JPH0552821B2 - - Google Patents
Info
- Publication number
- JPH0552821B2 JPH0552821B2 JP62503117A JP50311787A JPH0552821B2 JP H0552821 B2 JPH0552821 B2 JP H0552821B2 JP 62503117 A JP62503117 A JP 62503117A JP 50311787 A JP50311787 A JP 50311787A JP H0552821 B2 JPH0552821 B2 JP H0552821B2
- Authority
- JP
- Japan
- Prior art keywords
- reagent
- amino
- reagents
- resolution
- reaction
- 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 - Lifetime
Links
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 46
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 19
- 150000001875 compounds Chemical class 0.000 abstract description 17
- 238000000926 separation method Methods 0.000 abstract description 17
- 238000001212 derivatisation Methods 0.000 abstract description 13
- 239000012069 chiral reagent Substances 0.000 abstract description 10
- -1 succinimidyl group Chemical group 0.000 abstract description 8
- 150000004657 carbamic acid derivatives Chemical class 0.000 abstract description 7
- 125000000217 alkyl group Chemical group 0.000 abstract description 5
- 238000004811 liquid chromatography Methods 0.000 abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 5
- 229910052736 halogen Inorganic materials 0.000 abstract description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 abstract description 4
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 22
- 235000001014 amino acid Nutrition 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- 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 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 230000005526 G1 to G0 transition Effects 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 230000006340 racemization Effects 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- LGFDQZCUDVWAIQ-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=C(OC)C=C1 LGFDQZCUDVWAIQ-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 3
- 150000002367 halogens Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 3
- 238000002798 spectrophotometry method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YSCDFPXLCCWBIS-UHFFFAOYSA-N 1-(9h-fluoren-9-yl)ethanol Chemical compound C1=CC=C2C(C(O)C)C3=CC=CC=C3C2=C1 YSCDFPXLCCWBIS-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical group [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-GSVOUGTGSA-N D-glutamine Chemical compound OC(=O)[C@H](N)CCC(N)=O ZDXPYRJPNDTMRX-GSVOUGTGSA-N 0.000 description 2
- 229930195715 D-glutamine Natural products 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 150000002337 glycosamines Chemical class 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 2
- 229960002237 metoprolol Drugs 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- PAXWODJTHKJQDZ-VHSXEESVSA-N (1r,4s)-1,7,7-trimethyl-2-oxo-3-oxabicyclo[2.2.1]heptane-4-carbonyl chloride Chemical compound C1C[C@]2(C(Cl)=O)OC(=O)[C@@]1(C)C2(C)C PAXWODJTHKJQDZ-VHSXEESVSA-N 0.000 description 1
- ATVFTGTXIUDKIZ-YFKPBYRVSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-sulfanylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CS)C(O)=O ATVFTGTXIUDKIZ-YFKPBYRVSA-N 0.000 description 1
- SFRVOKMRHPQYGE-UHFFFAOYSA-N 1-(9h-fluoren-9-yl)ethyl carbonochloridate Chemical compound C1=CC=C2C(C(OC(Cl)=O)C)C3=CC=CC=C3C2=C1 SFRVOKMRHPQYGE-UHFFFAOYSA-N 0.000 description 1
- LRVQJCQTPOUJNW-UHFFFAOYSA-N 2-(9h-fluoren-9-yl)ethyl carbonochloridate Chemical compound C1=CC=C2C(CCOC(=O)Cl)C3=CC=CC=C3C2=C1 LRVQJCQTPOUJNW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 238000003436 Schotten-Baumann reaction Methods 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 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
- 239000012042 active reagent Substances 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 210000003918 fraction a Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002518 isoindoles Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 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
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N βâMercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/96—Esters of carbonic or haloformic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Description
è«æ±ã®ç¯å²
ïŒ æ¬¡ã®äžè¬åŒ
ïŒåŒäžãã¯ããã²ã³ãã¢ãžãåºããŸãã¯ã¹ã¯ã·
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããå åŠæŽ»æ§è©Šè¬ãã
ã¢ããå®èœåºããã€ååç©ãå«ãè©Šæã«ãåœè©²å
åç©ã®ã¢ããå®èœåºãèªå°äœã«å€ãããžã¢ã¹ãã¬
ãªããŒã«ã«ããã³é žå¡©èªå°äœã圢æããããã«æ·»
å ããã€ãã§åœè©²èªå°äœãåé¢ã枬å®ããããšã
ç¹åŸŽãšãããæ°Žæ§ãŸãã¯éæ°Žæ§è©Šæäžã®ã¢ããå®
èœåºããã€ååç©ã®åå²ããã³æž¬å®æ³ã ïŒ ïŒ²ãã¡ãã«åºã§ããããšãç¹åŸŽãšããè«æ±ã®
ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ïŒžãå¡©çŽ ã§ããè«æ±ã®ç¯å²ç¬¬ïŒé ãŸãã¯ç¬¬ïŒ
é ã®æ¹æ³ã ïŒ èªå°äœã®åé¢ããã³æž¬å®äžåŠšå®³ããªãçæç©
ãçããã¢ãã³ãšéå°ã®è©Šè¬ãšãåå¿ãããããš
ãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ããšãã°ã¢ããç³ãŸãã¯ã¢ããé žã®ããã«èŠª
æ°Žæ§ã¢ããèªå°äœã圢æãããå Žåãéå°ã®è©Šè¬
ãäœæ¥µæ§ã®æº¶å€ãããšãã°ãã³ã¿ã³ãŸãã¯ãããµ
ã³ã§æœåºããŠé€ãããšãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬
ïŒé ã®æ¹æ³ã ïŒ åé¢ããã³æž¬å®åŸãã¢ããå®èœåºããã€åå
ç©ãåçããããšãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬ïŒé
ã®æ¹æ³ã ïŒ æ¬¡ã®äžè¬åŒ ïŒåŒäžãã¯ããã²ã³ãã¢ãžãåºããŸãã¯ã¹ã¯ã·
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããååç©ã ïŒ ïŒžãå¡©çŽ ã§ããããšãç¹åŸŽãšããè«æ±ã®ç¯å²
第ïŒé ã®ååç©ã ïŒ ïŒ²ãã¡ãã«åºã§ããããšãç¹åŸŽãšããè«æ±ã®
ç¯å²ç¬¬ïŒé ãŸãã¯ç¬¬ïŒé ã®ååç©ã çºæã®èæ¯ æ¬çºæã¯ãã©ã«è©Šè¬ããã³é«é液äœã¯ãããã°
ã©ãã€ãŒïŒHPLCïŒã«ãã察æäœã®åé¢ãšæ€åºã®
æ¹è¯ã«é¢ãããããã«è©³ããã¯ãæ¬çºæã¯ç¬¬äžçŽ
ããã³ç¬¬äºçŽã¢ãã³ãšåå¿ããŠå®å®ãªãžã¢ã¹ãã¬
ãªããŒã«ã«ããã³é žå¡©ãå®éçã«åœ¢æããå åŠæŽ»
æ§ã¯ããã®é žãã«ãªã¬ãã«ã«é¢ããããã®çæç©
ã¯HPLCã«ã©ã ã§åé¢åŸãè¢å åæãŸãã¯åžå å
床æ³ã«ããæ€åºã§ããã å åŠæŽ»æ§ã¢ããå«æç©è³ªã®åé¢ã¯çç©åŠç 究ã
ãã³è¬ååŠã«ãããŠèããéèŠã§ããããããã®
ç©è³ªã¯è¬å€ã«ãããŠã¯éäŸã®ãã®ã§ããã®å€ãã¯
ã©ã»ãæ··åç©ãšããŠååšãã察æäœã§ãããå€ã
ã®å Žåãããã察æäœã®çç©åŠç掻æ§ã¯äžã€ã®ç¹
å®ã®å åŠæŽ»æ§å¯Ÿæäœã®ç«äœé 座ã«åž°ãããããã
ãæ 察æäœãèå¥ãŸãã¯åå²ããããšãéåžžã«é
èŠã§ããã ã¯ãããã°ã©ãã€ãŒæ³ã¯å°éã®è©Šæãç°¡åãªå
åŠçãæ€åºã®é«æ床ã®ãããªå€ãã®å©ç¹ãäžãã
ãããå®éç®çã«äœ¿çšãããã ããŒããŒã¯ãããã°ã©ãã€ãŒã«ãã1951幎ã®å
åŠæŽ»æ§ç°æ§äœã®æåã®ã¯ãããã°ã©ãã€ãŒåé¢ä»¥
æ¥ãå€æ°ã®ãã®ãããªæ¹æ³ãå°å ¥ãããŠãããæ
è¿æ¬ã«ç·æ¬ãããŠããïŒR.W.ãµãŠã¿ãŒèâç«äœ
ç°æ§äœã®ã¯ãããã°ã©ãã€ãŒåé¢âïŒCRCãã¬
ã¹ããã³ããŒã¬ã³ã1985幎ããã³J.ãžã€ã¯ã¹ãïŒ
A.ã³ã¬ãããïŒS.H.ã¯ã€ã¬ã³å ±èâ察æäœãã©ã»
ãååç©ãããã³åå²âïŒãžãšãŒã³ã»ã¯ã€ãªãŒã»
ã¢ã³ããµã³ãºïŒããŠãŒãšãŒã¯ïŒ1981幎ïŒã 察æäœã®åå²ã¯ãã©ã«è©Šè¬ã®ä»åšãå¿ èŠãšã
ããã¯ãããã°ã©ãã€ãŒåå²æ³ã¯äºã€ã®äž»æ¹åã«
çºéããŠããã ïŒ ãã©ã«åºå®çžïŒCSPïŒãŸãã¯ç§»åçžäžã®ãã©
ã«æåã«ããã«ã©ã ã§ã®å¯Ÿæäœã®çŽæ¥åå²ã ïŒ ãã©ã«è©Šè¬ã§èªå°äœåœ¢æåŸçæãžã¢ã¹ãã¬ãª
ããŒã®éæ¥åå²ã ãã©ã«åºå®çžã§ã®å¯Ÿæäœã®æ¶²äœã¯ãããã°ã©ã
ã€ãŒã«ããçŽæ¥åé¢ã¯å€ãã®æ³šç®ãéããŠããã
çŸåšå¹Ÿã€ãã®åæ¥äžå©çšã§ãããã©ã«ã«ã©ã ãã
ããã§ããã ãå€ãã®ç°ãªãåã®ãã©ã«ç©è³ªãå
é¢ã§ãããã©ã«åºå®çžãã€ããã®ã«åªåãåãã
ããŠããããã§ããªããäºåã«èªå°äœåœ¢æãªãã«
ã©ã®åã®ãã©ã«ã«ã©ã ã§ãçŽæ¥åå²ãããã¢ãã³
ããã³ã¢ããé žã¯ããå°ãªãã ã¿ã¡ã¬ã€çïŒJ.Lig.Chromatographyl 1979幎ã
ïŒå·»ã1229é ïŒã¯ãã©ã«è©Šè¬ã§èªå°äœåœ¢æããé
åžžã®ã«ã©ã ã§åå²ããããžã¢ã¹ãã¬ãªããŒã圢æ
ããããšã«ãã察æäœã®éæ¥åå²ã«åºã¥ãæ¹æ³ã
ç·æ¬ããŠããããã«ã«ã¯çïŒChem.Pharm.
Bull.1975幎ã23å·»ã1623é ïŒã¯ãã©ã«è©Šè¬ãšã
ãŠå®¹æã«å ¥æã§ããå¡©åïŒïŒïŒâ10âã·ãšãŠããŠ
ã¹ã«ããã«ã䜿ã察æäœã¢ããé žã®åé¢ãæåã«
è¡ã€ããã€ãã§ã«ã«ããã«æ®åºã®ç¬¬ïŒå·¥çšã§ïœâ
ããããã³ãžã«ãšã¹ãã«ã«å€æãããšçŽ«å€ç·æ€åº
ã«ææãªèªå°äœãçæããã éžæçã¢ãã³å®èœåºèªå°äœåœ¢æã«æãæ®éã®ã
ã©ã«è©Šè¬ã¯ã第äžçŽããã³ç¬¬äºçŽã¢ãã³ãšåå¿ã
ãŠçŽ«å€ç·ã«ææãªããªå°¿çŽ èªå°äœãäžããã€ãœã
ãªã·ã¢ããŒãã«åºã¥ããã®ã§ãããåå¿ã¯åŒ±å¡©åº
æ§æ¡ä»¶ã§çŽ20å宀枩ã§ãå¯çç©ã®çæãªãã«è¡ã
ããã ãã®çš®ã®æãæåããè©Šè¬ã¯ãã¢ããé žããã³
ã¢ãã³ã®äž¡è ã«äœ¿ããããïŒïŒïŒïŒïŒïŒïŒâãã
ã©ââã¢ã»ãã«âïœâïœâã°ã«ã³ãã©ãã·ã«ã€
ãœããªã·ã¢ããŒãïŒGITCïŒã§ããã倧éšåã®è
çœè³ªã¢ããé žããçæããããªå°¿çŽ èªå°äœã¯ãé
åžžã®éçžã«ã©ã ã§ïŒæé以å ã«åå²ããããåŸã
ããåå²ã¯ãç«äœé 座çåæ§ãšé¢é£ããç³æ®åºã®
芪油æ§ã«ãããã®ãšèããã¹ãã§ãããã ã¢ããå«æååç©ã«å¯Ÿããè¢å ãã©ã«èªå°äœåœ¢
æè©Šè¬ã¯çšã§ããããã©ã«ããªãŒã«ãšçµåãã
âãã¿ã«ã¢ã«ãããïŒOPAïŒã«åºã¥ãè©Šè¬ã®ã¿
ãå ±åãããŠãããïŒæ¥æ¬ç¹èš±60â38652ïŒ85â
38652ïŒã䜿ãããåçš®ã®ãã©ã«ããªãŒã«ååç©ã¯
âã¢ã»ãã«ââã¹ã·ãã€ã³ãBOCââã·
ã¹ãã€ã³ã§ãããããã¹ãŠã¯ç¬¬äžçŽã¢ããåºãšå
å¿ããŠãžã¢ã¹ãã¬ãªããŒã€ãœã€ã³ããŒã«ã圢æã
ããåå¿ã¯éžæçã§ãã©ã»ãåããããšãªãç·©è¡
æ°Žæ§æ··å液äžçŽæ¥å®€æž©ã§ïŒå以å ã«å®çµãããã
ãããçæãžã¢ã¹ãã¬ãªããŒã¯å®å®ã§ã¯ãªãã ãã®ãããªè©Šè¬ããã€ã¹ã幟ã€ãã®å¿ é ã§æãŸ
ããæ¡ä»¶ã¯æ¬¡ã®éãã§ããã ïŒè©Šè¬ã¯å åŠçã«çŽç²ã§ãªããã°ãªããªãã ïŒè©Šè¬ã¯çºè²å£ãŸãã¯çºè¢å å£ãå«ãã§ããªãã
ã°ãªããªãã ïŒåå¿æ¡ä»¶ã¯æž©åã§ããã¹ãã§ããããªããšæœåš
çã©ã»ãåã®å±éºãå¢ãã ïŒè©Šè¬ã¯ç¬¬äžçŽããã³ç¬¬äºçŽã¢ããåºãšåå¿ãã¹
ãã§ããã ïŒçæãžã¢ã¹ãã¬ãªããŒã¯å®å®ã§ãªããã°ãªããª
ãã ïŒçæãžã¢ã¹ãã¬ãªããŒã¯éåžžã®HPLCã«ã©ã äž
ã§åé¢ãããå¿ èŠãããã ïŒæ¹æ³ã¯ååèŠæš¡ã§å¿çšã§ããå¿ èŠãããã ïŒæ¹æ³ã¯èªååã§ããå¿ èŠãããã ãããã第äžããã³ç¬¬äºã¢ããå«æååç©ã®ã©
ã»ãæ··åç©ãå¹æçã«èªå°äœã«å€ããæ€åºããå
é¢ããæ¹æ³ãšçµåãããããã©ã«è©Šè¬ããããŸã§
ã«é瀺ãŸãã¯ç€ºåãããããšã¯ãªãã çºæã®èŠçŽ æ¬çºæã®ç®çã¯ãéåžžã®éçžHPLCã«ã©ã ã§ç¬¬
äžçŽããã³ç¬¬äºçŽã¢ããå«æååç©ãéæ¥åå²ã
ãããã®ãã©ã«è©Šè¬ãšæ¹æ³ãæäŸããã«ãããåœ
該詊è¬ã¯ãå®å®ã§æ¶²äœã¯ãããã°ã©ãã€ãŒã«ãã
åé¢åŸè¢å åæãŸãã¯åžå å 床æ³ã§æ€åºã§ããè¢
å èªå°äœãäžããã¹ãã§ãããå®å®ãªèªå°äœã¯å®
éåãšèªååã容æã«ãããããã«ãåå¿ã¯æž©å
ãªæ¡ä»¶äžãæ°Žçžäžã§ã©ã»ãåãªãè¿ éã«èµ·ãã¹ã
ã§ããã 次ã®äžè¬åŒ ïŒåŒäžãã¯ããã²ã³ãã¢ãžãåºããŸãã¯ã¹ã¯ã·
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããå åŠæŽ»æ§è©Šè¬ãæ·»
å ããããšã«ããåœè©²ååç©ã®ã¢ããå®èœåºãèª
å°äœã«å€ãããžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ã
圢æããããšã«ãããäžèšãéæã§ããäžèšã«ã«
ããã³é žå¡©ã¯æ¶²äœã¯ãããã°ã©ãã€ãŒã«ããåé¢
åŸãæ¢ç¥ã®æ¹æ³ããšãã°è¢å åæãŸãã¯åžå å 床
æ³ã«ãã枬å®ãããã æ¬è©Šè¬ã¯æ¬¡ã®ããšãå®è¡ããïŒ ïŒ åå²ããã¢ãã³ããã³ã¢ããé žã®å åŠçŽåºŠã®
枬å®ã ïŒ çç©ç³»äžã«çš®ã ã®éã§å«ãŸãã察æäœã¢ãã
å«æååç©ã®æž¬å®ã ïŒ ã¢ããå«æã©ã»ãæ··åç©ã®ååçåå²ã å³ã®èª¬æ 第ïŒå³ã¯è©Šè¬ããã³åå¿åŒã瀺ãã 第ïŒå³ã¯çš®ã ã®ã¢ããé žã®è¢å ãžã¢ã¹ãã¬ãªã
ãŒã«ã«ããã³é žå¡©ã圢æããåå¿é床ãšåçã瀺
ãã°ã©ãã§ããã 第ïŒå³ã¯ã¢ã¹ãã©ã®ã³é žãšã°ã«ã¿ãã³é žã«ã€ã
ãŠåå¿åç察PHã瀺ãã°ã©ãã§ããã 第ïŒå³ã¯éçžæ¶²äœã¯ãããã°ã©ãã€ãŒã§è¡ã€ã
è¢å æšèãããžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ãš
ããŠã®17çš®ã®ã¢ããé žã®åå²ã瀺ãã¯ãããã°ã©
ã ã§ããã 第ïŒå³ã¯ã©ã»ãã¡ãããããŒã«ã®åå²ã瀺ãã¯
ãããã°ã©ã ã§ããã 第ïŒå³ã¯åžè²©ã®âå åŠçã«çŽç²ãªââã°ã«ã¿
ãã³èªå°äœåœ¢æãšåå²ã瀺ãã¯ãããã°ã©ã ã§ã
ãã çºæã®èª¬æ æ¬çºæã¯ãã·ãšããã³âããŠãã³æ¡ä»¶äžã§ã¯ã
ãã®é žå¡©ãšçš®ã ã®ã¢ãã³ãšãè¿ éã«åå¿ããå®å®
ãªã«ã«ããã³é žå¡©ã圢æããããšã«åºã¥ããã®ã§
ãããåå¿ã¯ïŒå·¥çšã§å®€æž©ã§æ°ç§ä»¥å ã«éè¡ãã
ããããPHç¯å²ã§ã¯ãåå¿ã¯ã¢ããå®èœåºã«å¯Ÿã
éžæçã§ãå¯äžã®çæå¯çç©ã¯çžåœããã¢ã«ã³ãŒ
ã«ã§ãããéå°ã®è©Šè¬ã¯å®¹æã«åŠçãããã®ã§æ¬¡
ã®åé¢å·¥çšã§ã®åŠšå®³ãã¯ã¶ããã ã¯ããã®é žïŒâãã«ãªã¬ãã«ã¡ãã«è©Šè¬
ïŒFMOCïŒã¯ãå±èµ·çºå æ³¢é·270ïŒ315nïœãæã
ãè¢å äœã§ããããããã€ãŠçæç©ã¯ãã®æ³¢é·ã®
çµåãã§éžæçã«æ€åºãããããã®æ§è³ªãéžæç
åå¿ãšçµåãããšããè€éãªæ··åç©ããšãã°äœæ¶²
ïŒbody fluidsïŒãæµåãŸãã¯ååŠçæäœãªãã«å
æ±ããããã«ãªãã æ¬çºæã®ç®çã¯ãã©ã»ãã¢ããå«æååç©ãšå
å¿ããŠãžã¢ã¹ãã¬ãªããŒã圢æããããã«ãå€ã
ã®å©ç¹ããã€ãŠã¢ãã©ã«FMOCè©Šè¬ãšåäžæ¹æ³
ã§äœ¿çšã§ããå åŠæŽ»æ§è©Šè¬ãåæããããšã§ã
ãã該ãžã¢ã¹ãã¬ãªããŒã¯ãéåžžã®åé¢ç³»ãå žå
çã«ã¯ãçè·¡åæããã³åååé¢çšã®æãæ®éãª
æå¹ãªLCåé¢ç³»ã§ããéçžHPLCã§åå²å¯èœã§
ããã¹ãã§ãããè©Šè¬ãå åŠæŽ»æ§ã«ããããšã¯ã
åå²å¯èœãªãžã¢ã¹ãã¬ãªããŒãåŸãããšã®ä¿èšŒãš
ã¯ãªããªããäžæççŽ ååã®å°å ¥ã¯ãè©Šè¬ã®æ§è³ª
ãç¶æãããããªäœçœ®ã§å®æœããå¿ èŠãããã æ¬çºæã¯ïŒâãã«ãªã¬ãã«âïŒâäœçœ®ã«äžæç
çŽ ååãå°å ¥ããããšã«ãããFMOCè©Šè¬ã®ã
ã©ãªãã€ãŒãã€ããåºãããšã§ãã€ãããã®åã®
ååç©ã¯åŸæ¥æç®ã«èšèŒãããŠããªãããã®äœçœ®
ã¯çæã¢ããå®èœåºããã³ãã«ãªã¬ã³éšåãè¡šã
ãåæ§ã®ç°ç¶é 眮ã«è¿ãããéèŠã§ãããããã
ã¯ãžã¢ã¹ãã¬ãªããŒã®æåçåå²ãåãæããã©
ã«è©Šè¬ãèšèšããäžè¬èŠåã§ã¯ãªãããšãææã
ãŠããå¿ èŠãããããããã€ãŠãäºèšãè¡ãããš
ã¯äžå¯èœãªã®ã§ãå åŠåå²ã¯ãªãè©Šè¡é¯èª€çå®éš
ã«åºã¥ããŠãããããããé©ãããšã«ãã¯ããã®
é žïŒâãã«ãªã¬ãã«âïŒâãšãã«è©Šè¬ïŒFLECïŒ
ã¯å€ãã®ã¢ãã³ãšåå¿ããŠéçžLCã«ã©ã ã§åå²
å¯èœãªãžã¢ã¹ãã¬ãªããŒãçæãããããã«ã¯ã
ãã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšãã«
ã¯ãäž»ãšããŠååšããâ圢ã®åã«åé¢ãããåž
ã«ååšããâã¢ããé žã®ãžã¢ã¹ãã¬ãªããŒãäž
ããçæ³çã«åŸ®éå®éã§ãããæ°è©Šè¬ã®æ§è³ªã¯ã¢
ãã©ã«FMOCè©Šè¬ã«å¹æµããŠç¶æããããæåŸ
ã«è€éãªæ··åç©äžã®å åŠæŽ»æ§ã¢ããå«æååç©ã®
枬å®ããã³ã¢ãã³ã®åååå²ã«èããå®éçã§æ
çšãªæ°èŠè©Šè¬ãèšèŒããã FLECãšã¢ããé žãšã®åå¿ã¯ç¬¬ïŒå³ã«ç€ºããã
ãã«é²ãããã®è©Šè¬ã¯ãŸãæ°Žãšåå¿ããå æ°Žå解
çæç©ãšããŠçžåœããã¢ã«ã³ãŒã«ãçæããã ã¯ããã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãš
ãã«ïŒFLECïŒã®åæ ïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšã¿ããŒã«ã®åæïŒ ä¹Ÿç¥ãšãŒãã«100mläžã®ãã«ãªã¬ã³8.3ïœã®æº¶æ¶²
ã«ãBuLiïŒãããµã³äž1.6MïŒ31mlãæ·»å ããã
æ··åç©ã30åéæµããã€ãã§æ°·æµŽã§å·ãããçæ
æ··åç©ã«ã也ç¥ãšãŒãã«40mläžã®ã¢ã»ãã¢ã«ãã
ã2.8mlã®æº¶æ¶²ã15åã§å ããïŒæééæµããã
æ°Ž100mlãå ãããšãŒãã«å±€ãå液濟æã§éãã
也ç¥ïŒMgSO4ïŒããèžçºããããçæç©ããã©
ãã·ãŠã¯ãããã°ã©ãã€ã§ããã«ç²Ÿè£œãããªã°ã
ã€ã³ïŒæ²žç¹80ã110âïŒã§åçµæ¶ããçœè²éç¶æ¶
ãåŸããèç¹101ã103âã質éã¹ãã¯ãã«
M+mïŒe210.151HNMRïŒCDCl3ïŒã0.87ïŒäºéç·ã
3HïŒã1.70ïŒäžéç·ã1HïŒã4.09ïŒäºéç·ã1HïŒã
4.35ã4.65ïŒå€éç·ã1HïŒã7.15ã7.85ïŒå€éç·ã
8HïŒã ïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšã¿ããŒã«ã®å åŠå
å² ç¡æ°Žããªãžã³25mläžã®ïŒâïŒïŒâãã«ãªã¬ãã«ïŒ
ãšã¿ããŒã«4.0ïœã®æº¶æ¶²ã«ãïŒâïŒâã«ã³ãã¢ã³é ž
å¡©åç©ã®çã¢ã«é4.12ïœãæ·»å ããæ··åç©ã宀枩
ã§ïŒæéãããŸããã溶液ãæ°·æ°Žã«ããã
CH2Cl2ã§æœåºãããCH2Cl2ãåžå¡©é žã§æŽã也ç¥
ïŒMgSO4ïŒããèžçºä¹Ÿåºãããç²ãšã¹ãã«ãã¡ã¿
ããŒã«ïŒMeOHïŒ200mlã«æº¶ããâ15âã«å·ããã
æåºçµæ¶ïŒç»åïŒâãåäžæº¶åªããïŒåçµæ¶å
ãã溶解æ§ã®å°ãããžã¢ã¹ãã¬ãªããŒãšã¹ãã«
1.0ïœãçŽç²åœ¢ã§åŸãïŒèç¹159ã160âïŒãïŒã©ã»
ãååç©ã®èç¹152âïŒããã®ãžã¢ã¹ãã¬ãªããŒãš
ã¹ãã«ã®å åŠçŽåºŠã¯ãã©ã«åºå®çžïŒ»ã¢ããããã
ã«ã·ãªã«ã«çµåããïŒâïŒâãžããããã³ãŸã€ã«
ããšãã«ã°ãªã·ã³ãããŒã¯ã«çžïŒœã§æ€æ»ãã99ïŒ
ã§ãã€ãã äžèšãšã¹ãã«ã®å æ°Žå解 也ç¥ãšãŒãã«50mläžã®å åŠçãªçŽç²ãªãžã¢ã¹ã
ã¬ãªããŒãšã¹ãã«1.0ïœã®æº¶æ¶²ã«ãLiAlH40.8ïœã
å ãããæ··åç©ã宀枩ã§ïŒæéãããŸããåŸåŠç
åŸã¢ã«ã³ãŒã«ãåŸããèç¹91ã93âå解ïŒã ã¯ããã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãš
ãã« ïŒâã«å·ãã也ç¥ãã«ãšã³15mläžã®ãã¹ã²ã³
ïŒ0.8ïœã8.1ïœmolïŒã®æº¶æ¶²ã«ã也ç¥ãã«ãšã³20ml
äžã®å åŠçã«çŽç²ãªã¢ã«ã³ãŒã«ïŒ0.44ïœã2.1ïœ
molïŒãšããªãšãã«ã¢ãã³ïŒ0.30mlã2.1ïœmolïŒ
ã®æº¶æ¶²ã滎äžãããæ·»å å®äºåŸãïŒâã§ïŒæéæ¹
æãç¶ãã次ãã§ããªãšãã«ã¢ãã³å¡©é žå¡©ãæ¿Ÿé
ã§é€ãã濟液ãæžå§ã§æ¿çž®ããæ²¹ãåŸãã α25ïŒïŒ67.9°ïŒCH2Cl2ãïŒïŒïŒ α25/578ïŒïŒ70.5°ïŒCH2Cl2ãïŒïŒïŒ1 HNMRïŒCDCl3ïŒïŒ0.76ïŒäºéç·ã3HïŒã4.30ïŒäº
éç·ã1HïŒã5.47ã5.75ïŒå€éç·ã1HïŒ7.18ã
7.75ïŒå€éç·ã8HïŒ åæC16H13O2Clãšã㊠èšç®å€ïŒïŒ£ã70.46ïŒïŒšã4.80ïŒClã13.00 å®æž¬å€ïŒïŒ£ã70.64ïŒïŒšã4.80ïŒClã13.3 å®éšæ¡ä»¶ 溶å€ãšè©Šè¬ïŒ ã¢ã»ããããªã«ãããã©ããããã©ã³ããã³ã¢
ã»ãã³ã¯ã©ã¹ããŒã³ïŒãŠãªãŒã«ãŒããŒã³ãè±ïŒã
ãè³Œå ¥ãããã¢ããé žæšæºããã³FMOCâClè©Š
è¬ã¯ã·ã°ãïŒã»ã³ãã»ã«ã€ã¹ã»ããºãŒãªå·ãç±³ïŒ
ããåŸãã溶åºç·©è¡æ¶²ã¯ïŒåéã®èžæºæ°Žã«æº¶ãã
ãé ¢é žããã€ããïŒïŒmlïŒïŒãæ°Žé žåãããªãŠ
ã ã§é©åœãªPHã«æ»Žå®ãããFLECâClè©Šè¬ã¯ã¢ã»
ããããªã«ïŒã¢ã»ãã³ïŒïŒïŒïŒïŒã«æº¶ããã15ïœ
molïŒã®æ¿åºŠã§ãã€ããåå¿ç·©è¡æ¶²ã¯ããŠé ž
ïŒ1MïŒããäœããPHãæ°Žé žåãããªãŠã ã§èª¿ç¯ã
ãã èªå°äœåœ¢æïŒ è©ŠæïŒ0.4mlãšç·©è¡æ¶²ïŒ0.1mlãPHïŒãïŒmlã®å
å¿ã¬ã©ã¹ã³ãã§æ··åãããè©Šè¬ïŒ0.5mlïŒãå ãã
åå¿ããããïŒååŸã¬ã©ã¹ç¶ããã³ã¿ã³ã§ã»ãšã
ã©å ãããåå¿æ··åç©ãæœåºãéå°ã®è©Šè¬ãé€
ããæœåºãïŒåããè¿ããšãæ°Žçžã¯æ³šå ¥ã«ãã䜿
ããã åå¿éåºŠïŒ ã¢ããé žãšFLECâClè©Šè¬ãšã®åå¿é床ã第ïŒ
å³ã«ç€ºããããã¯PH8.03ïŒè©Šæãã©ã¹ç·©è¡æ¶²ïŒã§
è©Šè¬ã«ããåžžæ³ã§ã¢ããé žã®èªå°äœåœ¢æïŒäžåºŠã«
äžã€ïŒã«ãã枬å®ãããããæéééåŸãé ¢é žã
æ·»å ããŠåå¿ãæ¢ããã³ã¿ã³æœåºã«ããFLECâ
Clè©Šè¬ã®éå°ãé€ãããæªåå¿ã§æ®ã€ãéã¯ã
âãã¿ã«ã¢ã«ãããïŒã¡ã«ã«ãããšã¿ããŒã«ã§ã«
ã©ã åèªå°äœåœ¢æãã€ãã§æ¶²äœã¯ãããã°ã©ãã€
ãŒã«ãã枬å®ãããçµæããåäžæ¹æ³ã ãFLEC
âClè©Šè¬ãªãã«ïŒã¢ããé žã®æåã®éïŒåŠçãã
溶液ãšæ¯èŒããããããFLECâèªå°äœãžã®è»¢å
çãèšç®ããããåç¹ã¯ïŒåã®æž¬å®ã®å¹³åã§ã
ãã ã¢ã¹ãã©ã®ã³é žããã³ã°ã«ã¿ãã³é žã®åå¿é床
ã«å¯ŸããPHã®åœ±é¿ã第ïŒå³ã«ç€ºããïŒåã®åå¿æ
éã§äžèšãšåäžæ¹æ³ã§å®æœãããPH8.01ã8.46ã
9.01ã9.47ããã³10.23ã§æž¬å®ãããPHã¯ç·©è¡æ¶²æ·»
å åŸã®åå¿æº¶æ¶²ã§æž¬å®ããã FLECâClãã³FMOCâClè©Šè¬ãšããªã³ãã°ã¿
ã¿ãã³é žããããªã³ããªãžã³ãšã®çžå¯Ÿåå¿é床
ã¯ãæšæºã¢ããé žæº¶æ¶²ãè©Šè¬ã®åã ã§èªå°äœã«å€
ãããšãåŸãããåçãšãæ··åFLECïŒFMOCè©Š
è¬ã䜿ã€ããšãã®çµæãšãæ¯èŒããããšã«ãã決
å®ãããèªå°äœãã¯ãããã°ã©ãã€ãŒã§åé¢ãã
ããŒã¯é¢ç©ãæ¯èŒããã 第ïŒå³ã«ãéçžæ¶²äœã¯ãããã°ã©ãã€ãŒã§ä»¶ãª
ã€ãè¢å æšæºãžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ãš
ããŠã®17çš®ã®ã¢ãã³é žã®åå²ã瀺ãã å®éšæ¡ä»¶ïŒ FLECâClè©Šè¬ãã¢ã»ããããªã«ïŒã¢ã»ãã³
ïŒ1/4ïŒã15ïœïŒã«æº¶ãããåå¿ç·©è¡æ¶²ã¯ããŠé žå¡©
ç·©è¡æ¶²ã1MãPH6.5ã§ããã è©Šæ0.4mlãšããŠé žå¡©ç·©è¡æ¶²0.1mlãæ··åããã
ãã®æº¶æ¶²ã«è©Šæ0.5mlãå ãããïŒåã®åå¿æé
åŸãæ··åç©ããã³ã¿ã³ã§ïŒåæœåºããããã³ã¿ã³
æœåºç©ãæšãŠãæ°Žçžã¯æ³šå ¥ã«ãã䜿ãããé žåºã
ãããªãæ¯èŒççæ°Žæ§ã¢ãã³ã®èªå°äœåœ¢æã®ãšã
ã¯ãæœåºå·¥çšãã¯ã¶ãã芪氎æ§ã¢ãã³ãå žåçã«
ã¯ããããã·ãããªã³ãŸãã¯ããã©ãžã³ãšã®åå¿
ã«ããéå°ã®è©Šè¬ãé€å»ããã
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããå åŠæŽ»æ§è©Šè¬ãã
ã¢ããå®èœåºããã€ååç©ãå«ãè©Šæã«ãåœè©²å
åç©ã®ã¢ããå®èœåºãèªå°äœã«å€ãããžã¢ã¹ãã¬
ãªããŒã«ã«ããã³é žå¡©èªå°äœã圢æããããã«æ·»
å ããã€ãã§åœè©²èªå°äœãåé¢ã枬å®ããããšã
ç¹åŸŽãšãããæ°Žæ§ãŸãã¯éæ°Žæ§è©Šæäžã®ã¢ããå®
èœåºããã€ååç©ã®åå²ããã³æž¬å®æ³ã ïŒ ïŒ²ãã¡ãã«åºã§ããããšãç¹åŸŽãšããè«æ±ã®
ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ïŒžãå¡©çŽ ã§ããè«æ±ã®ç¯å²ç¬¬ïŒé ãŸãã¯ç¬¬ïŒ
é ã®æ¹æ³ã ïŒ èªå°äœã®åé¢ããã³æž¬å®äžåŠšå®³ããªãçæç©
ãçããã¢ãã³ãšéå°ã®è©Šè¬ãšãåå¿ãããããš
ãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬ïŒé ã®æ¹æ³ã ïŒ ããšãã°ã¢ããç³ãŸãã¯ã¢ããé žã®ããã«èŠª
æ°Žæ§ã¢ããèªå°äœã圢æãããå Žåãéå°ã®è©Šè¬
ãäœæ¥µæ§ã®æº¶å€ãããšãã°ãã³ã¿ã³ãŸãã¯ãããµ
ã³ã§æœåºããŠé€ãããšãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬
ïŒé ã®æ¹æ³ã ïŒ åé¢ããã³æž¬å®åŸãã¢ããå®èœåºããã€åå
ç©ãåçããããšãç¹åŸŽãšããè«æ±ã®ç¯å²ç¬¬ïŒé
ã®æ¹æ³ã ïŒ æ¬¡ã®äžè¬åŒ ïŒåŒäžãã¯ããã²ã³ãã¢ãžãåºããŸãã¯ã¹ã¯ã·
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããååç©ã ïŒ ïŒžãå¡©çŽ ã§ããããšãç¹åŸŽãšããè«æ±ã®ç¯å²
第ïŒé ã®ååç©ã ïŒ ïŒ²ãã¡ãã«åºã§ããããšãç¹åŸŽãšããè«æ±ã®
ç¯å²ç¬¬ïŒé ãŸãã¯ç¬¬ïŒé ã®ååç©ã çºæã®èæ¯ æ¬çºæã¯ãã©ã«è©Šè¬ããã³é«é液äœã¯ãããã°
ã©ãã€ãŒïŒHPLCïŒã«ãã察æäœã®åé¢ãšæ€åºã®
æ¹è¯ã«é¢ãããããã«è©³ããã¯ãæ¬çºæã¯ç¬¬äžçŽ
ããã³ç¬¬äºçŽã¢ãã³ãšåå¿ããŠå®å®ãªãžã¢ã¹ãã¬
ãªããŒã«ã«ããã³é žå¡©ãå®éçã«åœ¢æããå åŠæŽ»
æ§ã¯ããã®é žãã«ãªã¬ãã«ã«é¢ããããã®çæç©
ã¯HPLCã«ã©ã ã§åé¢åŸãè¢å åæãŸãã¯åžå å
床æ³ã«ããæ€åºã§ããã å åŠæŽ»æ§ã¢ããå«æç©è³ªã®åé¢ã¯çç©åŠç 究ã
ãã³è¬ååŠã«ãããŠèããéèŠã§ããããããã®
ç©è³ªã¯è¬å€ã«ãããŠã¯éäŸã®ãã®ã§ããã®å€ãã¯
ã©ã»ãæ··åç©ãšããŠååšãã察æäœã§ãããå€ã
ã®å Žåãããã察æäœã®çç©åŠç掻æ§ã¯äžã€ã®ç¹
å®ã®å åŠæŽ»æ§å¯Ÿæäœã®ç«äœé 座ã«åž°ãããããã
ãæ 察æäœãèå¥ãŸãã¯åå²ããããšãéåžžã«é
èŠã§ããã ã¯ãããã°ã©ãã€ãŒæ³ã¯å°éã®è©Šæãç°¡åãªå
åŠçãæ€åºã®é«æ床ã®ãããªå€ãã®å©ç¹ãäžãã
ãããå®éç®çã«äœ¿çšãããã ããŒããŒã¯ãããã°ã©ãã€ãŒã«ãã1951幎ã®å
åŠæŽ»æ§ç°æ§äœã®æåã®ã¯ãããã°ã©ãã€ãŒåé¢ä»¥
æ¥ãå€æ°ã®ãã®ãããªæ¹æ³ãå°å ¥ãããŠãããæ
è¿æ¬ã«ç·æ¬ãããŠããïŒR.W.ãµãŠã¿ãŒèâç«äœ
ç°æ§äœã®ã¯ãããã°ã©ãã€ãŒåé¢âïŒCRCãã¬
ã¹ããã³ããŒã¬ã³ã1985幎ããã³J.ãžã€ã¯ã¹ãïŒ
A.ã³ã¬ãããïŒS.H.ã¯ã€ã¬ã³å ±èâ察æäœãã©ã»
ãååç©ãããã³åå²âïŒãžãšãŒã³ã»ã¯ã€ãªãŒã»
ã¢ã³ããµã³ãºïŒããŠãŒãšãŒã¯ïŒ1981幎ïŒã 察æäœã®åå²ã¯ãã©ã«è©Šè¬ã®ä»åšãå¿ èŠãšã
ããã¯ãããã°ã©ãã€ãŒåå²æ³ã¯äºã€ã®äž»æ¹åã«
çºéããŠããã ïŒ ãã©ã«åºå®çžïŒCSPïŒãŸãã¯ç§»åçžäžã®ãã©
ã«æåã«ããã«ã©ã ã§ã®å¯Ÿæäœã®çŽæ¥åå²ã ïŒ ãã©ã«è©Šè¬ã§èªå°äœåœ¢æåŸçæãžã¢ã¹ãã¬ãª
ããŒã®éæ¥åå²ã ãã©ã«åºå®çžã§ã®å¯Ÿæäœã®æ¶²äœã¯ãããã°ã©ã
ã€ãŒã«ããçŽæ¥åé¢ã¯å€ãã®æ³šç®ãéããŠããã
çŸåšå¹Ÿã€ãã®åæ¥äžå©çšã§ãããã©ã«ã«ã©ã ãã
ããã§ããã ãå€ãã®ç°ãªãåã®ãã©ã«ç©è³ªãå
é¢ã§ãããã©ã«åºå®çžãã€ããã®ã«åªåãåãã
ããŠããããã§ããªããäºåã«èªå°äœåœ¢æãªãã«
ã©ã®åã®ãã©ã«ã«ã©ã ã§ãçŽæ¥åå²ãããã¢ãã³
ããã³ã¢ããé žã¯ããå°ãªãã ã¿ã¡ã¬ã€çïŒJ.Lig.Chromatographyl 1979幎ã
ïŒå·»ã1229é ïŒã¯ãã©ã«è©Šè¬ã§èªå°äœåœ¢æããé
åžžã®ã«ã©ã ã§åå²ããããžã¢ã¹ãã¬ãªããŒã圢æ
ããããšã«ãã察æäœã®éæ¥åå²ã«åºã¥ãæ¹æ³ã
ç·æ¬ããŠããããã«ã«ã¯çïŒChem.Pharm.
Bull.1975幎ã23å·»ã1623é ïŒã¯ãã©ã«è©Šè¬ãšã
ãŠå®¹æã«å ¥æã§ããå¡©åïŒïŒïŒâ10âã·ãšãŠããŠ
ã¹ã«ããã«ã䜿ã察æäœã¢ããé žã®åé¢ãæåã«
è¡ã€ããã€ãã§ã«ã«ããã«æ®åºã®ç¬¬ïŒå·¥çšã§ïœâ
ããããã³ãžã«ãšã¹ãã«ã«å€æãããšçŽ«å€ç·æ€åº
ã«ææãªèªå°äœãçæããã éžæçã¢ãã³å®èœåºèªå°äœåœ¢æã«æãæ®éã®ã
ã©ã«è©Šè¬ã¯ã第äžçŽããã³ç¬¬äºçŽã¢ãã³ãšåå¿ã
ãŠçŽ«å€ç·ã«ææãªããªå°¿çŽ èªå°äœãäžããã€ãœã
ãªã·ã¢ããŒãã«åºã¥ããã®ã§ãããåå¿ã¯åŒ±å¡©åº
æ§æ¡ä»¶ã§çŽ20å宀枩ã§ãå¯çç©ã®çæãªãã«è¡ã
ããã ãã®çš®ã®æãæåããè©Šè¬ã¯ãã¢ããé žããã³
ã¢ãã³ã®äž¡è ã«äœ¿ããããïŒïŒïŒïŒïŒïŒïŒâãã
ã©ââã¢ã»ãã«âïœâïœâã°ã«ã³ãã©ãã·ã«ã€
ãœããªã·ã¢ããŒãïŒGITCïŒã§ããã倧éšåã®è
çœè³ªã¢ããé žããçæããããªå°¿çŽ èªå°äœã¯ãé
åžžã®éçžã«ã©ã ã§ïŒæé以å ã«åå²ããããåŸã
ããåå²ã¯ãç«äœé 座çåæ§ãšé¢é£ããç³æ®åºã®
芪油æ§ã«ãããã®ãšèããã¹ãã§ãããã ã¢ããå«æååç©ã«å¯Ÿããè¢å ãã©ã«èªå°äœåœ¢
æè©Šè¬ã¯çšã§ããããã©ã«ããªãŒã«ãšçµåãã
âãã¿ã«ã¢ã«ãããïŒOPAïŒã«åºã¥ãè©Šè¬ã®ã¿
ãå ±åãããŠãããïŒæ¥æ¬ç¹èš±60â38652ïŒ85â
38652ïŒã䜿ãããåçš®ã®ãã©ã«ããªãŒã«ååç©ã¯
âã¢ã»ãã«ââã¹ã·ãã€ã³ãBOCââã·
ã¹ãã€ã³ã§ãããããã¹ãŠã¯ç¬¬äžçŽã¢ããåºãšå
å¿ããŠãžã¢ã¹ãã¬ãªããŒã€ãœã€ã³ããŒã«ã圢æã
ããåå¿ã¯éžæçã§ãã©ã»ãåããããšãªãç·©è¡
æ°Žæ§æ··å液äžçŽæ¥å®€æž©ã§ïŒå以å ã«å®çµãããã
ãããçæãžã¢ã¹ãã¬ãªããŒã¯å®å®ã§ã¯ãªãã ãã®ãããªè©Šè¬ããã€ã¹ã幟ã€ãã®å¿ é ã§æãŸ
ããæ¡ä»¶ã¯æ¬¡ã®éãã§ããã ïŒè©Šè¬ã¯å åŠçã«çŽç²ã§ãªããã°ãªããªãã ïŒè©Šè¬ã¯çºè²å£ãŸãã¯çºè¢å å£ãå«ãã§ããªãã
ã°ãªããªãã ïŒåå¿æ¡ä»¶ã¯æž©åã§ããã¹ãã§ããããªããšæœåš
çã©ã»ãåã®å±éºãå¢ãã ïŒè©Šè¬ã¯ç¬¬äžçŽããã³ç¬¬äºçŽã¢ããåºãšåå¿ãã¹
ãã§ããã ïŒçæãžã¢ã¹ãã¬ãªããŒã¯å®å®ã§ãªããã°ãªããª
ãã ïŒçæãžã¢ã¹ãã¬ãªããŒã¯éåžžã®HPLCã«ã©ã äž
ã§åé¢ãããå¿ èŠãããã ïŒæ¹æ³ã¯ååèŠæš¡ã§å¿çšã§ããå¿ èŠãããã ïŒæ¹æ³ã¯èªååã§ããå¿ èŠãããã ãããã第äžããã³ç¬¬äºã¢ããå«æååç©ã®ã©
ã»ãæ··åç©ãå¹æçã«èªå°äœã«å€ããæ€åºããå
é¢ããæ¹æ³ãšçµåãããããã©ã«è©Šè¬ããããŸã§
ã«é瀺ãŸãã¯ç€ºåãããããšã¯ãªãã çºæã®èŠçŽ æ¬çºæã®ç®çã¯ãéåžžã®éçžHPLCã«ã©ã ã§ç¬¬
äžçŽããã³ç¬¬äºçŽã¢ããå«æååç©ãéæ¥åå²ã
ãããã®ãã©ã«è©Šè¬ãšæ¹æ³ãæäŸããã«ãããåœ
該詊è¬ã¯ãå®å®ã§æ¶²äœã¯ãããã°ã©ãã€ãŒã«ãã
åé¢åŸè¢å åæãŸãã¯åžå å 床æ³ã§æ€åºã§ããè¢
å èªå°äœãäžããã¹ãã§ãããå®å®ãªèªå°äœã¯å®
éåãšèªååã容æã«ãããããã«ãåå¿ã¯æž©å
ãªæ¡ä»¶äžãæ°Žçžäžã§ã©ã»ãåãªãè¿ éã«èµ·ãã¹ã
ã§ããã 次ã®äžè¬åŒ ïŒåŒäžãã¯ããã²ã³ãã¢ãžãåºããŸãã¯ã¹ã¯ã·
ã³ã€ããžã«åºã§ãã¯ã¢ã«ãã«åºãŸãã¯ããªãã«
ãªãã¡ãã«åºã§ããïŒãæããå åŠæŽ»æ§è©Šè¬ãæ·»
å ããããšã«ããåœè©²ååç©ã®ã¢ããå®èœåºãèª
å°äœã«å€ãããžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ã
圢æããããšã«ãããäžèšãéæã§ããäžèšã«ã«
ããã³é žå¡©ã¯æ¶²äœã¯ãããã°ã©ãã€ãŒã«ããåé¢
åŸãæ¢ç¥ã®æ¹æ³ããšãã°è¢å åæãŸãã¯åžå å 床
æ³ã«ãã枬å®ãããã æ¬è©Šè¬ã¯æ¬¡ã®ããšãå®è¡ããïŒ ïŒ åå²ããã¢ãã³ããã³ã¢ããé žã®å åŠçŽåºŠã®
枬å®ã ïŒ çç©ç³»äžã«çš®ã ã®éã§å«ãŸãã察æäœã¢ãã
å«æååç©ã®æž¬å®ã ïŒ ã¢ããå«æã©ã»ãæ··åç©ã®ååçåå²ã å³ã®èª¬æ 第ïŒå³ã¯è©Šè¬ããã³åå¿åŒã瀺ãã 第ïŒå³ã¯çš®ã ã®ã¢ããé žã®è¢å ãžã¢ã¹ãã¬ãªã
ãŒã«ã«ããã³é žå¡©ã圢æããåå¿é床ãšåçã瀺
ãã°ã©ãã§ããã 第ïŒå³ã¯ã¢ã¹ãã©ã®ã³é žãšã°ã«ã¿ãã³é žã«ã€ã
ãŠåå¿åç察PHã瀺ãã°ã©ãã§ããã 第ïŒå³ã¯éçžæ¶²äœã¯ãããã°ã©ãã€ãŒã§è¡ã€ã
è¢å æšèãããžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ãš
ããŠã®17çš®ã®ã¢ããé žã®åå²ã瀺ãã¯ãããã°ã©
ã ã§ããã 第ïŒå³ã¯ã©ã»ãã¡ãããããŒã«ã®åå²ã瀺ãã¯
ãããã°ã©ã ã§ããã 第ïŒå³ã¯åžè²©ã®âå åŠçã«çŽç²ãªââã°ã«ã¿
ãã³èªå°äœåœ¢æãšåå²ã瀺ãã¯ãããã°ã©ã ã§ã
ãã çºæã®èª¬æ æ¬çºæã¯ãã·ãšããã³âããŠãã³æ¡ä»¶äžã§ã¯ã
ãã®é žå¡©ãšçš®ã ã®ã¢ãã³ãšãè¿ éã«åå¿ããå®å®
ãªã«ã«ããã³é žå¡©ã圢æããããšã«åºã¥ããã®ã§
ãããåå¿ã¯ïŒå·¥çšã§å®€æž©ã§æ°ç§ä»¥å ã«éè¡ãã
ããããPHç¯å²ã§ã¯ãåå¿ã¯ã¢ããå®èœåºã«å¯Ÿã
éžæçã§ãå¯äžã®çæå¯çç©ã¯çžåœããã¢ã«ã³ãŒ
ã«ã§ãããéå°ã®è©Šè¬ã¯å®¹æã«åŠçãããã®ã§æ¬¡
ã®åé¢å·¥çšã§ã®åŠšå®³ãã¯ã¶ããã ã¯ããã®é žïŒâãã«ãªã¬ãã«ã¡ãã«è©Šè¬
ïŒFMOCïŒã¯ãå±èµ·çºå æ³¢é·270ïŒ315nïœãæã
ãè¢å äœã§ããããããã€ãŠçæç©ã¯ãã®æ³¢é·ã®
çµåãã§éžæçã«æ€åºãããããã®æ§è³ªãéžæç
åå¿ãšçµåãããšããè€éãªæ··åç©ããšãã°äœæ¶²
ïŒbody fluidsïŒãæµåãŸãã¯ååŠçæäœãªãã«å
æ±ããããã«ãªãã æ¬çºæã®ç®çã¯ãã©ã»ãã¢ããå«æååç©ãšå
å¿ããŠãžã¢ã¹ãã¬ãªããŒã圢æããããã«ãå€ã
ã®å©ç¹ããã€ãŠã¢ãã©ã«FMOCè©Šè¬ãšåäžæ¹æ³
ã§äœ¿çšã§ããå åŠæŽ»æ§è©Šè¬ãåæããããšã§ã
ãã該ãžã¢ã¹ãã¬ãªããŒã¯ãéåžžã®åé¢ç³»ãå žå
çã«ã¯ãçè·¡åæããã³åååé¢çšã®æãæ®éãª
æå¹ãªLCåé¢ç³»ã§ããéçžHPLCã§åå²å¯èœã§
ããã¹ãã§ãããè©Šè¬ãå åŠæŽ»æ§ã«ããããšã¯ã
åå²å¯èœãªãžã¢ã¹ãã¬ãªããŒãåŸãããšã®ä¿èšŒãš
ã¯ãªããªããäžæççŽ ååã®å°å ¥ã¯ãè©Šè¬ã®æ§è³ª
ãç¶æãããããªäœçœ®ã§å®æœããå¿ èŠãããã æ¬çºæã¯ïŒâãã«ãªã¬ãã«âïŒâäœçœ®ã«äžæç
çŽ ååãå°å ¥ããããšã«ãããFMOCè©Šè¬ã®ã
ã©ãªãã€ãŒãã€ããåºãããšã§ãã€ãããã®åã®
ååç©ã¯åŸæ¥æç®ã«èšèŒãããŠããªãããã®äœçœ®
ã¯çæã¢ããå®èœåºããã³ãã«ãªã¬ã³éšåãè¡šã
ãåæ§ã®ç°ç¶é 眮ã«è¿ãããéèŠã§ãããããã
ã¯ãžã¢ã¹ãã¬ãªããŒã®æåçåå²ãåãæããã©
ã«è©Šè¬ãèšèšããäžè¬èŠåã§ã¯ãªãããšãææã
ãŠããå¿ èŠãããããããã€ãŠãäºèšãè¡ãããš
ã¯äžå¯èœãªã®ã§ãå åŠåå²ã¯ãªãè©Šè¡é¯èª€çå®éš
ã«åºã¥ããŠãããããããé©ãããšã«ãã¯ããã®
é žïŒâãã«ãªã¬ãã«âïŒâãšãã«è©Šè¬ïŒFLECïŒ
ã¯å€ãã®ã¢ãã³ãšåå¿ããŠéçžLCã«ã©ã ã§åå²
å¯èœãªãžã¢ã¹ãã¬ãªããŒãçæãããããã«ã¯ã
ãã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšãã«
ã¯ãäž»ãšããŠååšããâ圢ã®åã«åé¢ãããåž
ã«ååšããâã¢ããé žã®ãžã¢ã¹ãã¬ãªããŒãäž
ããçæ³çã«åŸ®éå®éã§ãããæ°è©Šè¬ã®æ§è³ªã¯ã¢
ãã©ã«FMOCè©Šè¬ã«å¹æµããŠç¶æããããæåŸ
ã«è€éãªæ··åç©äžã®å åŠæŽ»æ§ã¢ããå«æååç©ã®
枬å®ããã³ã¢ãã³ã®åååå²ã«èããå®éçã§æ
çšãªæ°èŠè©Šè¬ãèšèŒããã FLECãšã¢ããé žãšã®åå¿ã¯ç¬¬ïŒå³ã«ç€ºããã
ãã«é²ãããã®è©Šè¬ã¯ãŸãæ°Žãšåå¿ããå æ°Žå解
çæç©ãšããŠçžåœããã¢ã«ã³ãŒã«ãçæããã ã¯ããã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãš
ãã«ïŒFLECïŒã®åæ ïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšã¿ããŒã«ã®åæïŒ ä¹Ÿç¥ãšãŒãã«100mläžã®ãã«ãªã¬ã³8.3ïœã®æº¶æ¶²
ã«ãBuLiïŒãããµã³äž1.6MïŒ31mlãæ·»å ããã
æ··åç©ã30åéæµããã€ãã§æ°·æµŽã§å·ãããçæ
æ··åç©ã«ã也ç¥ãšãŒãã«40mläžã®ã¢ã»ãã¢ã«ãã
ã2.8mlã®æº¶æ¶²ã15åã§å ããïŒæééæµããã
æ°Ž100mlãå ãããšãŒãã«å±€ãå液濟æã§éãã
也ç¥ïŒMgSO4ïŒããèžçºããããçæç©ããã©
ãã·ãŠã¯ãããã°ã©ãã€ã§ããã«ç²Ÿè£œãããªã°ã
ã€ã³ïŒæ²žç¹80ã110âïŒã§åçµæ¶ããçœè²éç¶æ¶
ãåŸããèç¹101ã103âã質éã¹ãã¯ãã«
M+mïŒe210.151HNMRïŒCDCl3ïŒã0.87ïŒäºéç·ã
3HïŒã1.70ïŒäžéç·ã1HïŒã4.09ïŒäºéç·ã1HïŒã
4.35ã4.65ïŒå€éç·ã1HïŒã7.15ã7.85ïŒå€éç·ã
8HïŒã ïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšã¿ããŒã«ã®å åŠå
å² ç¡æ°Žããªãžã³25mläžã®ïŒâïŒïŒâãã«ãªã¬ãã«ïŒ
ãšã¿ããŒã«4.0ïœã®æº¶æ¶²ã«ãïŒâïŒâã«ã³ãã¢ã³é ž
å¡©åç©ã®çã¢ã«é4.12ïœãæ·»å ããæ··åç©ã宀枩
ã§ïŒæéãããŸããã溶液ãæ°·æ°Žã«ããã
CH2Cl2ã§æœåºãããCH2Cl2ãåžå¡©é žã§æŽã也ç¥
ïŒMgSO4ïŒããèžçºä¹Ÿåºãããç²ãšã¹ãã«ãã¡ã¿
ããŒã«ïŒMeOHïŒ200mlã«æº¶ããâ15âã«å·ããã
æåºçµæ¶ïŒç»åïŒâãåäžæº¶åªããïŒåçµæ¶å
ãã溶解æ§ã®å°ãããžã¢ã¹ãã¬ãªããŒãšã¹ãã«
1.0ïœãçŽç²åœ¢ã§åŸãïŒèç¹159ã160âïŒãïŒã©ã»
ãååç©ã®èç¹152âïŒããã®ãžã¢ã¹ãã¬ãªããŒãš
ã¹ãã«ã®å åŠçŽåºŠã¯ãã©ã«åºå®çžïŒ»ã¢ããããã
ã«ã·ãªã«ã«çµåããïŒâïŒâãžããããã³ãŸã€ã«
ããšãã«ã°ãªã·ã³ãããŒã¯ã«çžïŒœã§æ€æ»ãã99ïŒ
ã§ãã€ãã äžèšãšã¹ãã«ã®å æ°Žå解 也ç¥ãšãŒãã«50mläžã®å åŠçãªçŽç²ãªãžã¢ã¹ã
ã¬ãªããŒãšã¹ãã«1.0ïœã®æº¶æ¶²ã«ãLiAlH40.8ïœã
å ãããæ··åç©ã宀枩ã§ïŒæéãããŸããåŸåŠç
åŸã¢ã«ã³ãŒã«ãåŸããèç¹91ã93âå解ïŒã ã¯ããã®é žïŒïŒïŒâïŒâïŒïŒâãã«ãªã¬ãã«ïŒãš
ãã« ïŒâã«å·ãã也ç¥ãã«ãšã³15mläžã®ãã¹ã²ã³
ïŒ0.8ïœã8.1ïœmolïŒã®æº¶æ¶²ã«ã也ç¥ãã«ãšã³20ml
äžã®å åŠçã«çŽç²ãªã¢ã«ã³ãŒã«ïŒ0.44ïœã2.1ïœ
molïŒãšããªãšãã«ã¢ãã³ïŒ0.30mlã2.1ïœmolïŒ
ã®æº¶æ¶²ã滎äžãããæ·»å å®äºåŸãïŒâã§ïŒæéæ¹
æãç¶ãã次ãã§ããªãšãã«ã¢ãã³å¡©é žå¡©ãæ¿Ÿé
ã§é€ãã濟液ãæžå§ã§æ¿çž®ããæ²¹ãåŸãã α25ïŒïŒ67.9°ïŒCH2Cl2ãïŒïŒïŒ α25/578ïŒïŒ70.5°ïŒCH2Cl2ãïŒïŒïŒ1 HNMRïŒCDCl3ïŒïŒ0.76ïŒäºéç·ã3HïŒã4.30ïŒäº
éç·ã1HïŒã5.47ã5.75ïŒå€éç·ã1HïŒ7.18ã
7.75ïŒå€éç·ã8HïŒ åæC16H13O2Clãšã㊠èšç®å€ïŒïŒ£ã70.46ïŒïŒšã4.80ïŒClã13.00 å®æž¬å€ïŒïŒ£ã70.64ïŒïŒšã4.80ïŒClã13.3 å®éšæ¡ä»¶ 溶å€ãšè©Šè¬ïŒ ã¢ã»ããããªã«ãããã©ããããã©ã³ããã³ã¢
ã»ãã³ã¯ã©ã¹ããŒã³ïŒãŠãªãŒã«ãŒããŒã³ãè±ïŒã
ãè³Œå ¥ãããã¢ããé žæšæºããã³FMOCâClè©Š
è¬ã¯ã·ã°ãïŒã»ã³ãã»ã«ã€ã¹ã»ããºãŒãªå·ãç±³ïŒ
ããåŸãã溶åºç·©è¡æ¶²ã¯ïŒåéã®èžæºæ°Žã«æº¶ãã
ãé ¢é žããã€ããïŒïŒmlïŒïŒãæ°Žé žåãããªãŠ
ã ã§é©åœãªPHã«æ»Žå®ãããFLECâClè©Šè¬ã¯ã¢ã»
ããããªã«ïŒã¢ã»ãã³ïŒïŒïŒïŒïŒã«æº¶ããã15ïœ
molïŒã®æ¿åºŠã§ãã€ããåå¿ç·©è¡æ¶²ã¯ããŠé ž
ïŒ1MïŒããäœããPHãæ°Žé žåãããªãŠã ã§èª¿ç¯ã
ãã èªå°äœåœ¢æïŒ è©ŠæïŒ0.4mlãšç·©è¡æ¶²ïŒ0.1mlãPHïŒãïŒmlã®å
å¿ã¬ã©ã¹ã³ãã§æ··åãããè©Šè¬ïŒ0.5mlïŒãå ãã
åå¿ããããïŒååŸã¬ã©ã¹ç¶ããã³ã¿ã³ã§ã»ãšã
ã©å ãããåå¿æ··åç©ãæœåºãéå°ã®è©Šè¬ãé€
ããæœåºãïŒåããè¿ããšãæ°Žçžã¯æ³šå ¥ã«ãã䜿
ããã åå¿éåºŠïŒ ã¢ããé žãšFLECâClè©Šè¬ãšã®åå¿é床ã第ïŒ
å³ã«ç€ºããããã¯PH8.03ïŒè©Šæãã©ã¹ç·©è¡æ¶²ïŒã§
è©Šè¬ã«ããåžžæ³ã§ã¢ããé žã®èªå°äœåœ¢æïŒäžåºŠã«
äžã€ïŒã«ãã枬å®ãããããæéééåŸãé ¢é žã
æ·»å ããŠåå¿ãæ¢ããã³ã¿ã³æœåºã«ããFLECâ
Clè©Šè¬ã®éå°ãé€ãããæªåå¿ã§æ®ã€ãéã¯ã
âãã¿ã«ã¢ã«ãããïŒã¡ã«ã«ãããšã¿ããŒã«ã§ã«
ã©ã åèªå°äœåœ¢æãã€ãã§æ¶²äœã¯ãããã°ã©ãã€
ãŒã«ãã枬å®ãããçµæããåäžæ¹æ³ã ãFLEC
âClè©Šè¬ãªãã«ïŒã¢ããé žã®æåã®éïŒåŠçãã
溶液ãšæ¯èŒããããããFLECâèªå°äœãžã®è»¢å
çãèšç®ããããåç¹ã¯ïŒåã®æž¬å®ã®å¹³åã§ã
ãã ã¢ã¹ãã©ã®ã³é žããã³ã°ã«ã¿ãã³é žã®åå¿é床
ã«å¯ŸããPHã®åœ±é¿ã第ïŒå³ã«ç€ºããïŒåã®åå¿æ
éã§äžèšãšåäžæ¹æ³ã§å®æœãããPH8.01ã8.46ã
9.01ã9.47ããã³10.23ã§æž¬å®ãããPHã¯ç·©è¡æ¶²æ·»
å åŸã®åå¿æº¶æ¶²ã§æž¬å®ããã FLECâClãã³FMOCâClè©Šè¬ãšããªã³ãã°ã¿
ã¿ãã³é žããããªã³ããªãžã³ãšã®çžå¯Ÿåå¿é床
ã¯ãæšæºã¢ããé žæº¶æ¶²ãè©Šè¬ã®åã ã§èªå°äœã«å€
ãããšãåŸãããåçãšãæ··åFLECïŒFMOCè©Š
è¬ã䜿ã€ããšãã®çµæãšãæ¯èŒããããšã«ãã決
å®ãããèªå°äœãã¯ãããã°ã©ãã€ãŒã§åé¢ãã
ããŒã¯é¢ç©ãæ¯èŒããã 第ïŒå³ã«ãéçžæ¶²äœã¯ãããã°ã©ãã€ãŒã§ä»¶ãª
ã€ãè¢å æšæºãžã¢ã¹ãã¬ãªããŒã«ã«ããã³é žå¡©ãš
ããŠã®17çš®ã®ã¢ãã³é žã®åå²ã瀺ãã å®éšæ¡ä»¶ïŒ FLECâClè©Šè¬ãã¢ã»ããããªã«ïŒã¢ã»ãã³
ïŒ1/4ïŒã15ïœïŒã«æº¶ãããåå¿ç·©è¡æ¶²ã¯ããŠé žå¡©
ç·©è¡æ¶²ã1MãPH6.5ã§ããã è©Šæ0.4mlãšããŠé žå¡©ç·©è¡æ¶²0.1mlãæ··åããã
ãã®æº¶æ¶²ã«è©Šæ0.5mlãå ãããïŒåã®åå¿æé
åŸãæ··åç©ããã³ã¿ã³ã§ïŒåæœåºããããã³ã¿ã³
æœåºç©ãæšãŠãæ°Žçžã¯æ³šå ¥ã«ãã䜿ãããé žåºã
ãããªãæ¯èŒççæ°Žæ§ã¢ãã³ã®èªå°äœåœ¢æã®ãšã
ã¯ãæœåºå·¥çšãã¯ã¶ãã芪氎æ§ã¢ãã³ãå žåçã«
ã¯ããããã·ãããªã³ãŸãã¯ããã©ãžã³ãšã®åå¿
ã«ããéå°ã®è©Šè¬ãé€å»ããã
ãè¡šã
åé¢æ¡ä»¶ïŒã¢ããé
žïŒïŒ
ã«ã©ã ïŒã¹ããšãªãœã«ããªã¯ãã«å€ïŒïœïŒ3ÎŒ
ïœïŒãå ãŠããã150Ã4.6mmã溶åºç·©è¡æ¶²ïŒé ¢é ž
ïŒãããã«ïŒpromilleïŒãPH4.35ãæµéïŒ0.3mlïŒ
åã äžèšç¬¬ïŒè¡šã«ã幟ã€ãã®ã¢ããå«æè¬å€ã®
Kâ²âå€ãåå²ä¿æ°Î±å€ã瀺ãã
ïœïŒãå ãŠããã150Ã4.6mmã溶åºç·©è¡æ¶²ïŒé ¢é ž
ïŒãããã«ïŒpromilleïŒãPH4.35ãæµéïŒ0.3mlïŒ
åã äžèšç¬¬ïŒè¡šã«ã幟ã€ãã®ã¢ããå«æè¬å€ã®
Kâ²âå€ãåå²ä¿æ°Î±å€ã瀺ãã
ãè¡šã
第ïŒå³ã«ãã©ã»ãFLECâClè©Šè¬ã§èªå°äœåœ¢æ
ããã¡ãããããŒã«ãå¿èéžæçβâã¢ãã¬ããª
ã³å容äœé®æè¬ïŒÎ²é®æè¬ïŒã®ã©ã»ã溶液ã®åå²
ã瀺ãã ã«ã©ã ïŒ5ÎŒïœã®ãªã¯ãã«å€ïŒã¹ããšãªãœã«ãïŒ
ãå å¡«ãã4.6Ã250mmã溶é¢å€ïŒã¢ã»ããããªã«
60ïŒ ãæ°Ž40ïŒ ã ã¢ããé žæšæºã®å åŠçŽåºŠãè©Šè¬ã®å åŠçŽåºŠãã
ãã³èªå°äœåœ¢æã®ã©ã»ãåã®è€åå¹æã決å®ãã
ããã«ãåžè²©ã®ãå åŠçã«çŽç²ãªãâã°ã«ã¿ã
ã³ã®èªå°äœåœ¢æãšåå²ã第ïŒå³ã«ç€ºããFLECâ
Clã§èªå°äœåœ¢æããâã°ã«ã¿ãã³ïŒïŒïœmolïŒ
ïŒãå°éã®ïŒ€âã°ã«ã¿ãã³ïŒ2ÎŒmolïŒïŒã®æš
æºæ·»å ã«ãã枬å®ããâã°ã«ã¿ãã³ããŒã¯ã¯ïŒ¬
âã°ã«ã¿ãã³ã®0.6ãããã«ã«ãããã äžèšç¬¬ïŒè¡šã«ãéçžã«ã©ã ã§åé¢ãããµã€ãã®
ããããã¢ããé žã®Kâ²ããã³åå²ä¿æ°Î±å€ã瀺
ãã
ããã¡ãããããŒã«ãå¿èéžæçβâã¢ãã¬ããª
ã³å容äœé®æè¬ïŒÎ²é®æè¬ïŒã®ã©ã»ã溶液ã®åå²
ã瀺ãã ã«ã©ã ïŒ5ÎŒïœã®ãªã¯ãã«å€ïŒã¹ããšãªãœã«ãïŒ
ãå å¡«ãã4.6Ã250mmã溶é¢å€ïŒã¢ã»ããããªã«
60ïŒ ãæ°Ž40ïŒ ã ã¢ããé žæšæºã®å åŠçŽåºŠãè©Šè¬ã®å åŠçŽåºŠãã
ãã³èªå°äœåœ¢æã®ã©ã»ãåã®è€åå¹æã決å®ãã
ããã«ãåžè²©ã®ãå åŠçã«çŽç²ãªãâã°ã«ã¿ã
ã³ã®èªå°äœåœ¢æãšåå²ã第ïŒå³ã«ç€ºããFLECâ
Clã§èªå°äœåœ¢æããâã°ã«ã¿ãã³ïŒïŒïœmolïŒ
ïŒãå°éã®ïŒ€âã°ã«ã¿ãã³ïŒ2ÎŒmolïŒïŒã®æš
æºæ·»å ã«ãã枬å®ããâã°ã«ã¿ãã³ããŒã¯ã¯ïŒ¬
âã°ã«ã¿ãã³ã®0.6ãããã«ã«ãããã äžèšç¬¬ïŒè¡šã«ãéçžã«ã©ã ã§åé¢ãããµã€ãã®
ããããã¢ããé žã®Kâ²ããã³åå²ä¿æ°Î±å€ã瀺
ãã
ãè¡šã
ãè¡šã
äžèšã®ããã«ãéå°ã®è©Šè¬ãçš®ã
ã®æ¹æ³ã«ãã
é€å»ã§ãããã¢ãã³ã®åé¢ã®ãšã䜿ãã®ã奜ãŸã
ãïŒæ¹æ³ã¯ã枬å®ããããšããååç©ãšåé¢äžç·©
è¡ããªãçæç©ãçããã¢ãã³ãšéå°ã®è©Šè¬ãšã
åå¿ãããããšã§ãããã¢ãã³ããã³èªå°äœã¯æ°Ž
溶æ§ã§ããã¹ãã§ããããã®ãããªã¢ãã³ã®äŸã¯
ããããã·ãããªã³ããã³ããã©ãžã³ã§ããã 芪氎æ§ã¢ããèªå°äœã圢æããã¢ããé žãŸãã¯
ã¢ããç³ãåé¢ãããšã䜿ãã®ã奜ãŸããå¥ã®æ¹
æ³ã¯ãäœæ¥µæ§ã®æº¶å€ãããšãã°ãã³ã¿ã³ãŸãã¯ã
ããµã³ã§éå°ã®è©Šè¬ãæœåºããããšã§ããã æ¬çºæã«ããè©Šè¬ã¯ã¢ããå«æã©ã»ãæ··åç©ã®
åååå²ã«ãå¿çšã§ãããHPLCã«ããèªå°äœã
åé¢åŸãåžžæ³ããšãã°é žãŸãã¯å¡©åºæ§å æ°Žå解ãŸ
ãã¯æ°ŽçŽ åå解ã«ããã¢ããå«æååç©ãåçã
ãã äžèšç¬¬ïŒè¡šã«ãçŸåšã®ã«ã©ã åèªå°äœåœ¢æå€ãš
FLECâClã®æ¯èŒãããFLECâ詊è¬ã®åªããŠ
ããããšãäŸç€ºããã
é€å»ã§ãããã¢ãã³ã®åé¢ã®ãšã䜿ãã®ã奜ãŸã
ãïŒæ¹æ³ã¯ã枬å®ããããšããååç©ãšåé¢äžç·©
è¡ããªãçæç©ãçããã¢ãã³ãšéå°ã®è©Šè¬ãšã
åå¿ãããããšã§ãããã¢ãã³ããã³èªå°äœã¯æ°Ž
溶æ§ã§ããã¹ãã§ããããã®ãããªã¢ãã³ã®äŸã¯
ããããã·ãããªã³ããã³ããã©ãžã³ã§ããã 芪氎æ§ã¢ããèªå°äœã圢æããã¢ããé žãŸãã¯
ã¢ããç³ãåé¢ãããšã䜿ãã®ã奜ãŸããå¥ã®æ¹
æ³ã¯ãäœæ¥µæ§ã®æº¶å€ãããšãã°ãã³ã¿ã³ãŸãã¯ã
ããµã³ã§éå°ã®è©Šè¬ãæœåºããããšã§ããã æ¬çºæã«ããè©Šè¬ã¯ã¢ããå«æã©ã»ãæ··åç©ã®
åååå²ã«ãå¿çšã§ãããHPLCã«ããèªå°äœã
åé¢åŸãåžžæ³ããšãã°é žãŸãã¯å¡©åºæ§å æ°Žå解ãŸ
ãã¯æ°ŽçŽ åå解ã«ããã¢ããå«æååç©ãåçã
ãã äžèšç¬¬ïŒè¡šã«ãçŸåšã®ã«ã©ã åèªå°äœåœ¢æå€ãš
FLECâClã®æ¯èŒãããFLECâ詊è¬ã®åªããŠ
ããããšãäŸç€ºããã
ãè¡šã
ã¯ããã®é
žïŒâïŒïŒâãã«ãªã¬ãã«ïŒãšãã«ã
äŸãšããŠèšèŒããå¯äžã®è©Šè¬ã§ããããåæ§ã«äœ¿
çšã§ããå€æ°ã®æ§é é¡äŒŒäœããããè«æ±ã®ç¯å²ç¬¬
ïŒé ã®äžè¬åŒã®ïŒ²ãšããŠã®ã¡ãã«ãããªãã«ãªã
ã¡ãã«ãŸãã¯äžå±€é«çŽã®ã¢ã«ãã«åºã§çœ®ã代ãã
ããšãã§ãããå¡©çŽ ïŒžã®ä»£ãã«ãFMOCâè©Šè¬
ã§è©Šéšããè¯å¥œãªè±é¢åºã§ããããšãããã€ãè
çŽ ãã¢ãžãåºããŸãã¯ã¹ã¯ã·ã³ã€ããžã«åºãçšã
ãããšãå¯èœã§ãã€ãã
äŸãšããŠèšèŒããå¯äžã®è©Šè¬ã§ããããåæ§ã«äœ¿
çšã§ããå€æ°ã®æ§é é¡äŒŒäœããããè«æ±ã®ç¯å²ç¬¬
ïŒé ã®äžè¬åŒã®ïŒ²ãšããŠã®ã¡ãã«ãããªãã«ãªã
ã¡ãã«ãŸãã¯äžå±€é«çŽã®ã¢ã«ãã«åºã§çœ®ã代ãã
ããšãã§ãããå¡©çŽ ïŒžã®ä»£ãã«ãFMOCâè©Šè¬
ã§è©Šéšããè¯å¥œãªè±é¢åºã§ããããšãããã€ãè
çŽ ãã¢ãžãåºããŸãã¯ã¹ã¯ã·ã³ã€ããžã«åºãçšã
ãããšãå¯èœã§ãã€ãã
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86371286A | 1986-05-16 | 1986-05-16 | |
US863712 | 1986-05-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS63501507A JPS63501507A (ja) | 1988-06-09 |
JPH0552821B2 true JPH0552821B2 (ja) | 1993-08-06 |
Family
ID=25341625
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP62503117A Granted JPS63501507A (ja) | 1986-05-16 | 1987-05-18 | å åŠæŽ»æ§è©Šè¬ããã³å¯Ÿæäœã¢ãã³ååç©ã®æž¬å®æ³ |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0270595B1 (ja) |
JP (1) | JPS63501507A (ja) |
AT (1) | ATE55594T1 (ja) |
DE (1) | DE3764347D1 (ja) |
DK (1) | DK174265B1 (ja) |
FI (1) | FI90410C (ja) |
NO (1) | NO166584C (ja) |
WO (1) | WO1987006929A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE467738B (sv) * | 1988-08-18 | 1992-09-07 | Eka Nobel Ab | Nya 9-antrylalkylfoereningar, foerfarande foer framstaellning daerav samt anvaendning daerav |
WO2009158668A1 (en) * | 2008-06-26 | 2009-12-30 | Prolynx Llc | Prodrugs and drug-macromolecule conjugates having controlled drug release rates |
KR20170029965A (ko) * | 2015-09-08 | 2017-03-16 | 죌ìíì¬ ìë¯žë žë¡ì§ì€ | D-ì륎Ʞëì ì ì¡° ë°©ë² |
CN113655131B (zh) * | 2021-04-23 | 2023-09-29 | åå°å€èœçç©å¶è¯(倧è¿åž)æéå ¬åž | äžç§Fmoc-Ile-OHçæå ³ç©èŽšæ£æµæ¹æ³ |
CN115541730A (zh) * | 2022-06-29 | 2022-12-30 | å京éå¿çç©å»è¯æéå ¬åž | äžç§ä¿æ€æ°šåºé žå¯¹æ åŒæäœçæµå®æ¹æ³ |
-
1987
- 1987-05-18 DE DE8787903467T patent/DE3764347D1/de not_active Expired - Lifetime
- 1987-05-18 WO PCT/SE1987/000245 patent/WO1987006929A1/en active IP Right Grant
- 1987-05-18 JP JP62503117A patent/JPS63501507A/ja active Granted
- 1987-05-18 AT AT87903467T patent/ATE55594T1/de not_active IP Right Cessation
- 1987-05-18 EP EP87903467A patent/EP0270595B1/en not_active Expired - Lifetime
-
1988
- 1988-01-13 FI FI880145A patent/FI90410C/fi not_active IP Right Cessation
- 1988-01-15 DK DK198800175A patent/DK174265B1/da active IP Right Grant
- 1988-01-18 NO NO880191A patent/NO166584C/no unknown
Also Published As
Publication number | Publication date |
---|---|
EP0270595A1 (en) | 1988-06-15 |
FI90410C (fi) | 1994-02-10 |
DE3764347D1 (de) | 1990-09-20 |
FI90410B (fi) | 1993-10-29 |
DK174265B1 (da) | 2002-10-28 |
WO1987006929A1 (en) | 1987-11-19 |
NO166584C (no) | 1991-08-14 |
DK17588A (da) | 1988-01-15 |
DK17588D0 (da) | 1988-01-15 |
FI880145A (fi) | 1988-01-13 |
EP0270595B1 (en) | 1990-08-16 |
ATE55594T1 (de) | 1990-09-15 |
NO880191D0 (no) | 1988-01-18 |
NO166584B (no) | 1991-05-06 |
FI880145A0 (fi) | 1988-01-13 |
NO880191L (no) | 1988-01-18 |
JPS63501507A (ja) | 1988-06-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5360819A (en) | Molecular analytical release tags and their use in chemical analysis | |
US5296599A (en) | Activated carbamates compounds | |
JPS59150341A (ja) | ã¿ã³ãã¯è³ªé ååææ³ããã³è©Šè¬ | |
BÃŒschges et al. | Chloroformates and isothiocyanates derived from 2-arylpropionic acids as chiral reagents: synthetic routes and chromatographic behaviour of the derivatives | |
JPH0552821B2 (ja) | ||
US4818704A (en) | Method for the separation and determination of enantiomeric amine compounds using an optically active agent | |
US5807748A (en) | N-terminal protein sequencing reagents and methods which form amino acid detectable by a variety of techniques | |
JPH11255773A (ja) | âãã©ããããã§ãã«ã¢ã©ãã³ã®è£œé æ¹æ³ | |
Zhao et al. | Degradingdehydroabietylisothiocyanate as a chiral derivatizing reagent for enantiomeric separations by capillary electrophoresis | |
Solladie-Cavallo et al. | Synthesis of (2S, 3R)-3-amino-2-hydroxy-5-methylhexanoic acid: bridging effect of potassium fluoride | |
WO2006070737A1 (ja) | ãã³ãŒã³ç°äžã«äºçœ®æåºãæããβïŒãã³ãžã«ãªãã·ã¢ã¹ãã©ã®ã³é žèªå°äœ | |
BÃŒschges et al. | 4-(6-Methoxy-2-naphthyl)-2-butyl chloroformate enantiomers: New reagents for the enantiospecific analysis of amino compounds in biogenic matrices | |
Arora et al. | Preparation and biological evaluation of a potential photoaffinity label for the prostaglandin H2/thromboxane A2 receptor | |
WO1996037465A1 (en) | Chiral isothiocyanates and their use as chiral derivatising agents | |
JP4265324B2 (ja) | æ°èŠãªãã³ãã³é žèªå°äœåã³ãã®åææ¹æ³ | |
JP3121072B2 (ja) | ã³ã³ã¢ã«ããã³ãçµåããå åŠç°æ§äœåé¢å€ | |
JPH07209303A (ja) | çºèå æšèçšè©Šè¬ | |
US5015755A (en) | 9-anthrylalkyl compounds | |
Andrisano et al. | Stereoselectivity at αâadrenoreceptor subtypes: observations with the enantiomers of WB 4101 separated through their amides of NâTosylâ(S)âproline | |
JPS6234035B2 (ja) | ||
JPS63221809A (ja) | é«é液äœã¯ãããã°ã©ãã€âçšèªå°äœåè©Šè¬ | |
FR2598422A1 (fr) | Pseudo-peptide comportant au moins la sequence de l'acide g-glutamyl-aspartique ou l'un de ses derives, son utilisation dans la preparation d'une composition pharmaceutique et composition pharmaceutique en resultant | |
JPS60155967A (ja) | ã¬ã¹ã¯ãããã°ã©ãåºå®çžåã³ãããçšããé¡åäœæ··åç©ã®åææ³ | |
JPH0819122B2 (ja) | ïŒâïŒïŒâã€ãœããªã·ã¢ãããããªãžã³âïŒâã€ã«ïŒâïŒïŒïŒïŒïŒâãã³ãŸãªããµãžã¢ãŸãŒã«ã®æ°èŠå åŠæŽ»æ§èªå°äœããã³ã¢ãã³åæçšèå æšèè©Šè¬ | |
EP0166650A1 (fr) | Procédé d'ouverture du cycle des gem dicyanoépoxydes et nouveaux composés obtenus par ce procédé |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |