JPH0135823B2 - - Google Patents
Info
- Publication number
- JPH0135823B2 JPH0135823B2 JP55152151A JP15215180A JPH0135823B2 JP H0135823 B2 JPH0135823 B2 JP H0135823B2 JP 55152151 A JP55152151 A JP 55152151A JP 15215180 A JP15215180 A JP 15215180A JP H0135823 B2 JPH0135823 B2 JP H0135823B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- reaction
- amino acid
- compound
- 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
Links
- 238000000034 method Methods 0.000 claims abstract description 25
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 24
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims abstract description 20
- -1 β-amino acid compound Chemical class 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 239000007858 starting material Substances 0.000 abstract description 12
- 239000003242 anti bacterial agent Substances 0.000 abstract description 6
- 229940088710 antibiotic agent Drugs 0.000 abstract description 6
- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 abstract description 5
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 abstract description 5
- 150000003952 β-lactams Chemical group 0.000 abstract description 4
- 229930189801 nocardicin Natural products 0.000 abstract description 3
- 150000001576 beta-amino acids Chemical class 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 4
- 125000003460 beta-lactamyl group Chemical group 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- BBJIPMIXTXKYLZ-UHFFFAOYSA-N isoglutamic acid Chemical compound OC(=O)CC(N)CC(O)=O BBJIPMIXTXKYLZ-UHFFFAOYSA-N 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000002132 β-lactam antibiotic Substances 0.000 description 4
- 229940124586 β-lactam antibiotics Drugs 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940000635 beta-alanine Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- RBOKYBCBRQCEHG-NSHDSACASA-N (3s)-5-methoxy-5-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound COC(=O)C[C@H](CC(O)=O)NC(=O)OCC1=CC=CC=C1 RBOKYBCBRQCEHG-NSHDSACASA-N 0.000 description 2
- UJOYFRCOTPUKAK-UHFFFAOYSA-N 3-ammonio-3-phenylpropanoate Chemical compound [O-]C(=O)CC([NH3+])C1=CC=CC=C1 UJOYFRCOTPUKAK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
- PXJFLUYRGQUUIN-UHFFFAOYSA-N dimethyl 3-aminopentanedioate Chemical compound COC(=O)CC(N)CC(=O)OC PXJFLUYRGQUUIN-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- CTLHFZBIZFOLIK-SCSAIBSYSA-N (3r)-3-amino-5-methoxy-5-oxopentanoic acid Chemical compound COC(=O)C[C@H](N)CC(O)=O CTLHFZBIZFOLIK-SCSAIBSYSA-N 0.000 description 1
- CTLHFZBIZFOLIK-BYPYZUCNSA-N (3s)-3-amino-5-methoxy-5-oxopentanoic acid Chemical compound COC(=O)C[C@@H](N)CC(O)=O CTLHFZBIZFOLIK-BYPYZUCNSA-N 0.000 description 1
- SEWIYICDCVPBEW-SCSAIBSYSA-N (4r)-4-amino-5-methoxy-5-oxopentanoic acid Chemical compound COC(=O)[C@H](N)CCC(O)=O SEWIYICDCVPBEW-SCSAIBSYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- HZMSRODLTUNQSM-UHFFFAOYSA-N 2,3-diamino-5-hydroxypentanoic acid Chemical compound OCCC(N)C(N)C(O)=O HZMSRODLTUNQSM-UHFFFAOYSA-N 0.000 description 1
- WFRNRWHEMQWFRH-UHFFFAOYSA-N 2-(aminomethyl)-3-hydroxybutanoic acid Chemical compound CC(O)C(CN)C(O)=O WFRNRWHEMQWFRH-UHFFFAOYSA-N 0.000 description 1
- HBICVCPHTYGKKD-UHFFFAOYSA-N 2-(azaniumylmethyl)butanoate Chemical compound CCC(CN)C(O)=O HBICVCPHTYGKKD-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- QRDUQWYMGXZIKM-UHFFFAOYSA-N 3-(benzylamino)propanoic acid Chemical compound OC(=O)CCNCC1=CC=CC=C1 QRDUQWYMGXZIKM-UHFFFAOYSA-N 0.000 description 1
- HFTVKHFILHLXJF-NSCUHMNNSA-N 3-[(e)-2-aminoethenyl]sulfanyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(S\C=C\N)=C(C(O)=O)N2C(=O)C(C(O)C)C21 HFTVKHFILHLXJF-NSCUHMNNSA-N 0.000 description 1
- NVUIQQXPQNPDCU-UHFFFAOYSA-N 3-amino-2-methoxypropanoic acid Chemical compound COC(CN)C(O)=O NVUIQQXPQNPDCU-UHFFFAOYSA-N 0.000 description 1
- AHBISXSASJMHLS-UHFFFAOYSA-N 3-amino-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)CC(N)CC(O)=O AHBISXSASJMHLS-UHFFFAOYSA-N 0.000 description 1
- HWUHAKIXIFBAGW-UHFFFAOYSA-N 3-amino-5-hydroxypentanoic acid Chemical compound OCCC(N)CC(O)=O HWUHAKIXIFBAGW-UHFFFAOYSA-N 0.000 description 1
- CTLHFZBIZFOLIK-UHFFFAOYSA-N 3-amino-5-methoxy-5-oxopentanoic acid Chemical compound COC(=O)CC(N)CC(O)=O CTLHFZBIZFOLIK-UHFFFAOYSA-N 0.000 description 1
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 1
- UHBAPGWWRFVTFS-UHFFFAOYSA-N 4,4'-dipyridyl disulfide Chemical compound C=1C=NC=CC=1SSC1=CC=NC=C1 UHBAPGWWRFVTFS-UHFFFAOYSA-N 0.000 description 1
- MWKMQPSNTJCASD-UHFFFAOYSA-N 4-phenylazetidin-2-one Chemical compound N1C(=O)CC1C1=CC=CC=C1 MWKMQPSNTJCASD-UHFFFAOYSA-N 0.000 description 1
- HRSMZGWLXJYRSR-UHFFFAOYSA-N 5-acetyloxy-3-aminopentanoic acid Chemical compound CC(=O)OCCC(N)CC(O)=O HRSMZGWLXJYRSR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- SEWIYICDCVPBEW-BYPYZUCNSA-N L-glutamate methyl ester Chemical compound COC(=O)[C@@H](N)CCC(O)=O SEWIYICDCVPBEW-BYPYZUCNSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000005236 alkanoylamino group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- GDPOAFNYCGJPME-UHFFFAOYSA-N dimethyl 2-(phenylmethoxycarbonylamino)pentanedioate Chemical compound COC(=O)CCC(C(=O)OC)NC(=O)OCC1=CC=CC=C1 GDPOAFNYCGJPME-UHFFFAOYSA-N 0.000 description 1
- GCARTCPMCGRKDU-UHFFFAOYSA-N dimethyl 3-(phenylmethoxycarbonylamino)pentanedioate Chemical compound COC(=O)CC(CC(=O)OC)NC(=O)OCC1=CC=CC=C1 GCARTCPMCGRKDU-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- RXHXPUPRSNKIGG-SCSAIBSYSA-N methyl 2-[(2r)-4-oxoazetidin-2-yl]acetate Chemical compound COC(=O)C[C@H]1CC(=O)N1 RXHXPUPRSNKIGG-SCSAIBSYSA-N 0.000 description 1
- RXHXPUPRSNKIGG-BYPYZUCNSA-N methyl 2-[(2s)-4-oxoazetidin-2-yl]acetate Chemical compound COC(=O)C[C@@H]1CC(=O)N1 RXHXPUPRSNKIGG-BYPYZUCNSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
æ¬çºæã¯ïŒâã¢ãŒããžãã³èªå°äœã®æ°èŠãªåæ
æ³ã«é¢ããã ïŒâã¢ãŒããžãã³èªå°äœã¯ãæèæ§ç©è³ªãšããŠ
çŸåšæã泚ç®ãããŠããβâã©ã¯ã¿ã ç³»æçç©è³ª
ã®åºæ¬éªšæ Œããªãååç©ã§ãããäŸãã°ãæçç©
質ãšããŠçŸåšäžå¿çäœçœ®ãå ããŠããããã·ãªã³
ç³»æçç©è³ªãã»ãã¢ãã¹ããªã³ç³»æçç©è³ªã䞊ã³
ã«æ¬¡ã®äžä»£ãã«ãªãæçç©è³ªãšããããŠããããš
ããã€ã·ã³ããã«ã«ãžã·ã³çã¯ããããäžèšåŒ ã§ç€ºãããïŒâã¢ãŒããžãã³éªšæ Œãå«ãã§ããã
ãšã¯ããç¥ãããŠãããšããã§ããã ãã®ãããªïŒâã¢ãŒããžãã³éªšæ Œãå«ãåå
ç©ãããªãã¡ãïŒâã¢ãŒããžãã³èªå°äœãåæã
ãããã®æ¹æ³ã¯åŸæ¥ããããã€ãææ¡ãããŠã
ããäŸãã°ãβâã¢ã©ãã³ã®ãšã¹ãã«ããã°ãªã
ã€ãŒåå¿ã«ããïŒâã¢ãŒããžãã³ãåŸãæ¹æ³ãJ.
Am.Chem.Soc.ã71ã2124ïŒ1949ïŒïŒChem.ïŒ
Ind.ã1964ã2097çåç §ããâ眮æβâã¢ã©ã
ã³ãå¡©åããªãã«â第äžçŽã¢ãã³ã«ããçž®åãã
ãŠïŒâã¢ãŒããžãã³ãåŸãæ¹æ³ãJ.Org.Chem.ã
23ã1102ïŒ1958ïŒçåç §ããβâã¢ããé žèªå°äœã
ãžã·ã¯ãããã·ã«ã«ã«ããžã€ããã§åŠçããŠïŒâ
ã¢ãŒããžãã³èªå°äœãåŸãæ¹æ³ãTetrahedron
Lettersã21ã2783ïŒ1980ïŒïŒJ.Am.Chem.Soc.ã
102ã2060ïŒ1980ïŒçåç §ããªã©ãå ±åãããŠã
ãããããããããåŸæ¥ææ¡ãããŠããæ¹æ³ã¯ã
ãã°ãã°åºè³ªã®æ§é ã«å·Šå³ãããããé«äŸ¡ãªè©Šè¬
ãçšããå¿ èŠããã€ãããåçãäžååã§ãã€ã
ãããçã®äžå©ããããå°åºå·¥æ¥çã«æå¹ãªæ¹æ³
ã§ãããšã¯èšãé£ãã ããããªãããβâã©ã¯ã¿ã ç°ãæããç©è³ªã
å·¥æ¥çã«å®äŸ¡ãªåºçºåæåã³è©Šè¬ãã容æã«è£œé
ããããšãå¯èœãšãªãã°ãçŸåšæ³šç®ãããŠããã
ãšããã€ã·ã³ããã«ã«ãžã·ã³ããªãªãããã¯ã¢ã·
ããçã®Î²âã©ã¯ã¿ã ç³»æçç©è³ªã®å šåæãå¯èœ
ãšãªãããã®å·¥æ¥ç䟡å€ã¯çµ¶å€§ãªãã®ãšãªãããš
ã¯æçœã§ããã ããã§ãæ¬çºæè ãã¯Î²âã¢ããé žååç©ãåº
çºåæãšãããããβâã©ã¯ã¿ã ååç©ãããªã
ã¡ïŒâã¢ãŒããžãã³èªå°äœã«å€ããæ¹æ³ã«ã€ãé
æç 究ãè¡ãªã€ãçµæãã¢ã«ãã«ãããªã«ã®ååš
äžã«çž®åéç°è©Šè¬ãšããŠããªããšãã«ãã¹ãã€ã³
åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ãããªããããã
ãé žåéå è©Šè¬ã䜿çšããã°ãβâã¢ããé žåå
ç©ã極ããŠç°¡åã«å¥œåçã§å¯Ÿå¿ããïŒâã¢ãŒããž
ãã³èªå°äœã«å€ãããããšãèŠãåºããæ¬çºæã
å®æããã«è³ã€ãã ããããŠãæ¬çºæã«åŸãã°ãã¢ããåºãã¢ã眮
æãããŠããŠãããβâã¢ããé žååç©ãã¢ã«ã
ã«ãããªã«ã®ååšäžã«ããªããšãã«ãã¹ãã€ã³å
ã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ã§åŠçããããšãç¹
城ãšããïŒâã¢ãŒããžãã³èªå°äœã®è£œé æ¹æ³ãæ
äŸãããã æ¬çºæã®æ¹æ³ã¯ãã¢ããåºãã¢ã眮æãããŠã
ãŠãããβâã¢ããé žååç©ã«å¯ŸããŠåºãé©çšã
ãããšãã§ããå©ç¹ããããïŒâã¢ãŒããžãã³èª
å°äœã®äžè¬çåææ³ãæäŸãããã®ã§ããã ããããŠãæ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãšã
ãŠäœ¿çšãããã¢ããåºãã¢ã眮æãããŠããŠãã
ãβâã¢ããé žååç©ã¯ãå ·äœçã«ã¯ãäžèšäžè¬
åŒ åŒäžãR1åã³R2ã¯ããããç¬ç«ã«æ°ŽçŽ ååã
ã¢ããåºã眮æã¢ããåºãã¢ã«ã³ãã·åºåã¯åå¿
ã«é¢äžããªã眮æåºãæããŠããŠãããäžäŸ¡ã®ç
åæ°ŽçŽ åºãè¡šãããR3åã³R4ã¯ããããç¬ç«ã«
æ°ŽçŽ åååã¯åå¿ã«é¢äžããªã眮æåºãæããŠã
ãŠãããäžäŸ¡ã®çåæ°ŽçŽ åºãè¡šãããR5ã¯æ°ŽçŽ
åååã¯äžäŸ¡ã®çåæ°ŽçŽ åºãè¡šãããæãã¯R4
ãšR5ãšã¯äžç·ã«ãªã€ãŠÎ²âã©ã¯ã¿ã ç³»æçç©è³ª
ããβâã©ã¯ã¿ã ç°ãé€ããåŸã«æ®ãç°å¡ãè¡šã
ããŠãããã ã§ç€ºãããååç©ãå å«ããã äžèšåŒïŒïŒã«ãããŠãR1åã³ïŒåã¯R2ã«ã
ã€ãŠè¡šããããã眮æã¢ããåºããšããŠã¯ãäŸã
ã°ããã³ãžã«ã¢ãããããªããšãã«ã¡ãã«ã¢ãã
åºçã®ã¢ã©ã«ãã«ã¢ããåºïŒãã³ãžã«ãªãã·ã«ã«
ããã«ã¢ãããtertâãããã·ã«ã«ããã«ã¢ãã
åºçã®ã¢ã©ã«ãã«ïŒåã¯ã¢ã«ãã«ïŒãªãã·ã«ã«ã
ãã«ã¢ããåºïŒã¢ã»ãã«ã¢ããåºçã®ã¢ã«ã«ãã€
ã«ã¢ããåºïŒããšãã«ã¢ã»ãã«ã¢ãããããšãã
ã·ã¢ã»ãã«ã¢ãããαâããããã·ããšãã«ã¢ã»
ãã«ã¢ãããαâã¹ã«ãããšãã«ã¢ã»ãã«ã¢ãã
åºçã®ã¢ã©ã«ã«ãã€ã«ã¢ããåºïŒïŒâããšãã«ã¢
ã»ãã«ã¢ãããïŒâïŒ1HïŒâããã©ãŸãªã«ã¢ã»
ãã«ã¢ãããïŒïŒâããªãžã«ããªïŒã¢ã»ãã«ã¢ã
ããïŒïŒâã¢ããâïŒâãã¢ãŸãªã«ïŒã¢ã»ãã«ã¢
ããåºçãžã®ãããã¢ã©ã«ã«ãã€ã«ã¢ããåºïŒã·
ã¢ãã¢ã»ãã«ã¢ããåºãαâã¡ããã·ã€ããâïŒ
âããªã«ã¢ã»ãã«ã¢ããåºçãæãããããŸãã
ãã¢ã«ã³ãã·åºããšããŠã¯ãäŸãã°ãã¡ããã·ã
ãšããã·ãïœâãããã¯isoâããããã·ãïœâã
isoâãsecâãããã¯tertâãããã·åºçã®äœçŽ
ã¢ã«ã³ãã·åºã奜é©ã§ããã R1ãR5ã«ãã€ãŠè¡šãããããäžäŸ¡ã®çåæ°ŽçŽ
åºãã¯éç¶ãç°ç¶ïŒè³éŠç°ç¶åã¯èç°åŒã®ããã
ãã§ãã€ãŠãããïŒåã³ãããã®çµåããã®ãã
ããã§ãã€ãŠããããäžè¬ã«10å以äžã®ççŽ åå
ãå«æãããã®ã奜é©ã§ãããç¹ã«ã¯é£œåããŠã
ããã®ãæãŸããããããäžäŸ¡ã®çåæ°ŽçŽ åºã®å ·
äœäŸãšããŠã¯ãå ·äœçã«ã¯ãã¢ã«ãã«åºãäŸãã°
ã¡ãã«ããšãã«ãïœâãããã¯isoâãããã«ã
ïœâãisoâãsecâãããã¯tertâããã«åºçã®
äœçŽã¢ã«ãã«åºïŒã¢ãªã«åºçã®ã¢ã«ã±ãã«åºïŒãš
ããã«åºçã®ã¢ã«ããã«åºïŒã·ã¯ãããã·ã«ãã·
ã¯ããããã«åºçã®ã·ã¯ãã¢ã«ãã«åºïŒããšã
ã«ããããã«åºçã®ã¢ãªãŒã«åºïŒãã³ãžã«ãããš
ããã«ãããšãã«ãããã«åºçã®ã¢ã©ã«ãã«åºç
ãæããããã ãŸãããããäžäŸ¡ã®çåæ°ŽçŽ åºäžã«ååšããã
ãåå¿ã«é¢äžããªã眮æåºããšããŠã¯ãäŸãã°ã
æ°Žé žåºãäœçŽã¢ã«ã³ãã·ã«ã«ããã«åºãã¢ã«ã³ã
ã·åºãã¢ã«ãã«ããªåºãã¢ã·ã«ãªãã·åºãã«ã«ã
ãã«åºçãæããããã ããããŠããåå¿ã«é¢äžããªã眮æåºãæãã
äžäŸ¡ã®çåæ°ŽçŽ åºããšããŠã¯ãäŸãã°ãïŒâãã
ããã·ãšãã«ãïŒâããããã·ãšãã«ããããã
ã·ã¡ãã«ãïŒâããããã·âïŒâã¡ãã«ãšãã«ã
ïŒâããããã·âïŒâããšãã«ãããã«ãã¢ã»ã
ã«ãããããªãã«ãïŒâãªããœããã«ãã¡ããã·
ã«ã«ããã«ã¡ãã«ãã¡ããã·ã«ã«ããã«ãšãã«ã
ãšããã·ã«ã«ããã«ã¡ãã«ãtertâãããã·ã«ã«
ããã«ã¡ãã«ãã¡ããã·ãšãã«ãã¢ã»ããã·ãšã
ã«ãïŒâã¢ã»ããã·ãããã«ãããã©ããããã©
ãã«ãªãã·ãšãã«åºçãæããããã ããã«R4ãšR5ãšãäžç·ã«ãªã€ãŠè¡šããããšã®
ãããβâã©ã¯ã¿ã ç³»æçç©è³ªããβâã©ã¯ã¿ã
ç°ãé€ããåŸã«æ®ãç°å¡ããšããŠã¯ãäŸãã°ã
æ³ã«é¢ããã ïŒâã¢ãŒããžãã³èªå°äœã¯ãæèæ§ç©è³ªãšããŠ
çŸåšæã泚ç®ãããŠããβâã©ã¯ã¿ã ç³»æçç©è³ª
ã®åºæ¬éªšæ Œããªãååç©ã§ãããäŸãã°ãæçç©
質ãšããŠçŸåšäžå¿çäœçœ®ãå ããŠããããã·ãªã³
ç³»æçç©è³ªãã»ãã¢ãã¹ããªã³ç³»æçç©è³ªã䞊ã³
ã«æ¬¡ã®äžä»£ãã«ãªãæçç©è³ªãšããããŠããããš
ããã€ã·ã³ããã«ã«ãžã·ã³çã¯ããããäžèšåŒ ã§ç€ºãããïŒâã¢ãŒããžãã³éªšæ Œãå«ãã§ããã
ãšã¯ããç¥ãããŠãããšããã§ããã ãã®ãããªïŒâã¢ãŒããžãã³éªšæ Œãå«ãåå
ç©ãããªãã¡ãïŒâã¢ãŒããžãã³èªå°äœãåæã
ãããã®æ¹æ³ã¯åŸæ¥ããããã€ãææ¡ãããŠã
ããäŸãã°ãβâã¢ã©ãã³ã®ãšã¹ãã«ããã°ãªã
ã€ãŒåå¿ã«ããïŒâã¢ãŒããžãã³ãåŸãæ¹æ³ãJ.
Am.Chem.Soc.ã71ã2124ïŒ1949ïŒïŒChem.ïŒ
Ind.ã1964ã2097çåç §ããâ眮æβâã¢ã©ã
ã³ãå¡©åããªãã«â第äžçŽã¢ãã³ã«ããçž®åãã
ãŠïŒâã¢ãŒããžãã³ãåŸãæ¹æ³ãJ.Org.Chem.ã
23ã1102ïŒ1958ïŒçåç §ããβâã¢ããé žèªå°äœã
ãžã·ã¯ãããã·ã«ã«ã«ããžã€ããã§åŠçããŠïŒâ
ã¢ãŒããžãã³èªå°äœãåŸãæ¹æ³ãTetrahedron
Lettersã21ã2783ïŒ1980ïŒïŒJ.Am.Chem.Soc.ã
102ã2060ïŒ1980ïŒçåç §ããªã©ãå ±åãããŠã
ãããããããããåŸæ¥ææ¡ãããŠããæ¹æ³ã¯ã
ãã°ãã°åºè³ªã®æ§é ã«å·Šå³ãããããé«äŸ¡ãªè©Šè¬
ãçšããå¿ èŠããã€ãããåçãäžååã§ãã€ã
ãããçã®äžå©ããããå°åºå·¥æ¥çã«æå¹ãªæ¹æ³
ã§ãããšã¯èšãé£ãã ããããªãããβâã©ã¯ã¿ã ç°ãæããç©è³ªã
å·¥æ¥çã«å®äŸ¡ãªåºçºåæåã³è©Šè¬ãã容æã«è£œé
ããããšãå¯èœãšãªãã°ãçŸåšæ³šç®ãããŠããã
ãšããã€ã·ã³ããã«ã«ãžã·ã³ããªãªãããã¯ã¢ã·
ããçã®Î²âã©ã¯ã¿ã ç³»æçç©è³ªã®å šåæãå¯èœ
ãšãªãããã®å·¥æ¥ç䟡å€ã¯çµ¶å€§ãªãã®ãšãªãããš
ã¯æçœã§ããã ããã§ãæ¬çºæè ãã¯Î²âã¢ããé žååç©ãåº
çºåæãšãããããβâã©ã¯ã¿ã ååç©ãããªã
ã¡ïŒâã¢ãŒããžãã³èªå°äœã«å€ããæ¹æ³ã«ã€ãé
æç 究ãè¡ãªã€ãçµæãã¢ã«ãã«ãããªã«ã®ååš
äžã«çž®åéç°è©Šè¬ãšããŠããªããšãã«ãã¹ãã€ã³
åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ãããªããããã
ãé žåéå è©Šè¬ã䜿çšããã°ãβâã¢ããé žåå
ç©ã極ããŠç°¡åã«å¥œåçã§å¯Ÿå¿ããïŒâã¢ãŒããž
ãã³èªå°äœã«å€ãããããšãèŠãåºããæ¬çºæã
å®æããã«è³ã€ãã ããããŠãæ¬çºæã«åŸãã°ãã¢ããåºãã¢ã眮
æãããŠããŠãããβâã¢ããé žååç©ãã¢ã«ã
ã«ãããªã«ã®ååšäžã«ããªããšãã«ãã¹ãã€ã³å
ã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ã§åŠçããããšãç¹
城ãšããïŒâã¢ãŒããžãã³èªå°äœã®è£œé æ¹æ³ãæ
äŸãããã æ¬çºæã®æ¹æ³ã¯ãã¢ããåºãã¢ã眮æãããŠã
ãŠãããβâã¢ããé žååç©ã«å¯ŸããŠåºãé©çšã
ãããšãã§ããå©ç¹ããããïŒâã¢ãŒããžãã³èª
å°äœã®äžè¬çåææ³ãæäŸãããã®ã§ããã ããããŠãæ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãšã
ãŠäœ¿çšãããã¢ããåºãã¢ã眮æãããŠããŠãã
ãβâã¢ããé žååç©ã¯ãå ·äœçã«ã¯ãäžèšäžè¬
åŒ åŒäžãR1åã³R2ã¯ããããç¬ç«ã«æ°ŽçŽ ååã
ã¢ããåºã眮æã¢ããåºãã¢ã«ã³ãã·åºåã¯åå¿
ã«é¢äžããªã眮æåºãæããŠããŠãããäžäŸ¡ã®ç
åæ°ŽçŽ åºãè¡šãããR3åã³R4ã¯ããããç¬ç«ã«
æ°ŽçŽ åååã¯åå¿ã«é¢äžããªã眮æåºãæããŠã
ãŠãããäžäŸ¡ã®çåæ°ŽçŽ åºãè¡šãããR5ã¯æ°ŽçŽ
åååã¯äžäŸ¡ã®çåæ°ŽçŽ åºãè¡šãããæãã¯R4
ãšR5ãšã¯äžç·ã«ãªã€ãŠÎ²âã©ã¯ã¿ã ç³»æçç©è³ª
ããβâã©ã¯ã¿ã ç°ãé€ããåŸã«æ®ãç°å¡ãè¡šã
ããŠãããã ã§ç€ºãããååç©ãå å«ããã äžèšåŒïŒïŒã«ãããŠãR1åã³ïŒåã¯R2ã«ã
ã€ãŠè¡šããããã眮æã¢ããåºããšããŠã¯ãäŸã
ã°ããã³ãžã«ã¢ãããããªããšãã«ã¡ãã«ã¢ãã
åºçã®ã¢ã©ã«ãã«ã¢ããåºïŒãã³ãžã«ãªãã·ã«ã«
ããã«ã¢ãããtertâãããã·ã«ã«ããã«ã¢ãã
åºçã®ã¢ã©ã«ãã«ïŒåã¯ã¢ã«ãã«ïŒãªãã·ã«ã«ã
ãã«ã¢ããåºïŒã¢ã»ãã«ã¢ããåºçã®ã¢ã«ã«ãã€
ã«ã¢ããåºïŒããšãã«ã¢ã»ãã«ã¢ãããããšãã
ã·ã¢ã»ãã«ã¢ãããαâããããã·ããšãã«ã¢ã»
ãã«ã¢ãããαâã¹ã«ãããšãã«ã¢ã»ãã«ã¢ãã
åºçã®ã¢ã©ã«ã«ãã€ã«ã¢ããåºïŒïŒâããšãã«ã¢
ã»ãã«ã¢ãããïŒâïŒ1HïŒâããã©ãŸãªã«ã¢ã»
ãã«ã¢ãããïŒïŒâããªãžã«ããªïŒã¢ã»ãã«ã¢ã
ããïŒïŒâã¢ããâïŒâãã¢ãŸãªã«ïŒã¢ã»ãã«ã¢
ããåºçãžã®ãããã¢ã©ã«ã«ãã€ã«ã¢ããåºïŒã·
ã¢ãã¢ã»ãã«ã¢ããåºãαâã¡ããã·ã€ããâïŒ
âããªã«ã¢ã»ãã«ã¢ããåºçãæãããããŸãã
ãã¢ã«ã³ãã·åºããšããŠã¯ãäŸãã°ãã¡ããã·ã
ãšããã·ãïœâãããã¯isoâããããã·ãïœâã
isoâãsecâãããã¯tertâãããã·åºçã®äœçŽ
ã¢ã«ã³ãã·åºã奜é©ã§ããã R1ãR5ã«ãã€ãŠè¡šãããããäžäŸ¡ã®çåæ°ŽçŽ
åºãã¯éç¶ãç°ç¶ïŒè³éŠç°ç¶åã¯èç°åŒã®ããã
ãã§ãã€ãŠãããïŒåã³ãããã®çµåããã®ãã
ããã§ãã€ãŠããããäžè¬ã«10å以äžã®ççŽ åå
ãå«æãããã®ã奜é©ã§ãããç¹ã«ã¯é£œåããŠã
ããã®ãæãŸããããããäžäŸ¡ã®çåæ°ŽçŽ åºã®å ·
äœäŸãšããŠã¯ãå ·äœçã«ã¯ãã¢ã«ãã«åºãäŸãã°
ã¡ãã«ããšãã«ãïœâãããã¯isoâãããã«ã
ïœâãisoâãsecâãããã¯tertâããã«åºçã®
äœçŽã¢ã«ãã«åºïŒã¢ãªã«åºçã®ã¢ã«ã±ãã«åºïŒãš
ããã«åºçã®ã¢ã«ããã«åºïŒã·ã¯ãããã·ã«ãã·
ã¯ããããã«åºçã®ã·ã¯ãã¢ã«ãã«åºïŒããšã
ã«ããããã«åºçã®ã¢ãªãŒã«åºïŒãã³ãžã«ãããš
ããã«ãããšãã«ãããã«åºçã®ã¢ã©ã«ãã«åºç
ãæããããã ãŸãããããäžäŸ¡ã®çåæ°ŽçŽ åºäžã«ååšããã
ãåå¿ã«é¢äžããªã眮æåºããšããŠã¯ãäŸãã°ã
æ°Žé žåºãäœçŽã¢ã«ã³ãã·ã«ã«ããã«åºãã¢ã«ã³ã
ã·åºãã¢ã«ãã«ããªåºãã¢ã·ã«ãªãã·åºãã«ã«ã
ãã«åºçãæããããã ããããŠããåå¿ã«é¢äžããªã眮æåºãæãã
äžäŸ¡ã®çåæ°ŽçŽ åºããšããŠã¯ãäŸãã°ãïŒâãã
ããã·ãšãã«ãïŒâããããã·ãšãã«ããããã
ã·ã¡ãã«ãïŒâããããã·âïŒâã¡ãã«ãšãã«ã
ïŒâããããã·âïŒâããšãã«ãããã«ãã¢ã»ã
ã«ãããããªãã«ãïŒâãªããœããã«ãã¡ããã·
ã«ã«ããã«ã¡ãã«ãã¡ããã·ã«ã«ããã«ãšãã«ã
ãšããã·ã«ã«ããã«ã¡ãã«ãtertâãããã·ã«ã«
ããã«ã¡ãã«ãã¡ããã·ãšãã«ãã¢ã»ããã·ãšã
ã«ãïŒâã¢ã»ããã·ãããã«ãããã©ããããã©
ãã«ãªãã·ãšãã«åºçãæããããã ããã«R4ãšR5ãšãäžç·ã«ãªã€ãŠè¡šããããšã®
ãããβâã©ã¯ã¿ã ç³»æçç©è³ªããβâã©ã¯ã¿ã
ç°ãé€ããåŸã«æ®ãç°å¡ããšããŠã¯ãäŸãã°ã
ãåŒã
ãåŒã
ãåŒãçãæãã
ããšãã§ããã
ããã§ããäœçŽããªãèªã¯ãã®èªãä»ãããåº
åã¯ååç©ãïŒå以äžã奜ãŸããã¯ïŒå以äžã®ç
çŽ ååãæããããšãæå³ããã æ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãšããŠäœ¿çšãã
ãåèšåŒïŒïŒã®ååç©ã®ä»£è¡šäŸãåæããã°æ¬¡
ã®ãšããã§ããã βâã¢ã©ãã³ãαâã¡ããã·âβâã¢ã©ãã³ã
αâã¢ããâβâã¢ã©ãã³ãαâïŒïŒâãããã
ã·ãšãã«ïŒâβâã¢ã©ãã³ãαâãšãã«âβâã¢
ã©ãã³ãαâã¢ããâβâïŒïŒâããããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâïŒïŒâããããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâïŒïŒâã¢ã»ããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâããšãã«âβâã¢ã©ã
ã³ãâãã³ãžã«âβâã¢ã©ãã³ãβâã¢ããã°
ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ãβâã¢ããã°ã«ã¿
ã«é žã¢ããšãã«ãšã¹ãã«ãβâã¢ããã°ã«ã¿ã«é ž
ã¢ãâtertâããã«ãšã¹ãã«çã æ¬çºæã®æ¹æ³ã¯ãäžèšããåŠãβâã¢ããé žå
åç©ããã¢ã«ãã«ãããªã«ã®ååšäžã«ããªããšã
ã«ãã¹ãã€ã³åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ãçž®
åå€ãšããŠçšããŠéç°ãããŠå¯Ÿå¿ããäžèšäžè¬åŒ
ïŒïŒã§ç€ºãããïŒâã¢ãŒããžãã³èªå°äœã圢æ
ããåå¿ã§ããã äžèšéç°åå¿ã«ãããŠçž®åå€ãšããŠããªããšã
ã«ãã¹ãã€ã³ãšçµåãããŠäœ¿çšãããè€çŽ ç°ãžã¹
ã«ãã€ãååç©ãšããŠã¯ãäŸãã°ãïŒïŒ2â²âãžã
ãªãžã«ãžã¹ã«ãã€ããïŒïŒ2â²âãã³ãŸãã¢ãŸãªã«
ãžã¹ã«ãã€ããïŒïŒ2â²âãžãã³ãºã€ãããŸãªã«ãž
ã¹ã«ãã€ããïŒïŒ4â²âãžããªãžã«ãžã¹ã«ãã€ãç
ãæããããããŸããçž®åå€ãšããŠçšããããªã
ãšãã«ãã¹ãã€ã³åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©
ã®äœ¿çšéã¯èšççã§ã¯ãªããçšããåºçºåæã®çš®
é¡ãåå¿æ¡ä»¶çã«ããåºãå€ããããšãã§ãã
ããäžè¬ã«ã¯çšããβâã¢ããé žååç©ïŒã¢ã«ã«
察ããŠå°ãªããšã1.0ã¢ã«ã奜ãŸããã¯1.0ã1.3ã¢
ã«ã®ç¯å²ã§äœ¿çšããããšãæãŸããããŸããããª
ããšãã«ãã¹ãã€ã³ãšè€çŽ ç°ãžã¹ã«ãã€ãååç©
ã¯äžè¬ã«çã¢ã«æ¯ã§äœ¿çšãããã ãã®ããªããšãã«ãã¹ãã€ã³ãšè€çŽ ç°ãžã¹ã«ã
ã€ãååç©ãšã®çµåããè©Šè¬ã䜿çšããäžèšã®é
ç°åå¿ã¯ããããè©Šè¬ãçšããå Žåã®ããèªäœå ¬
ç¥ã®åå¿æ段ãäŸãã°ãTetrahedron Lettersã
1970ã1901åç §ãã«æºããŠè¡ãªãããšãã§ããã ãŸããæ¬çºæã«ããã°ãäžèšéç°åå¿ã¯ãããª
ã«ååç©ãæ®ã«ã¢ã«ãã«ãããªã«ã®ååšäžã«å®æœ
ãããšãã«ã¯ãéåžžã«åæ»ã«äžã€é«åçã§é²è¡ã
ãããšãèŠãåºãããã䜿çšãããã¢ã«ãã«ãã
ãªã«ãšããŠã¯ãäŸãã°ã¢ã»ããããªã«ãããããª
ãããªã«çãæããããäžã§ãã¢ã»ããããªã«ã
æé©ã§ããã ãããã¢ã«ãã«ãããªã«ã®äœ¿çšéã«ã¯ç¹ã«å¶é
ã¯ãªããçšããåºçºåæã®çš®é¡ãåå¿æ¡ä»¶çã«å¿
ããŠåºç¯ã«å€ããããšãã§ããããäžè¬ã«ã¯çšã
ãβâã¢ããé žååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšã
ïŒã¢ã«ã奜ãŸããã¯10ã¢ã«ä»¥äžã®éã§äœ¿çšããã
ãšãæãŸãããæ®ã«ãã¢ã«ãã«ãããªã«ã¯å€§éå°
çšããããšã«ããããèªèº«æº¶åªãšããŠã®åœ¹å²ãæ
ãããããã«ããããšã奜ãŸããããããå¿è«ã
ãã®ä»ã®æº¶åªã䜵çšããããšãå¯èœã§ããã䜿çš
ããã溶åªãšããŠã¯ãäŸãã°ããžã¯ããã¡ã¿ã³ç
ã®ããã²ã³åçåæ°ŽçŽ é¡ïŒãžãšãã«ãšãŒãã«ãã
ãã©ããããã©ã³ããžãªããµã³çã®ãšãŒãã«é¡ïŒ
ãžã¡ãã«ãã«ã ã¢ããïŒãžã¡ãã«ã¹ã«ããã·ãïŒ
é ¢é žãšãã«çã®ãšã¹ãã«é¡ïŒãã³ãŒã³ããã«ãšã³
çã®è³éŠæçåæ°ŽçŽ é¡ïŒæ°ŽïŒã¡ã¿ããŒã«ããšã¿ã
ãŒã«çã®ã¢ã«ã³ãŒã«é¡ãã·ã¯ããããµã³çã®ã·ã¯
ãã¢ã«ã«ã³é¡ïŒã¢ã»ãã³çã®ã±ãã³é¡çãæãã
ããšãã§ããã äžèšéç°åå¿ã®æž©åºŠã¯èšççã§ã¯ãªãåºç¯ã«å€
ããããšãã§ããããäžè¬ã«ã¯åžžæž©ä¹è³åå¿æ··å
ç©ã®æ²žç¹éã®æž©åºŠãæ®ã«éæµæž©åºŠã奜é©ã§ããã
ãŸããäžèšåå¿ã¯åžžå§ãæžå§ãå å§ã®ãããã®æ¡
件äžã§è¡ãªãããšãå¯èœã§ããã ãªããäžèšÎ²âã©ã¯ã¿ã ç°ã®åœ¢æïŒéç°ïŒåå¿
ã¯ãåå¿ç³»äžã®åºçºåæãããªãã¡Î²âã¢ããé ž
ååç©ã®æ¿åºŠã«ãã圱é¿ãåããäžè¬ã«æ¿åºŠãé«
ããããšç®çãšããïŒâã¢ãŒããžãã³èªå°äœã®å
çãäœäžããåŸåãããããšãå€æãããããã
ãŠã該βâã¢ããé žååç©ã¯ãäžè¬ã«åå¿ç³»äžçŽ
0.001ãçŽ1Mã奜ãŸããã¯çŽ0.01ãçŽ0.1Mã®ç¯å²
å ã®æ¿åºŠã§ååšããããããšãæå©ã§ãããåŸã€
ãŠãæ¬çºæã®æ¹æ³ãå®æœããã«éããŠã¯ã該βâ
ã¢ããé žååç©ã滎äžããããšã«ããåå¿ç³»äžã«
ããã該ååç©ã®æ¿åºŠã調ç¯ããªããåå¿ãè¡ãª
ãããšãå¯èœã§ããã åå¿çµäºåŸã®åå¿æ··åç©äžããã®ç®çãšããå
èšåŒïŒïŒã®ïŒâã¢ãŒããžãã³èªå°äœã®åé¢åã³
粟補ã¯ããèªäœå ¬ç¥ã®æ段ãäŸãã°ãæœåºãã¯ã
ããã°ã©ãã€ãŒãåçµæ¶çã«ããè¡ãªãããšãã§
ããã æ¬çºæã®æ¹æ³ã«ããã°ãåèšåŒïŒïŒã®ïŒâã¢
ãŒããžãã³èªå°äœã奜åçã§åŸããããã®ç®çç
æç©ã¯ãåè¿°ããããã«ãβâã©ã¯ã¿ã ç³»æçç©
質ã®åæäžéäœãšããŠæ¥µããŠæçšã§ãããäŸã
ã°ãæ¬çºæã®æ¹æ³ã«ãã€ãŠè£œé ãããäžèšåŒïŒ
âïœïŒã®ïŒâäœçŽã¢ã«ã³ãã·ã«ã«ããã«ã¡ãã«â
ïŒâã¢ãŒããžãã³ããããšããã€ã·ã³ãåæãã
çµè·¯ãåå¿åŒã§ç€ºãã°æ¬¡ã®ãšããã§ããã 以äžã«è¿°ã¹ãæ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãš
ããŠäœ¿çšããåèšåŒïŒïŒã®Î²âã¢ããé žååç©
ã¯å€§éšåã¯æ¢ç¥ã§ããããäžéšã¯æ°èŠãªãã®ãå«
ãŸããŠãããäŸãã°ãåèšäžè¬åŒïŒïŒã«ãã
ãŠãR1ãR2ãR3åã³R5ãå ±ã«æ°ŽçŽ ååãè¡šãã
äžã€R4ãäœçŽã¢ã«ã³ãã·ã«ã«ããã«ã¡ãã«åºã
è¡šããååç©ãããªãã¡äžèšåŒ åŒäžãã¯äœçŽã¢ã«ãã«åºãè¡šããã ã§ç€ºãããååç©ã¯æç®æªèŒã®æ°èŠååç©ã§ã
ãããã®ãã®ã¯äŸãã°ãã¢ããåºããã³ãžã«ãªã
ã·ã«ã«ããã«åºã§ä¿è·ãããŠããŠãããβâã¢ã
ãã°ã«ã¿ã³é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãã«ã«
ãã³é žãšã¹ãã«å æ°Žåè§£é µçŽ ã«ããå æ°Žå解ã«ä»
ããïŒåã®ã¢ã«ãã«ãšã¹ãã«åºã®ãã¡ã®ïŒåã®ã¿
ãéžæçã«å æ°Žå解ããããšã«ãã補é ããããš
ãã§ããããã®å Žåãã¢ããåºãéé¢ã®Î²âã¢ã
ãã°ã«ã¿ã«é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ã䜿çš
ããã°å åŠæŽ»æ§Î²âïŒïŒ²ïŒâã¢ããã°ã«ã¿ã«é žã¢
ãïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãåŸãããä»æ¹ãã¢
ããåºããã³ãžã«ãªãã·ã«ã«ããã«åºã§ä¿è·ãã
ãβâã¢ããã°ã«ã¿ã«é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹
ãã«ã䜿çšããã°å åŠæŽ»æ§Î²âïŒïŒ³ïŒâã¢ããã°
ã«ã¿ã«é žã¢ãïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãåŸãã
ãã ãã®ããã«ããŠè£œé ãããäžèšåŒïŒâïœïŒã®
ååç©ã«å¯ŸããŠæ¬çºæã®æ¹æ³ãé©çšããããšã«ã
ã€ãŠåŸãããäžèšåŒ åŒäžãã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ããŸãæ°èŠãªååç©ã§ãããçš
ããåŒïŒâïœïŒã®ååç©ã®ç«äœé 眮ã«å¯Ÿå¿ãã
äžèšã®ïŒã€ã®ç«äœé 眮ããšãããã
åã¯ååç©ãïŒå以äžã奜ãŸããã¯ïŒå以äžã®ç
çŽ ååãæããããšãæå³ããã æ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãšããŠäœ¿çšãã
ãåèšåŒïŒïŒã®ååç©ã®ä»£è¡šäŸãåæããã°æ¬¡
ã®ãšããã§ããã βâã¢ã©ãã³ãαâã¡ããã·âβâã¢ã©ãã³ã
αâã¢ããâβâã¢ã©ãã³ãαâïŒïŒâãããã
ã·ãšãã«ïŒâβâã¢ã©ãã³ãαâãšãã«âβâã¢
ã©ãã³ãαâã¢ããâβâïŒïŒâããããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâïŒïŒâããããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâïŒïŒâã¢ã»ããã·ãšã
ã«ïŒâβâã¢ã©ãã³ãβâããšãã«âβâã¢ã©ã
ã³ãâãã³ãžã«âβâã¢ã©ãã³ãβâã¢ããã°
ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ãβâã¢ããã°ã«ã¿
ã«é žã¢ããšãã«ãšã¹ãã«ãβâã¢ããã°ã«ã¿ã«é ž
ã¢ãâtertâããã«ãšã¹ãã«çã æ¬çºæã®æ¹æ³ã¯ãäžèšããåŠãβâã¢ããé žå
åç©ããã¢ã«ãã«ãããªã«ã®ååšäžã«ããªããšã
ã«ãã¹ãã€ã³åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©ãçž®
åå€ãšããŠçšããŠéç°ãããŠå¯Ÿå¿ããäžèšäžè¬åŒ
ïŒïŒã§ç€ºãããïŒâã¢ãŒããžãã³èªå°äœã圢æ
ããåå¿ã§ããã äžèšéç°åå¿ã«ãããŠçž®åå€ãšããŠããªããšã
ã«ãã¹ãã€ã³ãšçµåãããŠäœ¿çšãããè€çŽ ç°ãžã¹
ã«ãã€ãååç©ãšããŠã¯ãäŸãã°ãïŒïŒ2â²âãžã
ãªãžã«ãžã¹ã«ãã€ããïŒïŒ2â²âãã³ãŸãã¢ãŸãªã«
ãžã¹ã«ãã€ããïŒïŒ2â²âãžãã³ãºã€ãããŸãªã«ãž
ã¹ã«ãã€ããïŒïŒ4â²âãžããªãžã«ãžã¹ã«ãã€ãç
ãæããããããŸããçž®åå€ãšããŠçšããããªã
ãšãã«ãã¹ãã€ã³åã³è€çŽ ç°ãžã¹ã«ãã€ãååç©
ã®äœ¿çšéã¯èšççã§ã¯ãªããçšããåºçºåæã®çš®
é¡ãåå¿æ¡ä»¶çã«ããåºãå€ããããšãã§ãã
ããäžè¬ã«ã¯çšããβâã¢ããé žååç©ïŒã¢ã«ã«
察ããŠå°ãªããšã1.0ã¢ã«ã奜ãŸããã¯1.0ã1.3ã¢
ã«ã®ç¯å²ã§äœ¿çšããããšãæãŸããããŸããããª
ããšãã«ãã¹ãã€ã³ãšè€çŽ ç°ãžã¹ã«ãã€ãååç©
ã¯äžè¬ã«çã¢ã«æ¯ã§äœ¿çšãããã ãã®ããªããšãã«ãã¹ãã€ã³ãšè€çŽ ç°ãžã¹ã«ã
ã€ãååç©ãšã®çµåããè©Šè¬ã䜿çšããäžèšã®é
ç°åå¿ã¯ããããè©Šè¬ãçšããå Žåã®ããèªäœå ¬
ç¥ã®åå¿æ段ãäŸãã°ãTetrahedron Lettersã
1970ã1901åç §ãã«æºããŠè¡ãªãããšãã§ããã ãŸããæ¬çºæã«ããã°ãäžèšéç°åå¿ã¯ãããª
ã«ååç©ãæ®ã«ã¢ã«ãã«ãããªã«ã®ååšäžã«å®æœ
ãããšãã«ã¯ãéåžžã«åæ»ã«äžã€é«åçã§é²è¡ã
ãããšãèŠãåºãããã䜿çšãããã¢ã«ãã«ãã
ãªã«ãšããŠã¯ãäŸãã°ã¢ã»ããããªã«ãããããª
ãããªã«çãæããããäžã§ãã¢ã»ããããªã«ã
æé©ã§ããã ãããã¢ã«ãã«ãããªã«ã®äœ¿çšéã«ã¯ç¹ã«å¶é
ã¯ãªããçšããåºçºåæã®çš®é¡ãåå¿æ¡ä»¶çã«å¿
ããŠåºç¯ã«å€ããããšãã§ããããäžè¬ã«ã¯çšã
ãβâã¢ããé žååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšã
ïŒã¢ã«ã奜ãŸããã¯10ã¢ã«ä»¥äžã®éã§äœ¿çšããã
ãšãæãŸãããæ®ã«ãã¢ã«ãã«ãããªã«ã¯å€§éå°
çšããããšã«ããããèªèº«æº¶åªãšããŠã®åœ¹å²ãæ
ãããããã«ããããšã奜ãŸããããããå¿è«ã
ãã®ä»ã®æº¶åªã䜵çšããããšãå¯èœã§ããã䜿çš
ããã溶åªãšããŠã¯ãäŸãã°ããžã¯ããã¡ã¿ã³ç
ã®ããã²ã³åçåæ°ŽçŽ é¡ïŒãžãšãã«ãšãŒãã«ãã
ãã©ããããã©ã³ããžãªããµã³çã®ãšãŒãã«é¡ïŒ
ãžã¡ãã«ãã«ã ã¢ããïŒãžã¡ãã«ã¹ã«ããã·ãïŒ
é ¢é žãšãã«çã®ãšã¹ãã«é¡ïŒãã³ãŒã³ããã«ãšã³
çã®è³éŠæçåæ°ŽçŽ é¡ïŒæ°ŽïŒã¡ã¿ããŒã«ããšã¿ã
ãŒã«çã®ã¢ã«ã³ãŒã«é¡ãã·ã¯ããããµã³çã®ã·ã¯
ãã¢ã«ã«ã³é¡ïŒã¢ã»ãã³çã®ã±ãã³é¡çãæãã
ããšãã§ããã äžèšéç°åå¿ã®æž©åºŠã¯èšççã§ã¯ãªãåºç¯ã«å€
ããããšãã§ããããäžè¬ã«ã¯åžžæž©ä¹è³åå¿æ··å
ç©ã®æ²žç¹éã®æž©åºŠãæ®ã«éæµæž©åºŠã奜é©ã§ããã
ãŸããäžèšåå¿ã¯åžžå§ãæžå§ãå å§ã®ãããã®æ¡
件äžã§è¡ãªãããšãå¯èœã§ããã ãªããäžèšÎ²âã©ã¯ã¿ã ç°ã®åœ¢æïŒéç°ïŒåå¿
ã¯ãåå¿ç³»äžã®åºçºåæãããªãã¡Î²âã¢ããé ž
ååç©ã®æ¿åºŠã«ãã圱é¿ãåããäžè¬ã«æ¿åºŠãé«
ããããšç®çãšããïŒâã¢ãŒããžãã³èªå°äœã®å
çãäœäžããåŸåãããããšãå€æãããããã
ãŠã該βâã¢ããé žååç©ã¯ãäžè¬ã«åå¿ç³»äžçŽ
0.001ãçŽ1Mã奜ãŸããã¯çŽ0.01ãçŽ0.1Mã®ç¯å²
å ã®æ¿åºŠã§ååšããããããšãæå©ã§ãããåŸã€
ãŠãæ¬çºæã®æ¹æ³ãå®æœããã«éããŠã¯ã該βâ
ã¢ããé žååç©ã滎äžããããšã«ããåå¿ç³»äžã«
ããã該ååç©ã®æ¿åºŠã調ç¯ããªããåå¿ãè¡ãª
ãããšãå¯èœã§ããã åå¿çµäºåŸã®åå¿æ··åç©äžããã®ç®çãšããå
èšåŒïŒïŒã®ïŒâã¢ãŒããžãã³èªå°äœã®åé¢åã³
粟補ã¯ããèªäœå ¬ç¥ã®æ段ãäŸãã°ãæœåºãã¯ã
ããã°ã©ãã€ãŒãåçµæ¶çã«ããè¡ãªãããšãã§
ããã æ¬çºæã®æ¹æ³ã«ããã°ãåèšåŒïŒïŒã®ïŒâã¢
ãŒããžãã³èªå°äœã奜åçã§åŸããããã®ç®çç
æç©ã¯ãåè¿°ããããã«ãβâã©ã¯ã¿ã ç³»æçç©
質ã®åæäžéäœãšããŠæ¥µããŠæçšã§ãããäŸã
ã°ãæ¬çºæã®æ¹æ³ã«ãã€ãŠè£œé ãããäžèšåŒïŒ
âïœïŒã®ïŒâäœçŽã¢ã«ã³ãã·ã«ã«ããã«ã¡ãã«â
ïŒâã¢ãŒããžãã³ããããšããã€ã·ã³ãåæãã
çµè·¯ãåå¿åŒã§ç€ºãã°æ¬¡ã®ãšããã§ããã 以äžã«è¿°ã¹ãæ¬çºæã®æ¹æ³ã«ãããŠåºçºåæãš
ããŠäœ¿çšããåèšåŒïŒïŒã®Î²âã¢ããé žååç©
ã¯å€§éšåã¯æ¢ç¥ã§ããããäžéšã¯æ°èŠãªãã®ãå«
ãŸããŠãããäŸãã°ãåèšäžè¬åŒïŒïŒã«ãã
ãŠãR1ãR2ãR3åã³R5ãå ±ã«æ°ŽçŽ ååãè¡šãã
äžã€R4ãäœçŽã¢ã«ã³ãã·ã«ã«ããã«ã¡ãã«åºã
è¡šããååç©ãããªãã¡äžèšåŒ åŒäžãã¯äœçŽã¢ã«ãã«åºãè¡šããã ã§ç€ºãããååç©ã¯æç®æªèŒã®æ°èŠååç©ã§ã
ãããã®ãã®ã¯äŸãã°ãã¢ããåºããã³ãžã«ãªã
ã·ã«ã«ããã«åºã§ä¿è·ãããŠããŠãããβâã¢ã
ãã°ã«ã¿ã³é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãã«ã«
ãã³é žãšã¹ãã«å æ°Žåè§£é µçŽ ã«ããå æ°Žå解ã«ä»
ããïŒåã®ã¢ã«ãã«ãšã¹ãã«åºã®ãã¡ã®ïŒåã®ã¿
ãéžæçã«å æ°Žå解ããããšã«ãã補é ããããš
ãã§ããããã®å Žåãã¢ããåºãéé¢ã®Î²âã¢ã
ãã°ã«ã¿ã«é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ã䜿çš
ããã°å åŠæŽ»æ§Î²âïŒïŒ²ïŒâã¢ããã°ã«ã¿ã«é žã¢
ãïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãåŸãããä»æ¹ãã¢
ããåºããã³ãžã«ãªãã·ã«ã«ããã«åºã§ä¿è·ãã
ãβâã¢ããã°ã«ã¿ã«é žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹
ãã«ã䜿çšããã°å åŠæŽ»æ§Î²âïŒïŒ³ïŒâã¢ããã°
ã«ã¿ã«é žã¢ãïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«ãåŸãã
ãã ãã®ããã«ããŠè£œé ãããäžèšåŒïŒâïœïŒã®
ååç©ã«å¯ŸããŠæ¬çºæã®æ¹æ³ãé©çšããããšã«ã
ã€ãŠåŸãããäžèšåŒ åŒäžãã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ããŸãæ°èŠãªååç©ã§ãããçš
ããåŒïŒâïœïŒã®ååç©ã®ç«äœé 眮ã«å¯Ÿå¿ãã
äžèšã®ïŒã€ã®ç«äœé 眮ããšãããã
ãåŒã
ãåŒã
ãããã®ãã¡åŒïŒâïœâïŒïŒã®ïŒ³âç°æ§äœã¯
åè¿°ããåæçµè·¯ãçµãŠããšããã€ã·ã³ã補é ã
ãããã«æ®ã«æçšã§ããã 以äžãå®æœäŸãæ²ããŠæ¬çºæãããã«èª¬æã
ãã å®æœäŸ ïŒ Î²âïŒïŒ³ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹
ãã«165mgïŒ1.02ããªã¢ã«ïŒãã¢ã»ããããªã«20
mlã«æžæ¿ããããªããšãã«ãã¹ãã€ã³315mg
ïŒ1.20ããªã¢ã«ïŒãšããžããªãžã«ãžã¹ã«ãã€ã264
mgïŒ1.20ããªã¢ã«ïŒãšãå ããã®ã¡æ¹æãã€ã€12
æé55â60âã«å æž©ãããåå¿ãé²ãã«ã€ããŠæº¶
液ã¯é»è²ã«çè²ããŠããã åå¿åŸæº¶æ¶²ãæžå§æ¿çž®ããæ®æž£ãã·ãªã«ã²ã«40
ïœã®ã«ã©ã ã«è² è·ãããšãŒãã«âå¡©åã¡ãã¬ã³
ïŒïŒïŒïŒïŒã§æº¶åºãããç®çç©ãå«ããã©ã¯ã·ãš
ã³ãã·ãªã«ã²ã«20ïœã§åã³ã¯ãããã°ã©ãã€ãŒã«
ãããŠãç®çã®ïŒâïŒïŒ³ïŒâã¡ããã·ã«ã«ããã«
ã¡ãã«âïŒâã¢ãŒããžãã³123mgïŒåç84ïŒ ïŒã
çµæ¶ãšããŠåŸãã äžèšçæç©ã®èµ€å€åžåã¹ãã¯ãã«ãæ žç£æ°å ±é³Ž
ã¹ãã¯ãã«ããã¹ã¹ãã¯ãã«åã³æå 床ã¯æ¬¡ã®é
ãã§ããã IRïŒ3420ã1765ïŒÎ²âã©ã¯ã¿ã ïŒã1740cm-1ã NMRïŒ2.4ã2.9ïŒïœã3HãCH2COOCH3ãšC3â
ïŒã3.16ïŒdddïŒïŒªïŒïŒãïŒã15HzïŒã1HãC3â
ïŒ37.2ïŒïœã3HãCOOCH3ïŒã3.95ïŒïœã1HãC4
âïŒã6.15ïŒbrã1HãâïŒã ãαã25 DïŒ65.34ãïŒïœïŒ1.11ãCHCl3ïŒ M+ïŒïŒïŒ144 äžèšæ¹æ³ã«ãããŠåºçºåæãšããŠçšããβâ
ïŒïŒ³ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã¯
次ã®ããã«ããŠè£œé ããã ã€ïŒ βâã¢ããã°ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã« 4.68ïœïŒ26.7ããªã¢ã«ïŒã®ãžãªããµã³æº¶æ¶²ïŒ40
mlïŒã«ããã³ãžã«ãªãã·ã«ã«ããã«ã¯ããªã5.47
ïœïŒ32.1ããªã¢ã«ïŒã®ãžãªããµã³æº¶æ¶²ïŒ20mlïŒãš
ããªãšãã«ã¢ãã³3.25ïœïŒ32.1ããªã¢ã«ïŒã®ãžãª
ããµã³æº¶æ¶²ïŒ20mlïŒã滎äžãã宀枩ã§ïŒæéæ¹æ
ãããæåºããçµæ¶ãå¥ãã液ãæ¿çž®ãã·ãª
ã«ã²ã«ã«ã©ã ã¯ãããã°ã©ãã€ã§ç²Ÿè£œãããšãβ
âãã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°ã«ã¿ã«é žãž
ã¡ãã«ãšã¹ãã«7.41ïœïŒåç90ïŒ ïŒãæ²¹ç¶ç©ãšã
ãŠåŸãã ãïŒ Î²âãã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°
ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã«465mgïŒ1.5ããªã¢ã«ïŒ
ãã¢ã»ãã³1.5mlã«æº¶ãããpH8.0ãªã³é žç·©è¡æ¶²45
mlãå ãããè±ã®èèããåŸããããšã¹ãã©ãŒãŒ
ïŒé µçŽ çªå·ïŒEC3.1.1.1.ïŒã·ã°ã瀟ãâ3128ïŒã
èçœéãšããŠ2.7mgãå ãã25âã§ïŒæéãæã
æ¹æããªããæŸçœ®ããã2Nå¡©é ž2.5mlãå ãã溶
液ã®pHãçŽïŒã«èª¿ç¯ããå¡©åã¡ãã¬ã³ã§æœåºã
ããç¡æ°Žç¡«é žãããªãŠã ã§ä¹Ÿç¥åŸãæ¿çž®ãããšç²
çµæ¶419mgãåŸããã·ãªã«ã²ã«ã«ã©ã ã¯ãããã°
ã©ãã€ãŒã§ç²Ÿè£œãããšå åŠæŽ»æ§ã®Î²âïŒïŒ³ïŒâã
ã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°ã«ã¿ã«é žã¢ãã¡
ãã«ãšã¹ãã«410mgïŒåç93ïŒ ïŒãçµæ¶ãšããŠåŸ
ãã èç¹ïŒãšãŒãã«ããåçµæ¶ïŒïŒ97ã97.5âIR
ïŒKBrïŒïŒ3330ã2840ã2960ã1740ã1725ã1700
cm-1ã NMRïŒCDCl3ïŒïŒ2.69ïŒbdã4HãCH2ãïŒ
6HzïŒã3.65ïŒïœã3HãCO2CH3ïŒã4.17ã4.53ïŒïœã
1HãCHïŒã5.07ïŒïœã2HãCH2PhïŒã5.63ïŒbdã
1HãNHïŒã7.30ïŒïœã5HãPhïŒã ãαã25 DïŒ0.71ãïŒïœïŒ7.45ãCHCl3ïŒ ãã®Î²âïŒïŒ³ïŒâãã³ãžã«ãªãã·ã«ã«ããã«ã¢
ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«385mgïŒ1.3ã
ãªã¢ã«ïŒãã¡ã¿ããŒã«20mlã«æº¶ããã10ïŒ ãã©ãž
ãŠã âççŽ 40mgãå ããæ°ŽçŽ é°å²æ°äž30åæ¹æã
ããåå¿æº¶æ¶²ãéåŸæ¿çž®ãããšÎ²âïŒïŒ³ïŒâã¢
ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã®æ²¹ç¶ç©205
mgïŒåç98ïŒ ïŒãåŸããIRïŒ3440ã2400ã2900ã
1730cm-1ã NMRïŒD2OïŒïŒ2.59ïŒbdã2HãïŒ6HzïŒã2.84
ïŒbdã2HãïŒ6HzïŒã3.76ïŒïœã3HãCO2CH3ïŒã
3.85ã4.05ïŒïœã1HãCHïŒã ãαã25 Dâ5.52ãïŒïœïŒ3.26ãH2OïŒã å®æœäŸ ïŒ Î²âïŒïŒ²ïŒÎ²âã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãš
ã¹ãã«57mgïŒ0.35ããªã¢ã«ïŒãããªããšãã«ãã¹
ãã€ã³110mgïŒ0.42ããªã¢ã«ïŒããžããªãžã«ãžã¹ã«
ãã€ã93mgïŒ0.42ããªã¢ã«ïŒãã¢ã»ããããªã«ïŒ
mläžã«ãŠå®æœäŸïŒãšåæ§ã«åå¿ãè¡ãªããåå¿æ··
åç©ãã·ãªã«ã²ã«15ïœã®ã«ã©ã ã¯ãããã°ã©ãã€
ãŒã§ç²Ÿè£œãããšãç®çã®ïŒâïŒïŒ²ïŒâã¡ããã·ã«
ã«ããã«ã¡ãã«âïŒâã¢ãŒããžãã³37mgïŒåç73
ïŒ ïŒãåŸãã IRïŒ3420ã1765ïŒÎ²âã©ã¯ã¿ã ïŒã1740cm-1ã NMRïŒ2.4ã2.9ïŒïœã3HãCH2COOCH3ãšC3â
ïŒã3.16ïŒ1HãC3âïŒã3.72ïŒïœã3Hãâ
COOCH3ïŒã3.95ïŒïœã1HãC4âïŒã6.15ïŒbrã
1HãâïŒã ãαã25 Dâ26.03ãïŒïœïŒ1.26ãCHCl3ïŒM+ïŒïŒïŒ
144ã äžèšã®æ¹æ³ã«ãããŠåºçºåæãšããŠçšããβâ
ïŒïŒ²ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã¯
次ã®æ§ã«ããŠè£œé ããã βâã¢ããã°ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã«346mg
ïŒ2.0ããªã¢ã«ïŒã®pH8.0ãªã³é žç·©è¡æ¶²ïŒml溶液ã«
è±ã®èèããåŸããããšã¹ãã©ãŒãŒïŒé µçŽ çªå·
EC3.1.1.1ïŒã·ã°ã瀟ãâ3128ïŒ2.89mgãå ã
ãã25âã§1.5æéãæã æ¹æããªããæŸçœ®ããã
åå¿æº¶æ¶²ã«0.1Nå¡©é žãå ãpHãçŽïŒã«èª¿ç¯ãã
20â以äžã§æ¿çž®ä¹Ÿåºãããçæç©ãã¡ã¿ããŒã«ã§
æœåºããæ¿çž®ãããšç²çæç©268mgãåŸãããã
ãã»ã«ããŒã¹ã«ã©ã ïŒã¯ãããã³ç€ŸCFâ11ïŒã§
åé¢ç²Ÿè£œãããšãæ²¹ç¶ã®Î²âïŒïŒ²ïŒâã¢ããã°ã«
ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«212mgãåŸãã IRïŒ3440ã1730ã2400ã2900cm-1ã NMRïŒD2OïŒïŒ2.59ïŒbdã2HãïŒ6HzïŒã2.84
ïŒbdã2HãïŒ6HzïŒ3.76ïŒïœã3HãCOOCH3ïŒã
3.85ã405ïŒïœã1HãCHïŒã ãαã22 DïŒ2.36ãïŒïœïŒ4.23ãH2OïŒ å®æœäŸ ïŒ ããªããšãã«ãã¹ãã€ã³157.4mgïŒ0.6ããªã¢
ã«ïŒãšãžããªãžã«ãžã¹ã«ãã€ã132.2mgïŒ0.6ããª
ã¢ã«ïŒãã¢ã»ããããªã«50mlã«æº¶ãããããã«Î²
âããšãã«âβâã¢ã©ãã³82.6mgïŒ0.5ããªã¢ã«ïŒ
ãå ããŠéæµäžæ¹æãã€ã€4.5æéåå¿ãããå
å¿åŸæžå§æ¿çž®ãæ®æž£ãã«ã©ã ã¯ãããã°ã©ãã€ãŒ
ïŒã·ãªã«ã²ã«40ïœããšãŒãã«âå¡©åã¡ãã¬ã³ïŒïŒ
ïŒã§æº¶åºïŒã«ãããã€ãã§ãã¬ãã©ãã€ãèå±€ã¯
ãããã°ã©ãã€ãŒïŒã·ãªã«ã²ã«ããšãŒãã«ããã³
ãŒã³ïŒïŒïŒã§å±éïŒã§ç²Ÿè£œããç®çã®ïŒâããšã
ã«âïŒâã¢ãŒããžãã³67.2mgïŒåç91ïŒ ïŒãåŸ
ãã IRïŒ3220ã1740ã1710cm-1ã NMRïŒ2.82ïŒdddãïŒïŒªïŒ14.9ã2.8ã0.9HzïŒã
1HãC3âïŒã3.40ïŒdddãïŒïŒªïŒ14.9ã5.2ã
2.3HzïŒã1HãC3âïŒã4.69ïŒddãïŒïŒªïŒ5.2ã
2.6HzïŒã1HãC4âïŒã6.66ïŒbrã1HãâïŒã
7.32ïŒïœã5HãC6H5ïŒã å®æœäŸ ïŒãïŒ åèšå®æœäŸïŒãïŒãšåæ§ã®æ¹æ³ã«æºããäžèšè¡š
ã«ç€ºãåºçºåæãäžèšè¡šã«ç€ºãæ¡ä»¶äžã«åå¿ã
ããäžèšè¡šã«ç€ºãçæç©ãäžèšè¡šã«ç€ºãåçã§åŸ
ãã
åè¿°ããåæçµè·¯ãçµãŠããšããã€ã·ã³ã補é ã
ãããã«æ®ã«æçšã§ããã 以äžãå®æœäŸãæ²ããŠæ¬çºæãããã«èª¬æã
ãã å®æœäŸ ïŒ Î²âïŒïŒ³ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹
ãã«165mgïŒ1.02ããªã¢ã«ïŒãã¢ã»ããããªã«20
mlã«æžæ¿ããããªããšãã«ãã¹ãã€ã³315mg
ïŒ1.20ããªã¢ã«ïŒãšããžããªãžã«ãžã¹ã«ãã€ã264
mgïŒ1.20ããªã¢ã«ïŒãšãå ããã®ã¡æ¹æãã€ã€12
æé55â60âã«å æž©ãããåå¿ãé²ãã«ã€ããŠæº¶
液ã¯é»è²ã«çè²ããŠããã åå¿åŸæº¶æ¶²ãæžå§æ¿çž®ããæ®æž£ãã·ãªã«ã²ã«40
ïœã®ã«ã©ã ã«è² è·ãããšãŒãã«âå¡©åã¡ãã¬ã³
ïŒïŒïŒïŒïŒã§æº¶åºãããç®çç©ãå«ããã©ã¯ã·ãš
ã³ãã·ãªã«ã²ã«20ïœã§åã³ã¯ãããã°ã©ãã€ãŒã«
ãããŠãç®çã®ïŒâïŒïŒ³ïŒâã¡ããã·ã«ã«ããã«
ã¡ãã«âïŒâã¢ãŒããžãã³123mgïŒåç84ïŒ ïŒã
çµæ¶ãšããŠåŸãã äžèšçæç©ã®èµ€å€åžåã¹ãã¯ãã«ãæ žç£æ°å ±é³Ž
ã¹ãã¯ãã«ããã¹ã¹ãã¯ãã«åã³æå 床ã¯æ¬¡ã®é
ãã§ããã IRïŒ3420ã1765ïŒÎ²âã©ã¯ã¿ã ïŒã1740cm-1ã NMRïŒ2.4ã2.9ïŒïœã3HãCH2COOCH3ãšC3â
ïŒã3.16ïŒdddïŒïŒªïŒïŒãïŒã15HzïŒã1HãC3â
ïŒ37.2ïŒïœã3HãCOOCH3ïŒã3.95ïŒïœã1HãC4
âïŒã6.15ïŒbrã1HãâïŒã ãαã25 DïŒ65.34ãïŒïœïŒ1.11ãCHCl3ïŒ M+ïŒïŒïŒ144 äžèšæ¹æ³ã«ãããŠåºçºåæãšããŠçšããβâ
ïŒïŒ³ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã¯
次ã®ããã«ããŠè£œé ããã ã€ïŒ βâã¢ããã°ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã« 4.68ïœïŒ26.7ããªã¢ã«ïŒã®ãžãªããµã³æº¶æ¶²ïŒ40
mlïŒã«ããã³ãžã«ãªãã·ã«ã«ããã«ã¯ããªã5.47
ïœïŒ32.1ããªã¢ã«ïŒã®ãžãªããµã³æº¶æ¶²ïŒ20mlïŒãš
ããªãšãã«ã¢ãã³3.25ïœïŒ32.1ããªã¢ã«ïŒã®ãžãª
ããµã³æº¶æ¶²ïŒ20mlïŒã滎äžãã宀枩ã§ïŒæéæ¹æ
ãããæåºããçµæ¶ãå¥ãã液ãæ¿çž®ãã·ãª
ã«ã²ã«ã«ã©ã ã¯ãããã°ã©ãã€ã§ç²Ÿè£œãããšãβ
âãã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°ã«ã¿ã«é žãž
ã¡ãã«ãšã¹ãã«7.41ïœïŒåç90ïŒ ïŒãæ²¹ç¶ç©ãšã
ãŠåŸãã ãïŒ Î²âãã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°
ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã«465mgïŒ1.5ããªã¢ã«ïŒ
ãã¢ã»ãã³1.5mlã«æº¶ãããpH8.0ãªã³é žç·©è¡æ¶²45
mlãå ãããè±ã®èèããåŸããããšã¹ãã©ãŒãŒ
ïŒé µçŽ çªå·ïŒEC3.1.1.1.ïŒã·ã°ã瀟ãâ3128ïŒã
èçœéãšããŠ2.7mgãå ãã25âã§ïŒæéãæã
æ¹æããªããæŸçœ®ããã2Nå¡©é ž2.5mlãå ãã溶
液ã®pHãçŽïŒã«èª¿ç¯ããå¡©åã¡ãã¬ã³ã§æœåºã
ããç¡æ°Žç¡«é žãããªãŠã ã§ä¹Ÿç¥åŸãæ¿çž®ãããšç²
çµæ¶419mgãåŸããã·ãªã«ã²ã«ã«ã©ã ã¯ãããã°
ã©ãã€ãŒã§ç²Ÿè£œãããšå åŠæŽ»æ§ã®Î²âïŒïŒ³ïŒâã
ã³ãžã«ãªãã·ã«ã«ããã«ã¢ããã°ã«ã¿ã«é žã¢ãã¡
ãã«ãšã¹ãã«410mgïŒåç93ïŒ ïŒãçµæ¶ãšããŠåŸ
ãã èç¹ïŒãšãŒãã«ããåçµæ¶ïŒïŒ97ã97.5âIR
ïŒKBrïŒïŒ3330ã2840ã2960ã1740ã1725ã1700
cm-1ã NMRïŒCDCl3ïŒïŒ2.69ïŒbdã4HãCH2ãïŒ
6HzïŒã3.65ïŒïœã3HãCO2CH3ïŒã4.17ã4.53ïŒïœã
1HãCHïŒã5.07ïŒïœã2HãCH2PhïŒã5.63ïŒbdã
1HãNHïŒã7.30ïŒïœã5HãPhïŒã ãαã25 DïŒ0.71ãïŒïœïŒ7.45ãCHCl3ïŒ ãã®Î²âïŒïŒ³ïŒâãã³ãžã«ãªãã·ã«ã«ããã«ã¢
ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«385mgïŒ1.3ã
ãªã¢ã«ïŒãã¡ã¿ããŒã«20mlã«æº¶ããã10ïŒ ãã©ãž
ãŠã âççŽ 40mgãå ããæ°ŽçŽ é°å²æ°äž30åæ¹æã
ããåå¿æº¶æ¶²ãéåŸæ¿çž®ãããšÎ²âïŒïŒ³ïŒâã¢
ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã®æ²¹ç¶ç©205
mgïŒåç98ïŒ ïŒãåŸããIRïŒ3440ã2400ã2900ã
1730cm-1ã NMRïŒD2OïŒïŒ2.59ïŒbdã2HãïŒ6HzïŒã2.84
ïŒbdã2HãïŒ6HzïŒã3.76ïŒïœã3HãCO2CH3ïŒã
3.85ã4.05ïŒïœã1HãCHïŒã ãαã25 Dâ5.52ãïŒïœïŒ3.26ãH2OïŒã å®æœäŸ ïŒ Î²âïŒïŒ²ïŒÎ²âã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãš
ã¹ãã«57mgïŒ0.35ããªã¢ã«ïŒãããªããšãã«ãã¹
ãã€ã³110mgïŒ0.42ããªã¢ã«ïŒããžããªãžã«ãžã¹ã«
ãã€ã93mgïŒ0.42ããªã¢ã«ïŒãã¢ã»ããããªã«ïŒ
mläžã«ãŠå®æœäŸïŒãšåæ§ã«åå¿ãè¡ãªããåå¿æ··
åç©ãã·ãªã«ã²ã«15ïœã®ã«ã©ã ã¯ãããã°ã©ãã€
ãŒã§ç²Ÿè£œãããšãç®çã®ïŒâïŒïŒ²ïŒâã¡ããã·ã«
ã«ããã«ã¡ãã«âïŒâã¢ãŒããžãã³37mgïŒåç73
ïŒ ïŒãåŸãã IRïŒ3420ã1765ïŒÎ²âã©ã¯ã¿ã ïŒã1740cm-1ã NMRïŒ2.4ã2.9ïŒïœã3HãCH2COOCH3ãšC3â
ïŒã3.16ïŒ1HãC3âïŒã3.72ïŒïœã3Hãâ
COOCH3ïŒã3.95ïŒïœã1HãC4âïŒã6.15ïŒbrã
1HãâïŒã ãαã25 Dâ26.03ãïŒïœïŒ1.26ãCHCl3ïŒM+ïŒïŒïŒ
144ã äžèšã®æ¹æ³ã«ãããŠåºçºåæãšããŠçšããβâ
ïŒïŒ²ïŒâã¢ããã°ã«ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«ã¯
次ã®æ§ã«ããŠè£œé ããã βâã¢ããã°ã«ã¿ã«é žãžã¡ãã«ãšã¹ãã«346mg
ïŒ2.0ããªã¢ã«ïŒã®pH8.0ãªã³é žç·©è¡æ¶²ïŒml溶液ã«
è±ã®èèããåŸããããšã¹ãã©ãŒãŒïŒé µçŽ çªå·
EC3.1.1.1ïŒã·ã°ã瀟ãâ3128ïŒ2.89mgãå ã
ãã25âã§1.5æéãæã æ¹æããªããæŸçœ®ããã
åå¿æº¶æ¶²ã«0.1Nå¡©é žãå ãpHãçŽïŒã«èª¿ç¯ãã
20â以äžã§æ¿çž®ä¹Ÿåºãããçæç©ãã¡ã¿ããŒã«ã§
æœåºããæ¿çž®ãããšç²çæç©268mgãåŸãããã
ãã»ã«ããŒã¹ã«ã©ã ïŒã¯ãããã³ç€ŸCFâ11ïŒã§
åé¢ç²Ÿè£œãããšãæ²¹ç¶ã®Î²âïŒïŒ²ïŒâã¢ããã°ã«
ã¿ã«é žã¢ãã¡ãã«ãšã¹ãã«212mgãåŸãã IRïŒ3440ã1730ã2400ã2900cm-1ã NMRïŒD2OïŒïŒ2.59ïŒbdã2HãïŒ6HzïŒã2.84
ïŒbdã2HãïŒ6HzïŒ3.76ïŒïœã3HãCOOCH3ïŒã
3.85ã405ïŒïœã1HãCHïŒã ãαã22 DïŒ2.36ãïŒïœïŒ4.23ãH2OïŒ å®æœäŸ ïŒ ããªããšãã«ãã¹ãã€ã³157.4mgïŒ0.6ããªã¢
ã«ïŒãšãžããªãžã«ãžã¹ã«ãã€ã132.2mgïŒ0.6ããª
ã¢ã«ïŒãã¢ã»ããããªã«50mlã«æº¶ãããããã«Î²
âããšãã«âβâã¢ã©ãã³82.6mgïŒ0.5ããªã¢ã«ïŒ
ãå ããŠéæµäžæ¹æãã€ã€4.5æéåå¿ãããå
å¿åŸæžå§æ¿çž®ãæ®æž£ãã«ã©ã ã¯ãããã°ã©ãã€ãŒ
ïŒã·ãªã«ã²ã«40ïœããšãŒãã«âå¡©åã¡ãã¬ã³ïŒïŒ
ïŒã§æº¶åºïŒã«ãããã€ãã§ãã¬ãã©ãã€ãèå±€ã¯
ãããã°ã©ãã€ãŒïŒã·ãªã«ã²ã«ããšãŒãã«ããã³
ãŒã³ïŒïŒïŒã§å±éïŒã§ç²Ÿè£œããç®çã®ïŒâããšã
ã«âïŒâã¢ãŒããžãã³67.2mgïŒåç91ïŒ ïŒãåŸ
ãã IRïŒ3220ã1740ã1710cm-1ã NMRïŒ2.82ïŒdddãïŒïŒªïŒ14.9ã2.8ã0.9HzïŒã
1HãC3âïŒã3.40ïŒdddãïŒïŒªïŒ14.9ã5.2ã
2.3HzïŒã1HãC3âïŒã4.69ïŒddãïŒïŒªïŒ5.2ã
2.6HzïŒã1HãC4âïŒã6.66ïŒbrã1HãâïŒã
7.32ïŒïœã5HãC6H5ïŒã å®æœäŸ ïŒãïŒ åèšå®æœäŸïŒãïŒãšåæ§ã®æ¹æ³ã«æºããäžèšè¡š
ã«ç€ºãåºçºåæãäžèšè¡šã«ç€ºãæ¡ä»¶äžã«åå¿ã
ããäžèšè¡šã«ç€ºãçæç©ãäžèšè¡šã«ç€ºãåçã§åŸ
ãã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ äžèšåŒ åŒäžãR1åã³R2ã¯ããããæ°ŽçŽ åååã¯ã¢ã
ãåºãè¡šãããR3åã³R4ã¯ããããæ°ŽçŽ ååã
ããšãã«åºåã¯äœçŽã¢ã«ã³ãã·ã«ã«ããã«ã¡ãã«
åºãè¡šãããR5ã¯æ°ŽçŽ åååã¯ãã³ãžã«åºãè¡š
ããã ã§è¡šããããβâã¢ããé žååç©ãã¢ã«ãã«ãã
ãªã«ã®ååšäžã«ããªããšãã«ãã¹ãã€ã³åã³äžèš
åŒ R6âââR6 ïŒïŒ åŒäžãR6ã¯ããªãžã«ããã³ãŸãã¢ãŸãªã«åã¯
ãã³ãºã€ãããŸãªã«åºãè¡šããã ã®è€çŽ ç°ãžã¹ã«ãã€ãååç©ã§åŠçããããšãç¹
城ãšããäžèšåŒ åŒäžãR1ãR2ãR3ãR4åã³R5ã¯åèšã®æå³ã
æããã ã§è¡šããããïŒâã¢ãŒããžãã³èªå°äœã®è£œé æ¹
æ³ã ïŒ è©²ã¢ã«ãã«ãããªã«ãã¢ã»ããããªã«ã§ãã
ç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ è©²åŠçãåžžæž©ä¹è³åå¿æ··åç©ã®æ²žç¹éã®æž©åºŠ
ã§è¡ãªãç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ è©²Î²âã¢ããé žååç©ãåå¿ç³»äž0.001ã1M
ã®æ¿åºŠã§çšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹
æ³ã
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55152151A JPS5777670A (en) | 1980-10-31 | 1980-10-31 | Preparation of 2-azetidinone derivative |
| AT81108875T ATE12104T1 (de) | 1980-10-31 | 1981-10-24 | Verfahren zur herstellung von 2-azetidinonderivaten. |
| EP81108875A EP0051234B1 (en) | 1980-10-31 | 1981-10-24 | A process for the production of a 2-azetidinone derivative |
| DE8181108875T DE3169283D1 (en) | 1980-10-31 | 1981-10-24 | A process for the production of a 2-azetidinone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55152151A JPS5777670A (en) | 1980-10-31 | 1980-10-31 | Preparation of 2-azetidinone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5777670A JPS5777670A (en) | 1982-05-15 |
| JPH0135823B2 true JPH0135823B2 (ja) | 1989-07-27 |
Family
ID=15534136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55152151A Granted JPS5777670A (en) | 1980-10-31 | 1980-10-31 | Preparation of 2-azetidinone derivative |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0051234B1 (ja) |
| JP (1) | JPS5777670A (ja) |
| AT (1) | ATE12104T1 (ja) |
| DE (1) | DE3169283D1 (ja) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5037974A (en) * | 1988-05-23 | 1991-08-06 | Merck & Co., Inc. | Cyclization process for synthesis of a beta-lactam carbapenem intermediate |
| EP0343716A1 (en) * | 1988-05-23 | 1989-11-29 | Merck & Co. Inc. | Process for synthesis of a beta-lactam carbapenem intermediate |
| JP2640986B2 (ja) * | 1990-11-08 | 1997-08-13 | é«ç éŠæå·¥æ¥æ ªåŒäŒç€Ÿ | ïŒïŒâ²ïœïŒïŒïœïŒâïŒâïŒïŒâ²âããããã·ãšãã«ïŒâã¢ãŒããžã³âïŒâãªã³åã¯ãã®èªå°äœã®è£œé æ³ |
| JP3726121B2 (ja) * | 2000-12-21 | 2005-12-14 | ç¬ç«è¡æ¿æ³äººç£æ¥æè¡ç·åç 究æ | βâã©ã¯ã¿ã ã®åææ¹æ³ |
| EP2163239A1 (de) | 2008-05-27 | 2010-03-17 | Qiagen GmbH | Produkte, die Biopartikel enthalten, Verfahren zu ihrer Herstellung |
| EP2264184A1 (de) | 2009-06-22 | 2010-12-22 | Qiagen GmbH | Verfahren zur Amplifikation von DNA unter Verwendung von Tetraethylenglykol, Kit-of-parts dafÃŒr und dessen Verwendung |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3119813A (en) * | 1960-05-10 | 1964-01-28 | Calanda Stiftung Instiftung Fu | Azetidine derivatives |
| JPS5265263A (en) * | 1975-10-06 | 1977-05-30 | Fujisawa Pharmaceut Co Ltd | Azetidinone compounds |
| US4174316A (en) * | 1978-08-14 | 1979-11-13 | Merck & Co., Inc. | 4-Iodomethylazetidin-2-one |
| JPS5573656A (en) * | 1978-11-30 | 1980-06-03 | Sankyo Co Ltd | 4-substituted azetidine-2-one compound and its preparation |
| JPS56142260A (en) * | 1980-04-09 | 1981-11-06 | Toyama Chem Co Ltd | 2-azetidinone and its preparation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4193917A (en) * | 1970-07-31 | 1980-03-18 | Glaxo Laboratories, Limited | Chemical compounds |
| JPS55133355A (en) * | 1979-04-03 | 1980-10-17 | Shionogi & Co Ltd | Inversion of 3-amino group of beta-lactam ring |
-
1980
- 1980-10-31 JP JP55152151A patent/JPS5777670A/ja active Granted
-
1981
- 1981-10-24 DE DE8181108875T patent/DE3169283D1/de not_active Expired
- 1981-10-24 EP EP81108875A patent/EP0051234B1/en not_active Expired
- 1981-10-24 AT AT81108875T patent/ATE12104T1/de not_active IP Right Cessation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3119813A (en) * | 1960-05-10 | 1964-01-28 | Calanda Stiftung Instiftung Fu | Azetidine derivatives |
| JPS5265263A (en) * | 1975-10-06 | 1977-05-30 | Fujisawa Pharmaceut Co Ltd | Azetidinone compounds |
| US4174316A (en) * | 1978-08-14 | 1979-11-13 | Merck & Co., Inc. | 4-Iodomethylazetidin-2-one |
| JPS5573656A (en) * | 1978-11-30 | 1980-06-03 | Sankyo Co Ltd | 4-substituted azetidine-2-one compound and its preparation |
| JPS56142260A (en) * | 1980-04-09 | 1981-11-06 | Toyama Chem Co Ltd | 2-azetidinone and its preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0051234B1 (en) | 1985-03-13 |
| EP0051234A1 (en) | 1982-05-12 |
| JPS5777670A (en) | 1982-05-15 |
| ATE12104T1 (de) | 1985-03-15 |
| DE3169283D1 (en) | 1985-04-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5306817A (en) | Process for the stereospecific synthesis of azetidinones | |
| EP0362902B1 (en) | Process and intermediates for beta-lactam antibiotics | |
| JP2640986B2 (ja) | ïŒïŒâ²ïœïŒïŒïœïŒâïŒâïŒïŒâ²âããããã·ãšãã«ïŒâã¢ãŒããžã³âïŒâãªã³åã¯ãã®èªå°äœã®è£œé æ³ | |
| JPH06732B2 (ja) | ïŒâã¢ã·ã«ã¢ããâïŒâïŒïŒâã¢ã«ã³ãã·âïŒâã¡ãã«ïŒãšããã·âïŒâã¢ãŒããžãã³é¡ | |
| US4633017A (en) | N-hydroxy protecting groups and process for the preparation of 3-acylamino-1-hydroxy-2-azetidinones | |
| EP0180252A1 (en) | Process of preparing azetidinone compounds | |
| FR2550533A1 (fr) | Procede pour la fabrication de derives de type penem | |
| EP0023097B1 (en) | De-arylmethylation of n-mono- or n-diarylmethyl-beta-lactams; novel azetizinones having anti-bacterial activity | |
| US5608102A (en) | Process for the preparation of β-phenylisoserine and its analogues | |
| US4584133A (en) | Process for the production of penems | |
| SU1442071A3 (ru) | СпПÑПб пПлÑÑеМО пÑПОзвПЎМÑÑ 4-аÑеÑПкÑО-3-ПкÑОÑÑОлазеÑОЎОМ-2-ПМа (егП ваÑОаМÑÑ) | |
| JP4142444B2 (ja) | ïŒâã¢ãŒããžãã³èªå°äœã®è£œé æ¹æ³ | |
| JPH0135823B2 (ja) | ||
| KR910004090B1 (ko) | β-ëœí íí©ë¬Œì ì ì¡°ë°©ë² | |
| US4487963A (en) | Enantioselective synthesis of 4-amino-3-hydroxy-2,4-(disubstituted)pentanoic acid | |
| US4506085A (en) | β-Aminoacid derivatives and process for production thereof | |
| EP0083039B1 (en) | 4-cyano-2-azetidinones and production thereof | |
| US4539148A (en) | Production of 1-oxacephams and intermediates | |
| KR910005230B1 (ko) | ìì í°ëë Œì ì ì¡°ë°©ë² | |
| EP0096496B1 (en) | Preparation of penicillin and cephalosporin compounds and novel intermediates useful therein | |
| EP0081817B1 (en) | Optically-active diamide derivatives | |
| EP0209886B1 (en) | Beta-n-substituted aminothiol ester and process for preparing the same | |
| JPS6363655A (ja) | å åŠæŽ»æ§Î²âã©ã¯ã¿ã ã®è£œé æ¹æ³ | |
| EP0064797B1 (en) | N-diarylmethyl-3-amino-4-alkenaryl-2-azetidinones and their preparation | |
| US4461726A (en) | Desulfurization of penicillins to prepare azetidinones |