccharide derivative is soluble once or multiple times; and drying the washed enantiomeric isomer separating agent.
- Further, according to the present invention, there is provided a method of separating enantiomeric isomers including bringing the enantiomeric isomers into contact with the above-mentioned enantiomeric isomer separating agent, or use of the above enantiomeric isomer separating agent for separating enantiomeric isomers.
- It should be noted that the term “unwashed enantiomeric isomer separating agent” refers to an enantiomeric isomer separating agent that does not satisfy the following requirement: the concentration of eluted component (in terms of mass proportion) upon performance of a liquid passing test under the above-mentioned conditions is 20 ppm or lower.
- An enantiomeric isomer separating agent of the present invention has good separating performance, and can increase the purity of a fractionated enantiomeric isomer. The agent is suitable for high performance liquid chromatography.
- (Enantiomeric Isomer Separating Agent)
- The enantiomeric isomer separating agent of the present invention has a concentration of eluted component (in terms of mass proportion) as determined through the following liquid passing test of 20 ppm or lower, preferably 15 ppm or lower, or more preferably 10 ppm or lower.
- (Liquid Passing Test)
- (1) the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method,
- (2) an organic solvent in which the polysaccharide derivative is soluble is used as a solvent, and passing of the organic solvent whose temperature is set at 40° C. is initiated at a flow rate of 8 ml/min,
- (3) collection of the organic solvent passed is initiated 1 hour after the initiation of the liquid passing, the organic solvent is collected for 1 hour (480 ml), and a mass (M1) for each fraction of the organic solvent is measured, and
- (4) the liquid collected is condensed and dried, a mass (M2) of a residue is measured, and the concentration of eluted component is determined from an expression M2/M1.
- (Method of Producing Enantiomeric Isomer Separating Agent)
- First, a chemical support type separating agent is produced by chemically bonding a polysaccharide derivative to a support.
- A polysaccharide derivative to be used in the present invention is well known, and can be produced by applying, for example, Examples 1 to 5 of JP-A-2004-3935, a method described in Synthesis Example 1 of JP-A-7-260762, or a method described in Production Method 3 of paragraph 43 of JP-B-2751004.
- An enantiomeric isomer separating agent (unwashed enantiomeric isomer separating agent) obtained by causing a support to support the polysaccharide derivative to be used in the present invention is well known, and can be produced by applying, for example, a method described in Example 1 of JP-B-2751004.
- A porous organic support or a porous inorganic support can be used as the support, and a porous inorganic support is preferable. A polymeric substance composed of, for example, polystyrene, polyacrylamide, or polyacrylate can be suitably used in a porous organic support. Silica, alumina, magnesia, glass, kaolin, titanium oxide, a silicate, hydroxyapatite, or the like can be suitably used in a porous inorganic support; silica gel is particularly preferable.
- It should be noted that, when silica gel is used, silica gel is desirably subjected to a surface treatment such as a silanization treatment (silanization treatment with an aminoalkylsilane) or a plasma treatment in order that an influence of silanol remaining on the surface of silica gel may be eliminated, and the affinity of silica gel for an enantiomerically active polymer compound may be improved. However, no problem arises even when the surface of silica gel is not treated at all.
- A porous support, in particular, silica gel has a particle diameter of preferably 1 to 300 μm, more preferably 15 to 100 μm, or still more preferably 20 to 50 μm, and has an average pore diameter of preferably 200 to 8,000 Å, more preferably 200 to 4,000 Å, or still more preferably 300 to 2,000 Å. It should be noted that the particle diameter of the porous support is substantially the particle diameter of the separating agent.
- The average pore diameter of the porous support preferably falls within the range because a solution of an enantiomerically active polymer compound is sufficiently infiltrated into the pores of the porous support, and the enantiomerically active polymer compound can easily adhere to the inner wall of each of the pores in a uniform fashion. Further, the pressure loss of the separating agent can be maintained at a low level because the pores are prevented from clogging.
- Examples of the polysaccharide conveying polysaccharide derivative include any of a synthetic polysaccharide, a natural polysaccharide, and a natural products-modified polysaccharide as long as the polysaccharide or the derivative thereof is enantiomerically active. However, the polysaccharide or the derivative thereof preferably has a high regularity in bonding manner.
- Examples of the polysaccharide include: β-1,4-glucan (cellulose); α-1,4-glucan (amylose or amylopectin); α-1,6-glucan (dextran); β-1,6-glucan (pustulan); β-1,3-glucan (such as curdlan or schizophyllan); α-1,3-glucan; β-1,2-glucan (a Crown Gall polysaccharide); β-1,4-galactan; β-1,4-mannan; α-1,6-mannan; β-1,2-fructan (inulin); β-2,6-fructan (levan); β-1,4-xylan; β-1,3-xylan; β-1,4-chitosan; α-1,4-N-acetylchitosan (chitin); pullulan; agarose; and alginic acid. Starch containing amylose is also included.
- Of those, cellulose, amylose, β-1,4-xylan, β-1,4-chitosan, chitin, β-1,4-mannan, inulin, curdlan, and the like are preferred because they easily enables highly pure polysaccharides to be obtained. Cellulose and amylose are particularly preferred.
- The number average degree of polymerization of the polysaccharide (average number of pyranose or furanose rings in one molecule) is preferably 5 or more, or more preferably 10 or more, and has no particular upper limit. However, the number average degree of polymerization is preferably 1,000 or less in terms of the easiness for handling, and is more preferably 5 to 1,000, still more preferably 10 to 1,000, or particularly preferably 10 to 500.
- A product obtained by bonding a compound having a functional group capable of reacting with a hydroxyl group to some or all of the hydroxyl groups of the above-mentioned polysaccharide by, for example, ester bonding, urethane bonding or ether bonding can be used as the polysaccharide derivative.
- Examples of functional group-containing compounds that can react with a hydroxyl group include isocyanate derivatives, carboxylic acids, esters, acid halides, acid amide compounds, halides compounds, aldehydes, alcohols or other elimination group-containing compounds; and their aliphatic, alicyclic, aromatic, and heteroaromatic compounds.
- Examples of a particularly preferable polysaccharide derivative include a polysaccharide ester derivative and a polysaccharide carbamate derivative.
- The term “eluted component” as used in the present invention refers to, for example, a reaction by-product such as an isocyanic acid derivative or carboxylic acid derivative originating from a compound having a functional group capable of reacting with a hydroxyl group, or a polysaccharide derivative that has not been chemically bonded to the support.
- Next, the enantiomeric isomer separating agent obtained by chemically bonding the polysaccharide derivative to the support (unwashed enantiomeric isomer separating agent) is washed with an organic solvent in which the polysaccharide derivative is soluble. The washing can be performed once or multiple times (for example, two to ten times).
- A method of washing the unwashed separating agent may be any method with which the unwashed separating agent and the organic solvent can be sufficiently brought into contact with each other, and a column mode, a batch mode, a method involving pouring the organic solvent into a residue after filtration to wash the unwashed separating agent, a heating reflux method, or the like is applicable.
- Examples of organic solvent used for washing can be any solvent selected from tetrahydrofuran (THF), acetone, ethyl acetate, chloroform, methylene chloride, dimethyl acetoamide, dimethylformamide (DMF), and methanol.
- The total used amount of the organic solvent is preferably 5 to 100 ml, more preferably 10 to 70 ml, or still more preferably 20 to 40 ml with respect to 1 g of the polysaccharide derivative in the unwashed separating agent.
- Whether the temperature of the organic solvent is lower than the boiling point of the solvent or not lower than the boiling point can be chosen depending on the washing method, and the temperature of the organic solvent is preferably 50 to 150° C., more preferably 60 to 120° C., or still more preferably 70 to 100° C.
- The time needed for washing the unwashed separating agent may be any time required to reduce the amount of eluted component to a predetermined amount or less, and is generally about 1 to 100 hours, or preferably about 1 to 50 hours.
- A filler after the washing can be recovered by, for example, filtration. The temperature at which the filler is filtrated is typically 10 to 150° C., or preferably 20 to 100° C.
- Next, the separating agent after the washing is dried. A method of drying the separating agent is not particularly limited, and is appropriately selected in consideration of the time period for which the separating agent is subjected to a drying treatment, and a cost for the treatment. However, the separating agent is preferably subjected to a drying treatment under reduced pressure at room temperature to 100° C. for 2 to 24 hours.
- An enantiomeric isomer separating agent obtained by the production method of the present invention has a concentration of eluted component in the above-mentioned liquid passing test of a predetermined value or lower. As a result, when the enantiomeric isomer separating agent of the present invention is used as a filler for high performance liquid chromatography to separate enantiomeric isomers, nearly no unreacted polysaccharide derivative is eluted, so the baseline of a chromatogram at the time of fractionation is stabilized, and the purity of a fractionated product can be increased. Accordingly, a high-quality enantiomerically resoluble substance can be stably supplied.
- (i) Synthesis of Amylose-Bonded Silica Gel
- Under a nitrogen atmosphere, 100 g of silica gel the surface of which had been treated with a siliane treatment agent having an amino group at any one of its terminals and 20 g of amylose were dispersed in 380 ml of DMSO at 70° C. A borane-pyridine complex and acetic acid were added to the dispersion, and the whole was stirred for 20 hours. The stirred mixture was separated by filtration, and the residue was washed with methanol, DMSO, and methanol in the stated order. After that, the residue was dried in a vacuum, whereby amylose-bonded silica gel was obtained.
- (ii) Synthesis of enantiomeric isomer separating agent in which hydroxyl group of amylose is turned into 3,5-dimethylphenylcarbamate
- Under a nitrogen atmosphere, 100 g of amylose-bonded silica gel, 3 g of 4-dimethylaminopyridine, 300 ml of DMF, and 45 g of 3,5-dimethylphenylisocyanate were dispersed, and the dispersion was stirred at 75° C. for 24 hours.
- Amylose derivative-bonded silica gel thus obtained was washed with 2.4 L of DMF at 75° C. (24 ml with respect to 1 g of an amylose derivative), whereby a target enantiomeric isomer separating agent was obtained.
- (iii) A predetermined liquid passing test was performed by using the enantiomeric isomer separating agent of the present invention and ethyl acetate as a solvent to determine the concentration of eluted component (ppm). As a result, the M1 was 416.08 g, the M2 was 1.2 mg, and the ratio M2/M1 was 3 ppm.
- Silica gel the surface of which had been treated with a silane treatment agent having an amino group at any one of its terminals was caused to support cellulose tris(3,5-dimethylphenylcarbamate) produced by a known method (Example 1 of JP-B 2669554) by physical adsorption.
- 150 g of the resultant separating agent (ratio at which a polymer was supported: 20 wt %) were suspended in 3 L of the mixed solvent of water and acetonitrile, and the suspension was stirred. The suspension was irradiated with UV for 220 minutes by a method described in Example 12 of JP 11-510193 A so that crosslinking might take place. After that, the resultant solid was taken by filtration, repeatedly washed with tetrahydrofuran under heat and reflux 4 times, and dried in a vacuum, whereby a target enantiomeric isomer separating agent was obtained.
- A predetermined liquid passing test was performed by using the enantiomeric isomer separating agent of the present invention and tetrahydrofuran as a solvent to determine the concentration of eluted component (ppm). As a result, the M1 was 416.18 g, the M2 was 2.7 mg, and the ratio M2/M1 was 6.5 ppm.
- An unwashed chemical support type enantiomeric isomer separating agent was obtained in the same manner as in Example 1. 100 g of the resultant separating agent were washed by a general washing method. That is, the separating agent was filtrated through a glass filter at room temperature, and was washed with 2.4 L of methanol.
- A liquid passing test of the present invention was performed by using the resultant enantiomeric isomer separating agent and ethyl acetate as a solvent to determine the concentration of eluted component. The M1 was 416.15 g, the M2 was 85 mg, and the ratio M2/M1 was 204 ppm.
- An unwashed chemical support type enantiomeric isomer separating agent was obtained in the same manner as in Example 2. 100 g of the resultant separating agent were washed by a general washing method. That is, the separating agent was filtrated through a glass filter at room temperature, and was washed with 2.4 L of methanol.
- A liquid passing test of the present invention was performed by using the resultant enantiomeric isomer separating agent and THF as a solvent to determine the concentration of eluted component. The M1 was 416.23 g, the M2 was 203 mg, and the ratio M2/M1 was 488 ppm.
Claims (9)
1. An enantiomeric isomer separating agent, which comprises a polysaccharide derivative supported by particles of a support by chemical bonding, and has a concentration of eluted component (in terms of mass proportion) as determined through a liquid passing test under the following conditions of 20 ppm or lower:
(liquid passing test)
(1) the enantiomeric isomer separating agent is packed into a column having a diameter of 1 cm and a length of 25 cm by a slurry method,
(2) an organic solvent in which the polysaccharide derivative is soluble is used as a solvent, and passing of the organic solvent whose temperature is set at 40° C. is initiated at a flow rate of 8 ml/min,
(3) collection of the organic solvent passed is initiated 1 hour after the initiation of the liquid passing, the organic solvent is collected for 1 hour (480 ml), and a mass (M1) of the organic solvent is measured, and
(4) the liquid collected is condensed and dried, a mass (M2) of a residue is measured, and the concentration of eluted component is determined from an expression M2/M1.
2. The enantiomeric isomer separating agent according to claim 1 , wherein the polysaccharide derivative is a cellulose derivative or an amylose derivative and the support is silica gel.
3. A method of producing the enantiomeric isomer separating agent according to claim 1 , comprising the steps of:
washing an unwashed enantiomeric isomer separating agent with an organic solvent in which the polysaccharide derivative is soluble once or multiple times; and
drying the washed enantiomeric isomer separating agent.
4. The method of producing the enantiomeric isomer separating agent according to claim 3 , wherein the total of the used organic solvent is 5 to 100 ml with respect to 1 g of the polysaccharide derivative in the enantiomeric isomer separating agent.
5. The method of producing the enantiomeric isomer separating agent according to claim 3 , wherein the organic solvent used for the washing step is selected from the group consisting of tetrahydrofuran, acetone, ethyl acetate, chloroform, methylene chloride, dimethylacetamide and dimethylformamide.
6. A method of separating enantiomeric isomers, comprising bringing enantiomeric isomers into contact with the enantiomeric isomer separating agent according to claim 1 .
7. The method according to claim 6 , wherein the separation is performed by high performance liquid chromatography.
8. Use of the enantiomeric isomer separating agent according to claim 1 for separating enantiomeric isomers.
9. The use according to claim 8 , wherein the enantiomeric isomer separating agent is used in high performance liquid chromatography.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2005101846 | 2005-03-31 | ||
JP2005-101846 | 2005-03-31 | ||
PCT/JP2006/307259 WO2006107081A1 (en) | 2005-03-31 | 2006-03-30 | Optical-isomer-separating agent |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2006/307259 A-371-Of-International WO2006107081A1 (en) | 2005-03-31 | 2006-03-30 | Optical-isomer-separating agent |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/199,249 Continuation US8679346B2 (en) | 2005-03-31 | 2011-08-24 | Optical-isomer-separating agent |
Publications (1)
Publication Number | Publication Date |
---|---|
US20100140172A1 true US20100140172A1 (en) | 2010-06-10 |
Family
ID=37073616
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/884,417 Abandoned US20100140172A1 (en) | 2005-03-31 | 2006-03-30 | Optical-Isomer-Separating Agent |
US13/199,249 Expired - Fee Related US8679346B2 (en) | 2005-03-31 | 2011-08-24 | Optical-isomer-separating agent |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/199,249 Expired - Fee Related US8679346B2 (en) | 2005-03-31 | 2011-08-24 | Optical-isomer-separating agent |
Country Status (5)
Country | Link |
---|---|
US (2) | US20100140172A1 (en) |
EP (1) | EP1865313B8 (en) |
JP (1) | JP4871861B2 (en) |
CN (1) | CN101151529B (en) |
WO (1) | WO2006107081A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111366538B (en) * | 2020-03-17 | 2023-06-23 | 江苏道宁药业有限公司 | Method and device for accurately detecting proportion of optical rotamers in polysaccharide containing glucose groups |
CN115792064B (en) * | 2022-11-30 | 2024-06-04 | 东北大学 | Wood chromatographic column for on-line separation and detection of enantiomers and preparation and use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5679572A (en) * | 1993-09-22 | 1997-10-21 | Daicel Chemical Industries, Ltd. | Separation of chiral compounds on polysaccharide supports |
US5736259A (en) * | 1994-03-17 | 1998-04-07 | Daicel Chemical Industries, Ltd. | Packing material for high-performance liquid chromatography and process for producing the same |
US20030192829A1 (en) * | 2002-04-12 | 2003-10-16 | Atsushi Ohnishi | Filler for separation of enantiomeric isomers in simulated moving bed chromatography |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2669554B2 (en) * | 1989-01-20 | 1997-10-29 | ダイセル化学工業株式会社 | Novel polysaccharide derivatives and separating agents |
JP3272354B2 (en) * | 1991-02-28 | 2002-04-08 | ダイセル化学工業株式会社 | Novel polysaccharide derivatives and separating agents |
JPH05255129A (en) * | 1992-03-12 | 1993-10-05 | Nakano Vinegar Co Ltd | Separating agent |
US5496937A (en) * | 1993-05-14 | 1996-03-05 | Nakano Vinegar Co., Ltd. | Polysaccharide substances, process for producing them and use of them |
JP3190206B2 (en) * | 1993-06-22 | 2001-07-23 | ダイセル化学工業株式会社 | Separating agent for optical isomers and method for producing the same |
JP2751004B2 (en) | 1993-09-22 | 1998-05-18 | ダイセル化学工業株式会社 | Novel polysaccharide derivative, its production method and its use |
FR2714671B1 (en) * | 1994-01-05 | 1996-03-15 | Conservatoire Nal Arts Metiers | New polysaccharide derivatives and their use for the preparation of stationary chiral phases useful for the separation of isomers of chemical compounds. |
JP3478595B2 (en) * | 1994-05-17 | 2003-12-15 | ダイセル化学工業株式会社 | Separating agent for optical isomers |
JP3181788B2 (en) | 1994-06-17 | 2001-07-03 | 株式会社ワイエムシィ | Separating agents for chromatography |
CN1099592C (en) * | 1994-07-07 | 2003-01-22 | 大赛璐化学工业株式会社 | Separating agent |
TW362100B (en) | 1995-07-21 | 1999-06-21 | Novartis Ag | The preparation and use of photochemically cross-linked polysaccharide derivatives having no photopolymerisable functional groups |
JP4320068B2 (en) * | 1997-10-03 | 2009-08-26 | ダイセル化学工業株式会社 | Separating agent for optical isomers and process for producing the same |
EP1422521A4 (en) * | 2001-06-15 | 2008-05-07 | Daicel Chem | Separatory agent for optical isomer |
JP2005017268A (en) * | 2003-05-30 | 2005-01-20 | Daicel Chem Ind Ltd | Separating agent for optical isomers, method of manufacturing the same, and separation column for optical isomers |
KR20060124720A (en) * | 2004-03-04 | 2006-12-05 | 다이셀 가가꾸 고교 가부시끼가이샤 | Separating agent for enantiomeric isomer |
-
2006
- 2006-03-30 EP EP06731207.4A patent/EP1865313B8/en not_active Not-in-force
- 2006-03-30 WO PCT/JP2006/307259 patent/WO2006107081A1/en active Application Filing
- 2006-03-30 JP JP2007511254A patent/JP4871861B2/en not_active Expired - Fee Related
- 2006-03-30 CN CN2006800101542A patent/CN101151529B/en not_active Expired - Fee Related
- 2006-03-30 US US11/884,417 patent/US20100140172A1/en not_active Abandoned
-
2011
- 2011-08-24 US US13/199,249 patent/US8679346B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5679572A (en) * | 1993-09-22 | 1997-10-21 | Daicel Chemical Industries, Ltd. | Separation of chiral compounds on polysaccharide supports |
US5736259A (en) * | 1994-03-17 | 1998-04-07 | Daicel Chemical Industries, Ltd. | Packing material for high-performance liquid chromatography and process for producing the same |
US20030192829A1 (en) * | 2002-04-12 | 2003-10-16 | Atsushi Ohnishi | Filler for separation of enantiomeric isomers in simulated moving bed chromatography |
Also Published As
Publication number | Publication date |
---|---|
JP4871861B2 (en) | 2012-02-08 |
US8679346B2 (en) | 2014-03-25 |
EP1865313B1 (en) | 2015-03-25 |
JPWO2006107081A1 (en) | 2008-09-25 |
EP1865313B8 (en) | 2015-05-27 |
CN101151529B (en) | 2011-12-07 |
EP1865313A4 (en) | 2009-01-21 |
US20110313146A1 (en) | 2011-12-22 |
CN101151529A (en) | 2008-03-26 |
WO2006107081A1 (en) | 2006-10-12 |
EP1865313A1 (en) | 2007-12-12 |
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Legal Events
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AS | Assignment |
Owner name: DAICEL CHEMICAL INDUSTRIES, LTD.,JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:KAGAMIHARA, YASUHIRO;REEL/FRAME:024086/0362 Effective date: 20070726 |
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STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |