JPS6143353B2 - - Google Patents
Info
- Publication number
- JPS6143353B2 JPS6143353B2 JP52017992A JP1799277A JPS6143353B2 JP S6143353 B2 JPS6143353 B2 JP S6143353B2 JP 52017992 A JP52017992 A JP 52017992A JP 1799277 A JP1799277 A JP 1799277A JP S6143353 B2 JPS6143353 B2 JP S6143353B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- general formula
- compound
- hydrogen
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 87
- 238000006243 chemical reaction Methods 0.000 claims description 34
- -1 lactone diol Chemical class 0.000 claims description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 150000002596 lactones Chemical class 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 150000002009 diols Chemical class 0.000 claims description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 3
- 239000008098 formaldehyde solution Substances 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 5
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 4
- 230000002378 acidificating effect Effects 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- 239000000047 product Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 10
- 238000010478 Prins reaction Methods 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 150000003180 prostaglandins Chemical class 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 229930040373 Paraformaldehyde Natural products 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 230000000704 physical effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
- 229910000831 Steel Inorganic materials 0.000 description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
- 230000021736 acetylation Effects 0.000 description 4
- 238000006640 acetylation reaction Methods 0.000 description 4
- 238000006136 alcoholysis reaction Methods 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000010959 steel Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000003377 acid catalyst Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229940127293 prostanoid Drugs 0.000 description 3
- 150000003814 prostanoids Chemical class 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical group C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- 150000000093 1,3-dioxanes Chemical class 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 230000006196 deacetylation Effects 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KFUSEUYYWQURPO-UHFFFAOYSA-N 1,2-dichloroethene Chemical group ClC=CCl KFUSEUYYWQURPO-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- SZTBMYHIYNGYIA-UHFFFAOYSA-N 2-chloroacrylic acid Chemical compound OC(=O)C(Cl)=C SZTBMYHIYNGYIA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZETHHMPKDUSZQQ-UHFFFAOYSA-N Betulafolienepentol Natural products C1C=C(C)CCC(C(C)CCC=C(C)C)C2C(OC)OC(OC)C2=C1 ZETHHMPKDUSZQQ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- PCSMJKASWLYICJ-UHFFFAOYSA-N Succinic aldehyde Chemical compound O=CCCC=O PCSMJKASWLYICJ-UHFFFAOYSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000004808 allyl alcohols Chemical group 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- WRZSGVPZDAZRSM-UHFFFAOYSA-N bicyclo[2.2.1]hept-4-en-3-one Chemical class C1C=C2C(=O)CC1C2 WRZSGVPZDAZRSM-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000422 delta-lactone group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000012691 depolymerization reaction Methods 0.000 description 1
- HEOKFDGOFROELJ-UHFFFAOYSA-N diacetal Natural products COc1ccc(C=C/c2cc(O)cc(OC3OC(COC(=O)c4cc(O)c(O)c(O)c4)C(O)C(O)C3O)c2)cc1O HEOKFDGOFROELJ-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- TUHMQDODLHWPCC-UHFFFAOYSA-N formyl cyanide Chemical compound O=CC#N TUHMQDODLHWPCC-UHFFFAOYSA-N 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003476 thallium compounds Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
ãçºæã®è©³çŽ°ãªèª¬æã
æ¬é¡çºæã¯å
åŠæŽ»æ§ãŸãã¯ã©ã»ãäœã®ã©ã¯ã
ã³ã»ãžãªãŒã«èªå°äœã«é¢ããããã®ãããªååç©
ã¯ã³ãŒã¬ã€ïŒCoreyïŒã®ããã¹ã¿ã°ã©ã³ãžã³åæ
ã«ãããäžéäœãšããŠæçšã§ãããæ¬é¡çºæã¯ãŸ
ããããååç©ã®èª¿è£œæ¹æ³ã«ãé¢ããã 倩ç¶ããã¹ã¿ã°ã©ãžã³ã¯å å çµèãã«ã¢ã³ã®é¡
èãªçç©åŠç掻æ§ãæãã矀ãæ§æããã倩ç¶ã
ãã¹ã¿ã°ã©ã³ãžã³ãåé¢ããããã€ãããã®æ§é
ã調ã¹ããã1960幎ããå§ãŸãã巚倧ãµã€ãºã®ç
究äœæ¥ãããããååç©ãåæããæ¹æ³ã確ç«ã
ãããšãšãŸãé¡äŒŒæ§é ã®ååç©äžããããããã¹
ã¿ãã€ãâãããããã®è¬åŠç掻æ§ãè©äŸ¡ãã
ãJ.A.C.S.ïŒ93ïŒ4326ïŒ1971ïŒãããã«èª¿è£œããã
ãšãé²ããããŠãããããã¹ã¿ã°ã©ã³ãžã³ã®åœå
ãšççåŠç掻æ§ããã³ãããã®åææ¹æ³ã¯ãå€æ°
ã®è«æãã®ä»ã®åè¡ç©ïŒããšãã°ãArzneimittel
Forseh.25ïŒ135ïŒ1975ïŒïŒã«ãŠæãã«ãããŠã
ãã ç«äœååŠçåé¡ãéçšæ§ããã³éèŠæ§ã®è§£æ±ºã«
é¢ããŠã¯ãJ.A.C.S.ïŒ91 5675ïŒ1969ïŒïŒä»äž
èªã92ïŒ397ïŒ1970ïŒãããã³ä»äžè©Š93ïŒ1490
ïŒ1971ïŒã«èšèŒã®åæããçš®ã ã®å šåææ³ã®äžã§
ãé¡èãªå°äœãå ãããã€ãŸãå·¥æ¥åèŠä»¶ããå
足ããããã®åæã®æçµè£œåã¯PGF2ãã§ããã
ããã¯ä»ã®è¬çåŠçã«éèŠãªå€©ç¶ããã¹ã¿ã°ã©ã³
ãžã³ãããªãã¡PGF1ïŒPGF2ïŒPGF1ãããŸãã¯
PGF1ãã«å€æããããšãã§ããã äžèšåæäžããŠã€ãããïŒWittigïŒåå¿ãäºé
çµåã®ç«äœéžæç圢æçšã«äœ¿çšãããããŠã€ãã
ãåå¿ãå©çšãããã®ã¯ãã¢ãªã«ã¢ã«ã³ãŒã«éšå
ãå«ãåŽéäžã«å¿ èŠãªãã¹ãããŒãïŒå®å®åãã
ã€ãªãïŒãšãã©ã³ã¹åäºéçµåã圢æãããåæ
ã«ä»ã®åŽéäžã«ïŒâã«ã«ããã·ããã«ããªããšã
ã«ãã¹ãããŠã ãããã€ãïŒæŽ»æ§ã€ãªãïŒããçº
çãããã¹ãã©ã³ãšã·ã¹åäºéçµåã圢æãããª
ããã°ãªããªããšããããã¹ã¿ã°ã©ã³ãžã³ç¹æã®
ååŠæ§é ã«èµ·å ããå¿ èŠæ§ããã§ããã ãã®åæã®åºæ¬äžéäœã¯ãPGF2ãå ã«ããã
ããã«ãåäžã®çµ¶å¯Ÿçããã³çžå¯Ÿçé åã«å¯ŸããŠ
äžæã®ïŒã€ã®äžå¿ãæãããããããâCoreyã¢
ã«ãããâã§ããããã®åææ³ã«ããã°ãåŒã®
ã¢ã«ããã ã¯ã次ã®ç¥å³ã«ç€ºãããããã«ã åŒã®ã¢ã«ã³ãŒã«ãé žåããããšã«ãã€ãŠèª¿è£œã
ããã äžè¬åŒã®ã¢ã«ã³ãŒã«èª¿è£œçšã®ç«äœååŠçå¶åŸ¡
åå¿ã¯æ¬¡ã®ç¥å³ã«ç€ºãããŠããïŒ ãã®åæã®éåžžã«å€æ°ã®æ¹è¯å€æŽã¯ãçš®ã ã®å
è¡ç©ãç¹èš±ã§å ¬åãããŠããããããšãã°J.C.S.
Chem.Comm.151ïŒ1974ïŒïŒåè©Š642ïŒ1974ïŒïŒ
åè©Š39ïŒ1975ïŒïŒJ.A.C.S.96ïŒ5261ïŒ1974ïŒãã ããããªããããããã®å€æŽã¯ã©ãããäžè¬åŒ
ã®ãããµãããâïŒ(H)âã·ã¯ããã³ã¿ããïœã
ãã©ã³èªå°äœã®é©åœãªç«äœç°æ§äœã6aïŒïŒ³ïŒïŒ3a
ïŒïŒ²ïŒïŒïŒïŒïŒ³ïŒïŒïŒïŒïŒ²ïŒãã圢æãããçºã«å¿ èŠ
ãªäžé£ã®åå¿å·¥çšã»å€æŽãããã®ã§ã¯ãªãããã
ããå Žåã次ã®åå¿ã次ã®é åºã§çšããããïŒç«
äœçã«å¶åŸ¡ããããã€ã«ã¹ãŒã¢ã«ããŒïŒDiels
AlderïŒåå¿ã«ãã€ãŠèª¿è£œããããã·ã¯ããïŒïŒ
ïŒïŒïŒããããã³âãªã³èªå°äœã¯ãé åèŠåæ§ã®
ãã€ã€ãŒâããªã³ã¬ãŒïŒBaeyerâVillingerïŒé ž
åãããããããÎŽâã©ã¯ãã³ã¯ããããªãã·é ž
ãŸã§å æ°Žå解ããããããããšãŒãâã©ã¯ãã³åœ¢
æåå¿ããããããšãäžè¬åŒã®äžèšååç©ãã
ãããã ããããªããããã€ãŒãïŒã«è¿°ã¹ãåæã¯äžå©
ãªç¹ãå€ãããã®æ¹æ³ã§äžè¬åŒã®ååç©ã調補
ããããšã¯ãåå¿æ®µéæ°ãå€ãããã€è©Šè¬ãåŸã«
ãããïŒããšãã°ãαâã¯ããã¢ã¯ãªã«é žãšã¯ã
ãã¡ãã«ã»ãã³ãžã«ãšã¹ãã«ã¯ãã€ãšå€æ°ã®åå¿
段éãæããåæã«ãŠèª¿è£œããããïŒãŸãæ¯æ§ã
ããïŒããšãã°ãã¿ãªãŠã ååç©ãããªãããã³
æ°ŽçŽ åç©ïŒãšããäºå®ã«åºã¥ãã極端ã«è€éã§ã
ã€çµè²»ããããã ã³ãŒã¬ã€åæäžã®äžè¬åŒã®ååç©ã眮ãæã
ããåŒã®äžéäœã¯ããã€ãŒãïŒã«ç€ºãæ¹æ³ãJ.
A.C.S.ïŒ95ïŒ6853ïŒ1973ïŒãã«ãã€ãŠèª¿è£œããã
ãšãã§ããã ããããªããããã®åæã¯ãŸãå€æ°ã®åå¿æ®µé
ãããªãããã€ãšããã·åã«ãã€ãŠããããç°æ§
äœã¯ã¯ãããã°ã©ãã®ã«ã©ã ã§åé¢ããªããã°ãª
ããããã®ããã«ãã®æ¹æ³ã¯è€éã§ããã€çµè²»ã®
ããããã®ã§ããããšããããã æ¬çºæè ã¯é©ãã¹ãããšã«ãäžè¬åŒ ãåŒäžãR3ãšR4ã¯åçš®ãŸãã¯ç°çš®ã§ãããã
ã€æ°ŽçŽ ã§ãããããŸãã¯ä»»æã«ïŒåãïŒåãŸãã¯
ïŒåã®ããã²ã³ã«ãã€ãŠçœ®æãããŠããŠãããäœ
çŽã¢ã«ã«ãã€ã«åºã瀺ãããã€R3ãšR4ãšã¯å ±ã«
éåããŠR5ââR6åºã圢æããŠãããR5ãšR6
ã¯æ°ŽçŽ ãã¡ãã«åºããã³ããšãã«åºããéžæã
ããR5ããã³R6ã®ããããäžã€ãããšãã«åºã§
ããå Žåã«ã¯ä»ã®äžã€ã¯æ°ŽçŽ ã瀺ãã ã«ãŠç€ºãããååç©ïŒåŸèšã®åŒã«è©²åœïŒããæ¬
é¡çºæã®æ¹æ³ã«ããã°ãã¯ããã«åçŽãªæäœã§å
æããããšãã§ããããšãèŠåºããã æ¬é¡çºæã¯ãããªã³ã¹ïŒPrinsïŒåå¿ãç«äœèŠ
å¶çãã©ã³ã¹âä»å ç¹æ§ãæãããChem.ReWs.
51ïŒ505ïŒ1952ïŒãããšãå©çšãããã®ã§ãããé ž
觊åªã®ååšäžã§ãã«ã ã¢ã«ãããããªã¬ãã€ã³ã«
ä»å åå¿ããããªã³ã¹åå¿ã®ç«äœååŠãšåå¿æ©æ§
ã¯ããã§ã«åºãè©äŸ¡ãããŠããããBull.Chem.
Soc.Chem.FranceïŒ357ïŒ1952ïŒã ããªã³ã¹åå¿ã¯å¿ ãããé åèŠå¶çã§ãªããšã
ãŠããäžè¬ã«ç«äœèŠå¶çã«é²è¡ãããåå¿åªäœäž
ã®é žã¯äºéã®åœ¹å²ããªããšããïŒé žã¯åäœããªã«
ã ã¢ã«ããããšåå¿ãã第ïŒåå¿æ®µéã§äºéçµå
ã®Ïâé»åç³»ãæ»æããã¡ãããŒã«ã«ããªã³ïŒïŒ
CH2OHïŒãã€ããããã€ä»æ¹ããªã«ã ã¢ã«ãã
ãéåäœïŒãã©ããªã«ã ã¢ã«ããããããªãªãã·
ã¡ãã¬ã³ïŒã®è§£éååå¿ã«ããã觊åªãšããŠäœçš
ãããé žãšããŠã¯ããšãã°ãç¡«é žããªã³é žãäžã
ãåããŠçŽ âãšãŒãã«åç©ãªã©ãçšããããã ããªã³ã¹åå¿ã®æçµçæç©ã¯ã䜿çšãã溶å€
ïŒé ¢é žãæ°Žãéãããã³æ§æº¶å€ïŒã«å€§ããäŸåã
ããäžè¬ã«çšããããé ¢é žã氎溶å€äžã§ã¯ãäž»ç
æç©ã¯ã䜿çšãªã¬ãã€ã³ããèªå°ããããããã
ã·ã«âã¡ãã«ã¢ã«ã³ãŒã«ãšããã®ã¢ã»ãã«åç©ã
ãã³ïŒïŒïŒâãžãªããµã³èªå°äœã§ããã æ¬é¡çºæã®æ¹æ³ã«ãããŠãåŒã®å ¬ç¥ã®ïŒïŒ
3aïŒïŒïŒ6aâããã©ãããâ2Hâã·ã¯ããã³ã¿
ããïœããã©ã³âïŒâãªã³ ïŒãã®ååç©ã®ä»ã®éçšåïŒã·ã¹âïŒâãªããµ
âãã·ã¯ããïŒïŒïŒïŒïŒããªã¯ãâïŒâãšã³âïŒ
âãªã³ïŒãšãã®å åŠæŽ»æ§ã®åœ¢æ ãåŒã®ïŒâïŒã
ãã³ïŒïŒïŒååç©ã§ããïŒâïŒâã6aïŒïŒ³ïŒïŒ3a
ïŒïŒ²ïŒãâããã³ïŒïŒïŒâã6aïŒïŒ²ïŒïŒ3aïŒïŒ³ïŒãâ
ç°æ§äœããããªã³ã¹åå¿ãè¡ãªãå Žåã®ãªã¬ãã€
ã³ãšããŠäœ¿çšããããäžèšååç©ã¯TeTr.
Lett.307â310ïŒïŒ1970ïŒã«å®äŸãšããŠæ瀺ãããŠ
ããã åŒã®ååç©ã¯ã·ã¯ããã³ã¿ãžãšã³ã«ã¢ããŒãŸ
ãã¯ãžâã¯ãã«ãšãã¬ã³ãä»å ãããããŸãã¯åŒ
ã®å ¬ç¥ã®ïŒïŒïŒïŒïŒïŒïŒãããâïŒâãšã³âïŒ
âãªã³ ãéé žåæ°ŽçŽ ã«ãã€ãŠé žåããããšã«ããïŒåå¿
段éã§èª¿è£œã§ãããïŒïŒïŒâαâã¡ãã«âãã³ãž
ã«ã¢ãã³ã«ããåŒã®ååç©ã®åå²ã¯ãæç®ã«èš
è¿°ãããŠãããïŒJ.A.C.S.ïŒ95ïŒ6832ïŒ1973ïŒïŒã
åŒã®ååç©ã®å·Šå³åã®èª¿è£œã®ããã«ã¯ãïŒæ®µé
ãããªãäžæåæãJ.A.C.S.ïŒ95ïŒ7171ïŒ
1973ïŒïŒã«èšèŒãããŠãããåŒã®ååç©ã¯ãã®
ã©ã»ã圢ã§ããå åŠæŽ»æ§ïŒïŒïŒããã³ïŒâïŒåœ¢ã§
ãã åæ§ã«çš®ã ã®ããã¹ã¿ãã€ããããã¹ã¿ãã€ãäž
éäœã®åæã«ãããŠé¡èã«æ±ºå®ç圹å²ãæŒããŠã
ãããTetr.Lett.4753ïŒ1971ïŒïŒåè©Š3091
ïŒ1973ïŒïŒJ.A.C.S.ïŒ95ïŒ6832ïŒ1973ïŒïŒTetr.
Lett.2439ïŒ1974ïŒãäžèšååç©ã倩ç¶ã®ããã¹ã¿
ã°ã©ã³ãžã³ã«å€æããããã«ã¯ãããããªããã
ãã éåžžã«æ£ç¢ºãã€è€éãªåå¿æ¡ä»¶ã§ã®ã¿èª¿è£œã
ãããã€é«åºŠã®ããã€ãã®é£ç¶ã¯ãããã°ã©ã粟
補ã®äžã§ã€ãããããªããŠã ã»ãžã¢ã«ã±ãã«ã»ã
ãŠãã¬ãŒããŸãã¯æ··åããŠãã¬ãŒãã®å ±åœ¹ä»å ã«
åºã¥ãè€éãªåå¿ãèšèŒãããŠããã ãã§ããã æ¬é¡çºæã®çµæãšããŠãç¡«é žè§Šåªã®ååšäžã§ã®
åŒã®ã©ã»ãäœãŸãã¯å åŠæŽ»æ§ååç©ã®åå¿ïŒã
ãªã³ã¹åå¿ïŒã¯ãé ¢é žåªäœäžã§å®æœãããå Žåã
é åèŠå¶çã§ããããã€äž»çæç©ãšããŠåŒïœã®
ååç© ãããããåéã§ããããäžæ¹åŒïœ ã¯åå¿æ¡ä»¶ã«ããïŒã10ïŒ ã®éã«ãããããã
ãŠãåŒïœããã³ïœã®éšåçã«ã¢ã»ãã«åãã
ãååç©ã®åœ¢æã¯ã枩床ãé©çšããããã«ã ã¢ã«
ãããããã©ããªã«ã ã¢ã«ãããããã³ããªãªã
ã·ã¡ãã¬ã³ã®å質ããã³é ¢é žæº¶åªã®æ°Žå«æéã®é¢
æ°ã§ããããããã®éšåã¢ã»ãã«åç©ãé€å»ãã
ã«ã¯ãããããå«ãåå¿çæç©ããã®ãŸãŸäŸãã°
ç¡æ°Žé ¢é žã«ãã€ãŠã¢ã»ãã«åãã以å€ã«æ¹æ³ããª
ãã ããªã³ã¹åå¿æ©æ§ã®çµæãåŒïœã§ç€ºãããå
åç©ã¯ãããã³è§Šåªåå¿ã«ããã¢ã·ã«åºç§»ååå¿
ã«ææã§ããããã«åŒïœã§ç€ºãããååç©ãç
æãããéšåã¢ã»ãã«åã©ã¯ãã³ãžãªã«ã®äž¡è
ã¯ããããã³äŸèäœè§Šåªã®ååšã§ã¢ã»ãã«åã§ã
ããããããããšã¹ãã«åäžã«åœ¢æããæ°Žã¯ç³»å
ã«æ®ããããããŠå¹³è¡¡æ··åç©ãåå¿æ¡ä»¶ã§ããŸã
çµæç©ãšããŠããããã åŒïœãšïœã®ååç©ã®ã¢ã»ãã«åé床ã¯é¡è
ã«ç°ãªããæåŸ ãããããã«ãïŒçŽããããã·åº
ã¯ïŒçŽããããã·ã«ããæ°åã®é床ã§ã¢ã»ãã«å
ããããïŒçŽããïŒçŽæ¹åãžã®ã¢ã·ã«åºç§»åé床
ã¯ããã®åå¿æ¹åãžã®ç§»åé床ããã倧ããã éšåã¢ã»ãã«åçæç©ã®åœ¢æã¯ãã¢ã»ãã«åç
æç©ãã¢ã«ã«ãªã¢ã«ã³ãã·ããã¢ã«ã«ãªçé žå¡©ã
ãŸãã¯é žã«ããæ¥è§Šçå æ°Žå解ãŸãã¯ã¢ã«ã³ãŒãª
ã·ã¹ãããããšãããªããã®äžå©çããªããã¢ã«
ã³ãŒãªã·ã¹ã¯ã倧äœ10ã20ã¢ã«ïŒ ã®é žè§Šåªã®ååš
äžã§éè¡ãããããé žã«ããæ¥è§Šã¢ã«ã³ãŒãªã·ã¹
ã¯ãé±é žãŸãã¯ã¢ãªãŒã«ã¹ã«ãã³é žè§Šåªã®ååšäž
ã§çæããé ¢é žã¢ã«ãã«ãèžçããããšã«ãã€ãŠ
è¡ãªãããšãã§ãããã¢ã«ã³ãŒãªã·ã¹ã¯ãããã
ãé ¢é žã¡ãã«ã䟿å©ãªäœæ²žç¹ãæãããã€ããã
ãŠå®¹æã«èžçºããããšãã§ããããã奜ãã§ã¡ã¿
ããŒã«ã«ãã€ãŠå®æœããããããªã³ã¹åå¿ã«ãã€
ãŠããããçæç©æ··åç©ã¯é žãŸãã¯ã¢ã«ã«ãªæ§å
æ°Žå解ã«ãããåŒã®ã©ã¯ãã³ãžãªãŒã«ã調補ã
ããã åŒã®ååç©ã¯å ¬ç¥ã§ãããïŒJ.A.C.S.ïŒ93ïŒ
1491ïŒ1971ïŒïŒãã®åŒçšæç®äžã«ããã®ååç©ã®
ä»ã®èª¿è£œæ³ããã®èç¹ããã³æå 床ãèšèŒãããŠ
ãããæ¬é¡çºæã®æ¹æ³ã«ãã調補ãããåŒã®å
åç©ã®ç©çç¹æ§ã¯æç®äžã«çºè¡šããããã®ãšåç
ã§ããã åŒã®å åŠæŽ»æ§ååç©ãé žè§Šåªã«ããã¡ã¿ããŒ
ãªã·ã«ã«ãã€ãŠèª¿è£œãããå Žåã溶å€èžçºåŸãæ®
åããçµæ¶æ§ç²çæç©ã®éžæçã¢ã»ãã«åã«ãã€
ãŠåŒã®ååç©ã«ïŒãã³ã¬ãªãŒç¹èš±CIâ1652ïŒã
ãŸãéžæçé žåã«ããããã以äžã®ãªããã®ç²Ÿè£œ
ãè¡ãªãããšãªãã«ãåŒã®ååç©ãšããããšã
ã§ããã ã¢ã«ã«ãªã¢ã«ã³ãã·ããŸãã¯ã¢ã«ã«ãªçé žå¡©ã«
ããæ¥è§Šã¢ã«ã³ãŒã·ã¹ã¯åžžæž©ã§éè¡ã§ããããã
ãããã®å Žåã溶å€èžçºåã®äžåãããšãã°ã·ãª
ã«ã²ã«ã«ã©ã ããã®æ··åç©ãééãããããšã«ã
ããçããå¡©é¡ãé€å»ããã«ã¯å¥œéœåã§ããã åŒã®ååç©ã¯ãé ¢é žãšãã«ãé ¢é žãšãã«ïŒã
ããµã³ãŸãã¯ã¢ã»ããããªã«ãšãŒãã«ããåçµæ¶
ã§ãããåçµæ¶åŸãåŒã®ååç©ã¯80ã90ïŒ ã®å
éã§ãããããïŒåŒã®åºçºç©è³ªã«åºããŠèšç®ïŒ ããªã³ã¹åå¿ã«ãã€ãŠããããäž»çæç©æ··åç©
ã¯ããã®ãŸãŸã®ã¢ã»ãã«åã«ãããã»ãšãã©å®é
çã«åŒïœã®ã©ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒãã«å€
æã§ãããããããŠãæ°ååç©ã§ããåŒïœã®å
åç©ã¯ãåŒã®ååç©ããåºçºããå Žåã90ã95
ïŒ ã®åéã§ããããã ããªã³ã¹åå¿ã«ãŠèª¿è£œãããåŒïœã®ååç©ã®
絶察çããã³çžå¯Ÿçé åã蚌æããããã«ãçºæ
è ã¯ãŸããã€ãŒãïŒã«ç¥ç€ºããåå¿ã«åŸã€ãŠãã®
ååç©ãã€ãã€ãã ã³ãŒã¬ã€åæã«ãŠå ¬ç¥ã®åŒã®ãšãŒãã©ã¯ãã³
ããåºçºãããã®ååç©ã«æã®åœ¢ããªãäžå¿éšã«
ã¯é¢ä¿ã®ãªãïŒé£ã®å€æåå¿ãè¡ãªã€ãããã®æ
å æ§ãæããããããŠããããååç©ã¯ãããªã³
ã¹åå¿ã«ããåŒã®ïŒâïŒååç©ããã€ãããã
åŒIcã®å·Šæå ååç©ãšåäžã§ãã€ãã åŒïœã®ååç©ã¯ãåŒïœã®ã©ã¯ãã³ãžãªãŒã«
ãžã¢ã»ããŒãã®éšåè±ã¢ã»ãã«åã«ãã€ãŠèª¿è£œã
ããããã®åŒïœã®ååç©ã¯åŒã®ååç©ãšåæ§
ã®æ¹æ³ã§ã³ãŒã¬ã€åæã«äœ¿çšãåºæ¥ãããã®è±ã¢
ã»ãã«åã¯äžè¿°ã®ã¢ã·ã«åºç§»åã«åºã¥ãã絶察ç
ã«éžæçãªãã®ã§ã¯ãªããããããªããããã®å
å¿æ··åç©äžã®åŒïœãšïœã®ååç©ã®éã¯ãæé©
ã®ãããã³éãã¢ã«ã³ãã·ããšçé žå¡©ã®æ¿åºŠãå
å¿æéåã³ããªã«ããããåå¿æž©åºŠãã¿ãã ãã
ãšã«ãã€ãŠæ¥µå°åã§ãããéšåã¢ã»ãã«ååŸãåŒ
ïœã®ååç©ã¯ã«ã©ã ã¬ã¹ã¯ãããã°ã©ãã€ã«ã
ããåŒïœãšïœã®ååç©ããåé¢ã§ããããã®
åé¢ã¯ã溶é¢å€ãšããŠã¡ã¿ããŒã«æ¿åºŠãå¢å ããŠ
è¡ãé ¢é žãšãã«ïŒãšã¿ããŒã«ãçšããåŸé 溶é¢æ³
ã«ããã·ãªã«ã²ã«ã«ã©ã äžã§è¡ãªãããããŸãã
第ïŒçåã¯åŒïœã®ååç©ãå«ã¿ãç¶ããŠåŒïœ
ã®ååç©ããããŠããããåŒïœã®ååç©ããã
ããã å°éã®ãªã³ãªãã·ã¯ãã©ã€ã觊åªã®ååšã§ãå¯
éç³»å ã§å®€æž©ã«ãŠæ°æ¥éãåŒïœã®ããããã©ã¯
ãã³ãžãªãŒã«ããã³ãŒã³å ã§éå°éã®ãã©ãã«ã
ã¢ã«ããããšåå¿ãããå ŽåãR5ãšR6ãæ°ŽçŽ ã§
ããäžè¬åŒïœã®ïŒïŒïŒâãžãªããµã³èªå°äœ ãããããããã®çæç©ã®æ ¹è·¡éã¯ããŸãããªã³
ã¹åå¿ã®çæç©äžã«æ€åºã§ãããç°ç¶ã¢ã»ã¿ãŒã«
ã®åœ¢æã«å°ãäžèšãããŸãã®åå¿ã¯ããŸãä»ã®ã¢
ã«ããããã±ãã³ã«ãã€ãŠãéè¡ããããããã
ãŠããã«ã ã¢ã«ãããããã³ãºã¢ã«ããããŸãã¯
ã¢ã»ãã³ã«çœ®ãæããå Žåãé¡èã«ãR5ãããš
ãã«åºã§ããã€R6ãæ°ŽçŽ ã§ãããããŸãã¯R5ãš
R6ãåã ã¡ãã«åºãè¡šããäžè¬åŒïœã®ååç©
ããããããäžè¬åŒïœã®ããããŠããããåå
ç©ã¯ä¿è·ããã圢ã®åŒïœã®ååç©ã®ïŒåã®ãã
ããã·ã«åºãå«ãæçšãªäžéäœã§ãããä¿è·ãã
ãç°ç¶ã¢ã»ã¿ãŒã«ã¯ãããããªããããã ãããª
é žåªäœäžã§å®¹æã«æ¶å»ã§ããã åŒã®ååç©ã«å¯ŸããŠå®éãããããªã³ã¹åå¿
ã«ãããŠãé ¢é žã¯ä»ã®äœçŽã¢ã«ã«ã³ã«ã«ããã·ã«
é žã«çœ®æãããããŸããïŒåãïŒåãŸãã¯ïŒåã®
ããã²ã³ãå«ãäœçŽã¢ã«ã«ã³ã«ã«ããã·ã«é žã«ã
ã€ãŠåå¿ãè¡ãªããããšããR3ãšR4ãšã¯æ°ŽçŽ ã
ãã³ïŒãŸãã¯é©åœãªã¢ã·ã«åºãè¡šããäžè¬åŒã®
ååç©ãããããã ãã®åå¿ã¯ãŸãé žããªããšãéè¡ãããããã®
å Žåãæ¿ç¡«é žè§ŠåªãšããããåŒã®ååç©ããã
ã«ã ã¢ã«ããã氎溶液äžã«å ããããã å¯éç³»ã¯70âã«ãŠã70ã80æéãããããä¿æ
ããããäž»çæç©ã¯åŒïœã®ååç©ã§ãããã
R5ãšR6ãæ°ŽçŽ ã§ããåŒïœã®ååç©ããŸãå°é
ãããããåŒïœã®ååç©ã¯æ··åç©ããã¯ããã
ã°ã©ãã€ã«ãã€ãŠåé¢ããããã次ã®å®æœäŸã¯å
ãªãåŒäŸã«ãããããªãã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒ6aβâããã©ãããâ
2Hâã·ã¯ããã³ãããïœããã©ã³âïŒâãªã³
ã«ãã«ã ã¢ã«ãããã®ä»å å°å ¥ã§ããã¬ã©ã¹ç®¡ãŸãã¯ã¬ã©ã¹æ ãåããã
ã©ã¹ã³å ã«ãŠã2.1ïœã®ãã©ãã«ã ã¢ã«ããã
ïŒããªãªãã·ã¡ãã¬ã³ïŒã15mlã®æ°·é ¢é žäžã«æžæ¿
ãããïŒïœã®æ¿ç¡«é žã宀枩ã«ãŠããã¯ãããªãã
滎äžããããçãããã¯ãåŸããã«ã ã¢ã«ããã
éåäœã®50ã70ïŒ ã¯æº¶è§£ãããïŒè§£éåã¯ãã®æ··
åç©ã50ã60âã«30ã40åä¿æãããšå®çµã§ã
ããïŒãã®åŸã18mlã®æ°·é ¢é žäžã«2.3ïœïŒ18.5ããª
ã¢ã«ïŒã®ïŒâïŒâïŒïŒ3aβïŒïŒïŒ6aβâããã©ã
ããâ2Hâã·ã¯ããã³ãããïœããã©ã³âïŒâ
ãªã³ãåŒãã®ïŒâïŒååç©ãã溶ããã液ãã
ããã¯ãããªããã20ã25âã«ãŠäžèšæº¶æ¶²äžã«æ»Ž
äžããã管ãŸãã¯ãã©ã¹ã³ã¯å¯éããã枩床ã¯ïŒ
ãïŒæéã®ãã¡ã«70âãŸã§äžæããããã®æ··åç©
ã¯ãã®æž©åºŠã«ãŠã24ã30æéããã¯ããããŸãŸã«
ããŠããããããã枩床ã80âã«ãŸã§äžæããå
å¿æ··åç©ã¯ãã®æž©åºŠã«ãŠ20ã24æéããã¯ããç¶
ç¶ãããšãæ··åç©ã¯éçœãã€è²ã瀺ããå·åŽã
ãŠãæ··åç©ãé žæ§ãšãã也ããïŒïœã®é ¢é žãœãŒã
ãå ããããããããããé ¢é žã®å€§éšåãæžå§èž
çºïŒ15ãã«ã40ã50âïŒãããæ®ãã¯é ¢é žãšãã«
ïŒ20ã30mlïŒã«æº¶è§£ãã飜åçé žå¡©æº¶æ¶²ã§æ°åäž
æ§ã«ãªããŸã§æŽæµããæ°ŽæŽæµç©ã¯ïŒÃ15mlã®é ¢é ž
ãšãã«ã§æœåºãããå䜵ããé ¢é žãšãã«æº¶æ¶²ã¯ã
ïŒÃïŒc.c.ã®å¡©æ°Žã§æŽããç¡«é žãã°ãã·ãŠã ã§ä¹Ÿç¥
ãã溶å€ãé€ãã4.5ã4.8ïœã®åž¯é»ãã€è²ã®æ²¹ã
ãããããèå±€ã¯ãããã°ã©ã枬å®ã«ããã°ãã
ãããçæç©ã®90ïŒ ã¯åŒïœã®ã©ã¯ãã³ãžãªãŒã«
ãžã¢ã»ããŒãã§ããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aαâãããµ
ãããâïŒÎ²âã¢ã»ããã·ã¡ãã«â5aâã¢ã»ã
ãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒâ
ãªã³ãåŒïœã®ååç©ã å®æœäŸïŒã«è¿°ã¹ãããã«ããªã³ã¹åå¿ãè¡ãªã
ããçžéç¹ã¯ããã©ã¹ã³ãéããé ¢é žãœãŒãæ·»å
åŸãé ¢é žã®ååã ããèžçºããããããïŒãïŒml
ã®ç¡æ°Žé ¢é žãåå¿çæç©ã«å ããããããïŒæé
40ã50âã§ãããã¯ããç¶ããŠããèžçºãããæ®
ãã¯å®æœäŸïŒã«æºããŠä»äžããããžã¯ããã¡ã¿ã³
ãšé ¢é žãšãã«ïŒïŒïŒã®æ··åç©ãçšãã·ãªã«ã²ã«ã«
ã©ã ïŒ200ã250ïœïŒäžã§åŒïœã®ããããååç©
ã溶é¢ãããšã次ã®ç©çç¹æ§ãæãã3.8ãïŒïœ
ã®çæç©ãããããïŒ ãαãïŒ ïŒ€ïŒ57.6ã±0.5ãïŒïŒ£ïŒ0.93ãã¯ããããª
ã«ã ïŒ ïŒ²fïŒ0.53ïŒGF254 ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é ž
ãšãã«äœ¿çšïŒ f0.38ïŒäžèšæ¿äžã»ãã³ãŒã³âé ¢é žãšãã«
ïŒïŒïŒã®æ··åç©äœ¿çšïŒ fïŒ0.17ïŒäžèšæ¿äžã»ãã³ãŒã³âé ¢é žãšãã«
ïŒïŒïŒã®æ··åç©äœ¿çšïŒ fïŒ0.71ïŒäžèšæ¿äžã»é ¢é žãšãã«âã¡ã¿ããŒ
ã«ïŒïŒïŒã®æ··åç©äœ¿çšïŒ IRïŒÎœ maxïŒïŒ2950ïŒ1770ïŒ1740ïŒ1360ïŒ
1230ïŒ1160ïŒ1060ããã³1030âïŒcm NMRïŒC13ïŒïŒã«ãã³å ã«ã¯éå ±åã®çµæãšæ§
é ã®å²ä»ã瀺ãããŠããã 176.75ïŒãåŒãã©ã¯ãã³ïŒïŒ171.15ïŒâOOâïŒïŒ170.80ïŒâOOâïŒïŒ84.01ïŒïœïŒ
ãåŒãïŒïŒ76.95ïŒïœïŒ ãåŒãïŒïŒ63.96ïŒïœïŒâH2âOOCâ CH3ïŒïŒ51.35ïŒïœïŒãåŒãïŒïŒ40.57ïŒïœïŒ ãåŒãïŒïŒ38.10ïŒïœâH2âïŒïŒ35.74ïŒïœïŒïŒ£H2âïŒïŒ21.05ïŒïœïŒâH3ïŒããã³20.79ïŒïœïŒ
âH3ïŒã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã«ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³
âïŒâãªã³ïŒåŒïœã®ååç©ïŒ 15mlã®ã¡ã¿ããŒã«äžã«768mgïŒïŒããªã¢ã«ïŒã®
åŒïœ ã®ã©ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒãã溶ãã
ã液ã«0.6ã¢ã«ã®ãããªãŠã ãšããã·ãã®ã¡ã¿ã
ãŒã«æº¶æ¶²ïŒmlã宀枩ã«ãŠæ·»å ããããã®åå¿ã¯45
ã50åã§å®äºãããèå±€ã¯ãããã°ã©ãã€æž¬å®ã«
ããã°ã溶液ã¯é¡ç®ååç©ããããããå«ãã§ã
ãªãããã®åŸã§ã0.3ã0.5ïœã®é ¢é žãããã¯ãã
ãªãããåå¿æ··åç©ã«æ»Žäžãããã€ç空èžçºã«ãŠ
ã¡ã¿ããŒã«ãé€å»ãããæ®ããé ¢é žãšãã«ãšã¡ã¿
ããŒã«ãšã®ïŒïŒïŒã®æ··åç©10mläžã«æº¶è§£ãããã€
ãã®æº¶æ¶²ã12ã15ïœã®ã·ãªã«ã²ã«ãããªãã«ã©ã
ãééããããã«ã©ã ã¯ïŒïŒïŒã®é ¢é žãšãã«ïŒã¡
ã¿ããŒã«æ··åç©ã®80ã100mlã«ãŠæŽæµããããã©
ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒããããŸãããªã³ã¹å
å¿ããã®æ®åããåŒã®äžé£œåã©ã¯ãã³ã®æ ¹è·¡é
ãå«ããªãã°ã溶é¢æ¶²ã®æåã®ïŒã25mlã¯å¥ã«é
ããããã次ã®35ã80mlãŸã§ã®æº¶é¢æ¶²ã¯ãåŒïœ
ã®ååŠçã«çŽç²ãªååç©ãå«ãããã®çåãèžçº
ãããšã400ã500mgã®çæç©ããããããå¯èœãª
ãã以äžã®ç²Ÿè£œåã«ãçæç©ãå°éã®ã¢ã»ããã
ãªã«ã«æº¶è§£ãå°ãæ¿ããŸã§ãšãŒãã«ã§ããããã
ãšã奜ãŸãããå·èµåº«å ã«ä¿åãããšããã圢ã®
çµæ¶ãšããŠçŽç²ãªçæç©ãæ¶åºããã ç©çç¹æ§ïŒ èç¹ïŒ117.5ã118.5â ãαãïŒïŒ ïŒâ43.4ã±0.5ã
ïŒïŒ£ïŒ1.4ïŒã¡ã¿ããŒã«ïŒ fïŒ0.1ïŒGF254ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é žãš
ãã«äœ¿çšïŒ fïŒ0.35ïŒäžèšæ¿äžãé ¢é žãšãã«ãšã¡ã¿ããŒ
ã«ïŒïŒïŒã®æ··åç©äœ¿çšïŒ IRïŒÎœ maxïŒïŒ3350ïŒ2900ïŒ1755ïŒ1070ãã
ã³1030cm-1 ãã®çæç©ã¯ä»ã®æ¹æ³ã§èª¿è£œãããçæ£ã®è©Šæ
ãšåäžã§ããããšã蚌æãããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã¡ãã«âïŒÎ±âãã
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³ïŒåŒïœã®ååç©ïŒ 15mlã¡ã¿ããŒã«äžã«åŒIcã®ã©ã¯ãã³ãžãªãŒã«ãž
ã¢ã»ããŒãã®910mgã»ïŒ3.58ã¢ã«ïŒã溶ããã液ã«
察ããïŒmlã®ã¡ã¿ããŒã«äžã®50mgã®ïœâãã«ãšã³
ã¹ã«ããªã³é žã溶ããã液ãæ·»å ãããã€åå¿æ··
åç©ã68ã72âã®æ¹¯æµŽäžã®èžçã³ã³ãã³ãµãŒä»ã®
ãã©ã¹ã³å ã§ããã¯ããã圢æããé ¢é žã¡ãã«ã
çåºããããåå¿ã¯ãçŽïŒã10æéããã€ãŠé ¢é ž
ã¡ãã«ïŒã¡ã¿ããŒã«æ··åç©ãçŽïŒãïŒmlçåºãã
ãåŸãå®äºããã湯济ã®æž©åºŠãé«ããããã«ã¡ã¿
ããŒã«ïŒãïŒmlãçåºããããªãæ®çããã¡ã¿ã
ãŒã«ã¯ãã³ãŒã³ãšã®å ±æ²žèžçã«ãã€ãŠé€å»ããã
ïŒå ±æ²žæ··åç©ã®æ²žç¹ïŒ56âïŒãã³ãŒã³ã¯æžå§èžçº
ããçæç©ã¯ãåå®æœäŸã©ãããã«ã©ã ã¯ããã
ã°ã©ãã€ã§ç²Ÿè£œãããé¡èšååç©ã¯570ã580mgã
ããããããããçæç©ã®ç©çç¹æ§ã¯å®æœäŸïŒã®
ååç©ã®ãããšçããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aαâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«â5aâã¢ã»
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³ïŒåŒïœã®ååç©ïŒ åŒïœã®ã©ã¯ãã³ã»ãžãªãŒã«ã»ãžã¢ã»ããŒã
600mgïŒ2.36ããªã¢ã«ïŒã15mlã®ã¡ã¿ããŒã«ã«æº¶
ãããã液ã«ãã¡ã¿ããŒã«ïŒmläžã«40mgã®ïœâã
ã«ãšã³ã¹ã«ãã³é žã溶ããã液ãå ããåå¿æ··å
ç©ã¯å®€æž©ã«ãŠïŒã10æéããã¯ããããåå¿ã¯è
å±€ã¯ãããã°ã©ãã€ã«ããå¶åŸ¡ãããã GF254ã·ãªã«ã²ã«âéŒæ¿äžã«æ€åºãããæ··åäž
åäž»çæç©ã®ïŒ²fïŒã¬ãŒãã»ãã¢ã¯ã¿ãŒïŒå€ã¯æ¬¡
ã®ãšããã§ããïŒ ãè¡šã åå¿å®çµåŸãæ··åç©ã¯å®æœäŸïŒã«è¿°ã¹ãããã«
ä»äžãããããããããéé»è²æ²¹ã¯æº¶é¢å€ãšããŠ
é ¢é žãšãã«ïŒã¡ã¿ããŒã«ãçšãã50ã100å容é
ã®ã·ãªã«ã²ã«ã«ã©ã äžã§ã¯ãããã°ã©ãã€ã«ã
ããåºã ã«ã¡ã¿ããŒã«æ¿åºŠãïŒïŒïŒã®å²åãã
ïŒïŒïŒãŸã§å¢å ãããçåã¯èå±€ã¯ãããã°ã©ã
ã€æž¬å®ãè¡ãªããåäžçæç©ãå«ãçåã¯ãŸãšã
ãŠãèžçºãããããããŠãåŒIaã®ã©ã¯ãã³ãžãªãŒ
ã«ã¢ãã¢ã»ããŒãã310mgïŒ62ïŒ ïŒããããã å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã¡ãã«âïŒÎ±âãã
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³âãã«ã ã¢ã«ãããã¢ã»ã¿ãŒã«ãïŒR5ãš
R6ãæ°ŽçŽ ã§ããïŒè¬åŒIxã®ååç©ïŒ ïŒïœã»ïŒ5.88ããªã¢ã«ïŒã®IdåŒã®ã©ã¯ãã³ãžãª
ãŒã«ãšïŒïœã»ã®ãã©ãã«ã ã¢ã«ããããšãã20ml
ã®ãã³ãŒã³äžã§æ¯ãšããããããããæ°æ»Žã®äžã
ãåããŠçŽ ãšãŒãã«ååç©ãå ããããããã©ã¹
ã³ãéãã宀枩ã«ãŠïŒæ¥éæŸçœ®ãããïŒæ¥åŸãå
å¿æ··åç©ãããªãšãã«ã¢ãã³ã§äžåããæ²æ®¿ãã
å¡©ãå¥ãã溶å€ãèžçºããæ®çæ²¹ã¯ãšãŒãã«ïŒ
ãããµã³æ··åç©ããåçµæ¶ãããé¡ç®ååç©ãã
ãããã fïŒ0.37ïŒé ¢é žãšãã«ïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœãã©ã³â
ïŒâãªã³âãã³ãºã¢ã«ãããâã¢ã»ã¿ãŒã«
ïŒR5ãããšãã«åºã§R6ãæ°ŽçŽ ã§ããäžè¬åŒïœ
ã®ååç©ïŒ ïŒmlã®ãã³ãŒã³äžã«722mgïŒ2.71ããªã¢ã«ïŒã®
åŒIeã®ã©ã»ãäœãžãªãŒã«ãžã¢ã»ããŒãã溶ããã
液ã«å¯ŸãïŒmlã®ãã³ãŒã³äžã«ãã³ãºã¢ã«ããããž
ã¢ã»ã¿ãŒã«ã溶ããã液ãæ··åãããã®åå¿æ··å
ç©ã«0.2mlã®ã¡ã¿ããŒã«ã«æ¿ç¡«é žïŒmgã溶ããã
液ãå ãããåå¿æ··åç©ã¯15ã20æéå ç±ããã
é ¢é žã¡ãã«ã¯é£ç¶çã«çåºããããåå¿å®çµæã«
ã¯ãæ··åç©ã¯ããªãšãã«ã¢ãã³ã§äžåããæ²æ®¿ã
ãå¡©ãå¥ãã液ã¯èžçºãããæ®çç©ã¯ç¡æ°Žãš
ãŒãã«10mläžã«æº¶è§£ããç³æ²¹ãšãŒãã«ãæ·»å ããŠ
çµæ¶åãããé¡ç®ååç©ãããããã f0.51ïŒé ¢é žãšãã«ïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³
âïŒâãªã³âã¢ã»ãã³ã¢ã»ã¿ãŒã«ïŒR5ïŒR6ã
ã¡ãã«ã§ãããäžè¬åŒïœã®ååç©ïŒ 10mlã®ãã³ãŒã³äžã®åŒIdã®ã©ã¯ãã³ãžãªãŒã«ã®
102mgã»ïŒ0.56ããªã¢ã«ïŒã«å¯ŸããŠãïŒmlã®ïŒïŒïŒ
âãžã¡ãããªãã·âãããã³ïŒã¢ã»ãã³ãžã¡ãã«
ã¢ã»ã¿ãŒã«ïŒããã³25mgã»ã®ïœâãã«ãšã³âã¹ã«
ããªã³é žïŒæ°Žåç©ãå ãããããåå¿æ··åç©ã¯ã
å ±æ²žæ··åç©ãçåºé€å»ããããã«75ã80âã«ä¿æ
ãããããã¢ã»ãã³ïŒãžã¡ãã«ã¢ã»ã¿ãŒã«ã¯æ»ã
ãããïŒã10æéåŸãåå¿ã¯å®çµãããåå¿æ··å
ç©ãèžçºãããšãæèµ€è²æ²¹ããããããããïŒml
ã®ãšãŒãã«ã«æº¶ãããããããïŒmlã®ç³æ²¹ãšãŒã
ã«ãå ããŠçµæ¶åããã57mgã®é¡èšååç©ããã
ããã fïŒ0.50ïŒGF254ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é žãš
ãã«äœ¿çšïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβïŒïŒâã
ããµãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±
âããããªãã·â2Hâã·ã¯ããã³ã¿ãïœãã
ã©ã³âïŒâãªã³âïŒåŒIdã®ååç©ïŒ ïŒmlã®36ã38ïŒ ãã«ã ã¢ã«ããã溶液ã«å¯Ÿã
ãŠãïŒmlã®æ¿ç¡«é žãå°ããã€å·åŽãããã¯ãããª
ããæ·»å ãããã®æ··åç©ã«ïŒïœïŒ8.0ããªã¢ã«ïŒ
ã®ïŒÂ±ïŒâïŒïŒ3aβïŒ6.6aβâããã©ãããâ
2Hâã·ã¯ããã³ã¿ããïœããã©ã³âïŒâãªã³ã
å ãããåå¿æ··åç©ãå«ããã©ã¹ã³ãéãã70â
ã«70ã80æéä¿æããããããã垯é»ãã€è²æ²¹ç¶
ç©è³ªãããã©ã¹ã³éæŸåŸãïŒïœã®çé žãœãŒãäžã«
泚ããæžæ¿ç©ã¯å®å šã«é ¢é žãšãã«ã«ãã€ãŠæœåºã
ããå䜵ããé ¢é žãšãã«æœåºç©ã¯å¡©æ°ŽæŽæµãç¡«é ž
ãããªãŠã äžã®ä¹Ÿç¥ããåŸãé ¢é žãšãã«ã¯èžçºã
ããæ®çé»è²æ²¹ã¯äž»æåãšããŠã®åŒIdã§ç€ºããã
ã©ã¯ãã³ãžãªãŒã«ãšãããã³ïŒ²ãæ°ŽçŽ ã瀺ãåŒ
ã®ååç©äžŠã³ã«æ°çš®ã®æªç¢ºèªç©è³ªããæã€ãŠã
ããåŒïœã®ååç©ã¯å®æœäŸïŒã«ã®ã¹ãããã«ã
ã«ã©ã ã¯ãããã°ã©ãã€ã§åé¢ããããåŒïœã®
ããããã©ã»ãäœååç©ã®ç©çæ§ç¶ã¯èç¹ãé€ã
ãŠã¯ãå®æœäŸïŒã«ãŠããããïŒâïŒâå·Šå³ç·ãžãª
ã«ã®æ§ç¶ãšåçã§ãããã©ã»ãäœçæç©ã®èç¹ã¯
91ã92âã§ããã
ã³ã»ãžãªãŒã«èªå°äœã«é¢ããããã®ãããªååç©
ã¯ã³ãŒã¬ã€ïŒCoreyïŒã®ããã¹ã¿ã°ã©ã³ãžã³åæ
ã«ãããäžéäœãšããŠæçšã§ãããæ¬é¡çºæã¯ãŸ
ããããååç©ã®èª¿è£œæ¹æ³ã«ãé¢ããã 倩ç¶ããã¹ã¿ã°ã©ãžã³ã¯å å çµèãã«ã¢ã³ã®é¡
èãªçç©åŠç掻æ§ãæãã矀ãæ§æããã倩ç¶ã
ãã¹ã¿ã°ã©ã³ãžã³ãåé¢ããããã€ãããã®æ§é
ã調ã¹ããã1960幎ããå§ãŸãã巚倧ãµã€ãºã®ç
究äœæ¥ãããããååç©ãåæããæ¹æ³ã確ç«ã
ãããšãšãŸãé¡äŒŒæ§é ã®ååç©äžããããããã¹
ã¿ãã€ãâãããããã®è¬åŠç掻æ§ãè©äŸ¡ãã
ãJ.A.C.S.ïŒ93ïŒ4326ïŒ1971ïŒãããã«èª¿è£œããã
ãšãé²ããããŠãããããã¹ã¿ã°ã©ã³ãžã³ã®åœå
ãšççåŠç掻æ§ããã³ãããã®åææ¹æ³ã¯ãå€æ°
ã®è«æãã®ä»ã®åè¡ç©ïŒããšãã°ãArzneimittel
Forseh.25ïŒ135ïŒ1975ïŒïŒã«ãŠæãã«ãããŠã
ãã ç«äœååŠçåé¡ãéçšæ§ããã³éèŠæ§ã®è§£æ±ºã«
é¢ããŠã¯ãJ.A.C.S.ïŒ91 5675ïŒ1969ïŒïŒä»äž
èªã92ïŒ397ïŒ1970ïŒãããã³ä»äžè©Š93ïŒ1490
ïŒ1971ïŒã«èšèŒã®åæããçš®ã ã®å šåææ³ã®äžã§
ãé¡èãªå°äœãå ãããã€ãŸãå·¥æ¥åèŠä»¶ããå
足ããããã®åæã®æçµè£œåã¯PGF2ãã§ããã
ããã¯ä»ã®è¬çåŠçã«éèŠãªå€©ç¶ããã¹ã¿ã°ã©ã³
ãžã³ãããªãã¡PGF1ïŒPGF2ïŒPGF1ãããŸãã¯
PGF1ãã«å€æããããšãã§ããã äžèšåæäžããŠã€ãããïŒWittigïŒåå¿ãäºé
çµåã®ç«äœéžæç圢æçšã«äœ¿çšãããããŠã€ãã
ãåå¿ãå©çšãããã®ã¯ãã¢ãªã«ã¢ã«ã³ãŒã«éšå
ãå«ãåŽéäžã«å¿ èŠãªãã¹ãããŒãïŒå®å®åãã
ã€ãªãïŒãšãã©ã³ã¹åäºéçµåã圢æãããåæ
ã«ä»ã®åŽéäžã«ïŒâã«ã«ããã·ããã«ããªããšã
ã«ãã¹ãããŠã ãããã€ãïŒæŽ»æ§ã€ãªãïŒããçº
çãããã¹ãã©ã³ãšã·ã¹åäºéçµåã圢æãããª
ããã°ãªããªããšããããã¹ã¿ã°ã©ã³ãžã³ç¹æã®
ååŠæ§é ã«èµ·å ããå¿ èŠæ§ããã§ããã ãã®åæã®åºæ¬äžéäœã¯ãPGF2ãå ã«ããã
ããã«ãåäžã®çµ¶å¯Ÿçããã³çžå¯Ÿçé åã«å¯ŸããŠ
äžæã®ïŒã€ã®äžå¿ãæãããããããâCoreyã¢
ã«ãããâã§ããããã®åææ³ã«ããã°ãåŒã®
ã¢ã«ããã ã¯ã次ã®ç¥å³ã«ç€ºãããããã«ã åŒã®ã¢ã«ã³ãŒã«ãé žåããããšã«ãã€ãŠèª¿è£œã
ããã äžè¬åŒã®ã¢ã«ã³ãŒã«èª¿è£œçšã®ç«äœååŠçå¶åŸ¡
åå¿ã¯æ¬¡ã®ç¥å³ã«ç€ºãããŠããïŒ ãã®åæã®éåžžã«å€æ°ã®æ¹è¯å€æŽã¯ãçš®ã ã®å
è¡ç©ãç¹èš±ã§å ¬åãããŠããããããšãã°J.C.S.
Chem.Comm.151ïŒ1974ïŒïŒåè©Š642ïŒ1974ïŒïŒ
åè©Š39ïŒ1975ïŒïŒJ.A.C.S.96ïŒ5261ïŒ1974ïŒãã ããããªããããããã®å€æŽã¯ã©ãããäžè¬åŒ
ã®ãããµãããâïŒ(H)âã·ã¯ããã³ã¿ããïœã
ãã©ã³èªå°äœã®é©åœãªç«äœç°æ§äœã6aïŒïŒ³ïŒïŒ3a
ïŒïŒ²ïŒïŒïŒïŒïŒ³ïŒïŒïŒïŒïŒ²ïŒãã圢æãããçºã«å¿ èŠ
ãªäžé£ã®åå¿å·¥çšã»å€æŽãããã®ã§ã¯ãªãããã
ããå Žåã次ã®åå¿ã次ã®é åºã§çšããããïŒç«
äœçã«å¶åŸ¡ããããã€ã«ã¹ãŒã¢ã«ããŒïŒDiels
AlderïŒåå¿ã«ãã€ãŠèª¿è£œããããã·ã¯ããïŒïŒ
ïŒïŒïŒããããã³âãªã³èªå°äœã¯ãé åèŠåæ§ã®
ãã€ã€ãŒâããªã³ã¬ãŒïŒBaeyerâVillingerïŒé ž
åãããããããÎŽâã©ã¯ãã³ã¯ããããªãã·é ž
ãŸã§å æ°Žå解ããããããããšãŒãâã©ã¯ãã³åœ¢
æåå¿ããããããšãäžè¬åŒã®äžèšååç©ãã
ãããã ããããªããããã€ãŒãïŒã«è¿°ã¹ãåæã¯äžå©
ãªç¹ãå€ãããã®æ¹æ³ã§äžè¬åŒã®ååç©ã調補
ããããšã¯ãåå¿æ®µéæ°ãå€ãããã€è©Šè¬ãåŸã«
ãããïŒããšãã°ãαâã¯ããã¢ã¯ãªã«é žãšã¯ã
ãã¡ãã«ã»ãã³ãžã«ãšã¹ãã«ã¯ãã€ãšå€æ°ã®åå¿
段éãæããåæã«ãŠèª¿è£œããããïŒãŸãæ¯æ§ã
ããïŒããšãã°ãã¿ãªãŠã ååç©ãããªãããã³
æ°ŽçŽ åç©ïŒãšããäºå®ã«åºã¥ãã極端ã«è€éã§ã
ã€çµè²»ããããã ã³ãŒã¬ã€åæäžã®äžè¬åŒã®ååç©ã眮ãæã
ããåŒã®äžéäœã¯ããã€ãŒãïŒã«ç€ºãæ¹æ³ãJ.
A.C.S.ïŒ95ïŒ6853ïŒ1973ïŒãã«ãã€ãŠèª¿è£œããã
ãšãã§ããã ããããªããããã®åæã¯ãŸãå€æ°ã®åå¿æ®µé
ãããªãããã€ãšããã·åã«ãã€ãŠããããç°æ§
äœã¯ã¯ãããã°ã©ãã®ã«ã©ã ã§åé¢ããªããã°ãª
ããããã®ããã«ãã®æ¹æ³ã¯è€éã§ããã€çµè²»ã®
ããããã®ã§ããããšããããã æ¬çºæè ã¯é©ãã¹ãããšã«ãäžè¬åŒ ãåŒäžãR3ãšR4ã¯åçš®ãŸãã¯ç°çš®ã§ãããã
ã€æ°ŽçŽ ã§ãããããŸãã¯ä»»æã«ïŒåãïŒåãŸãã¯
ïŒåã®ããã²ã³ã«ãã€ãŠçœ®æãããŠããŠãããäœ
çŽã¢ã«ã«ãã€ã«åºã瀺ãããã€R3ãšR4ãšã¯å ±ã«
éåããŠR5ââR6åºã圢æããŠãããR5ãšR6
ã¯æ°ŽçŽ ãã¡ãã«åºããã³ããšãã«åºããéžæã
ããR5ããã³R6ã®ããããäžã€ãããšãã«åºã§
ããå Žåã«ã¯ä»ã®äžã€ã¯æ°ŽçŽ ã瀺ãã ã«ãŠç€ºãããååç©ïŒåŸèšã®åŒã«è©²åœïŒããæ¬
é¡çºæã®æ¹æ³ã«ããã°ãã¯ããã«åçŽãªæäœã§å
æããããšãã§ããããšãèŠåºããã æ¬é¡çºæã¯ãããªã³ã¹ïŒPrinsïŒåå¿ãç«äœèŠ
å¶çãã©ã³ã¹âä»å ç¹æ§ãæãããChem.ReWs.
51ïŒ505ïŒ1952ïŒãããšãå©çšãããã®ã§ãããé ž
觊åªã®ååšäžã§ãã«ã ã¢ã«ãããããªã¬ãã€ã³ã«
ä»å åå¿ããããªã³ã¹åå¿ã®ç«äœååŠãšåå¿æ©æ§
ã¯ããã§ã«åºãè©äŸ¡ãããŠããããBull.Chem.
Soc.Chem.FranceïŒ357ïŒ1952ïŒã ããªã³ã¹åå¿ã¯å¿ ãããé åèŠå¶çã§ãªããšã
ãŠããäžè¬ã«ç«äœèŠå¶çã«é²è¡ãããåå¿åªäœäž
ã®é žã¯äºéã®åœ¹å²ããªããšããïŒé žã¯åäœããªã«
ã ã¢ã«ããããšåå¿ãã第ïŒåå¿æ®µéã§äºéçµå
ã®Ïâé»åç³»ãæ»æããã¡ãããŒã«ã«ããªã³ïŒïŒ
CH2OHïŒãã€ããããã€ä»æ¹ããªã«ã ã¢ã«ãã
ãéåäœïŒãã©ããªã«ã ã¢ã«ããããããªãªãã·
ã¡ãã¬ã³ïŒã®è§£éååå¿ã«ããã觊åªãšããŠäœçš
ãããé žãšããŠã¯ããšãã°ãç¡«é žããªã³é žãäžã
ãåããŠçŽ âãšãŒãã«åç©ãªã©ãçšããããã ããªã³ã¹åå¿ã®æçµçæç©ã¯ã䜿çšãã溶å€
ïŒé ¢é žãæ°Žãéãããã³æ§æº¶å€ïŒã«å€§ããäŸåã
ããäžè¬ã«çšããããé ¢é žã氎溶å€äžã§ã¯ãäž»ç
æç©ã¯ã䜿çšãªã¬ãã€ã³ããèªå°ããããããã
ã·ã«âã¡ãã«ã¢ã«ã³ãŒã«ãšããã®ã¢ã»ãã«åç©ã
ãã³ïŒïŒïŒâãžãªããµã³èªå°äœã§ããã æ¬é¡çºæã®æ¹æ³ã«ãããŠãåŒã®å ¬ç¥ã®ïŒïŒ
3aïŒïŒïŒ6aâããã©ãããâ2Hâã·ã¯ããã³ã¿
ããïœããã©ã³âïŒâãªã³ ïŒãã®ååç©ã®ä»ã®éçšåïŒã·ã¹âïŒâãªããµ
âãã·ã¯ããïŒïŒïŒïŒïŒããªã¯ãâïŒâãšã³âïŒ
âãªã³ïŒãšãã®å åŠæŽ»æ§ã®åœ¢æ ãåŒã®ïŒâïŒã
ãã³ïŒïŒïŒååç©ã§ããïŒâïŒâã6aïŒïŒ³ïŒïŒ3a
ïŒïŒ²ïŒãâããã³ïŒïŒïŒâã6aïŒïŒ²ïŒïŒ3aïŒïŒ³ïŒãâ
ç°æ§äœããããªã³ã¹åå¿ãè¡ãªãå Žåã®ãªã¬ãã€
ã³ãšããŠäœ¿çšããããäžèšååç©ã¯TeTr.
Lett.307â310ïŒïŒ1970ïŒã«å®äŸãšããŠæ瀺ãããŠ
ããã åŒã®ååç©ã¯ã·ã¯ããã³ã¿ãžãšã³ã«ã¢ããŒãŸ
ãã¯ãžâã¯ãã«ãšãã¬ã³ãä»å ãããããŸãã¯åŒ
ã®å ¬ç¥ã®ïŒïŒïŒïŒïŒïŒïŒãããâïŒâãšã³âïŒ
âãªã³ ãéé žåæ°ŽçŽ ã«ãã€ãŠé žåããããšã«ããïŒåå¿
段éã§èª¿è£œã§ãããïŒïŒïŒâαâã¡ãã«âãã³ãž
ã«ã¢ãã³ã«ããåŒã®ååç©ã®åå²ã¯ãæç®ã«èš
è¿°ãããŠãããïŒJ.A.C.S.ïŒ95ïŒ6832ïŒ1973ïŒïŒã
åŒã®ååç©ã®å·Šå³åã®èª¿è£œã®ããã«ã¯ãïŒæ®µé
ãããªãäžæåæãJ.A.C.S.ïŒ95ïŒ7171ïŒ
1973ïŒïŒã«èšèŒãããŠãããåŒã®ååç©ã¯ãã®
ã©ã»ã圢ã§ããå åŠæŽ»æ§ïŒïŒïŒããã³ïŒâïŒåœ¢ã§
ãã åæ§ã«çš®ã ã®ããã¹ã¿ãã€ããããã¹ã¿ãã€ãäž
éäœã®åæã«ãããŠé¡èã«æ±ºå®ç圹å²ãæŒããŠã
ãããTetr.Lett.4753ïŒ1971ïŒïŒåè©Š3091
ïŒ1973ïŒïŒJ.A.C.S.ïŒ95ïŒ6832ïŒ1973ïŒïŒTetr.
Lett.2439ïŒ1974ïŒãäžèšååç©ã倩ç¶ã®ããã¹ã¿
ã°ã©ã³ãžã³ã«å€æããããã«ã¯ãããããªããã
ãã éåžžã«æ£ç¢ºãã€è€éãªåå¿æ¡ä»¶ã§ã®ã¿èª¿è£œã
ãããã€é«åºŠã®ããã€ãã®é£ç¶ã¯ãããã°ã©ã粟
補ã®äžã§ã€ãããããªããŠã ã»ãžã¢ã«ã±ãã«ã»ã
ãŠãã¬ãŒããŸãã¯æ··åããŠãã¬ãŒãã®å ±åœ¹ä»å ã«
åºã¥ãè€éãªåå¿ãèšèŒãããŠããã ãã§ããã æ¬é¡çºæã®çµæãšããŠãç¡«é žè§Šåªã®ååšäžã§ã®
åŒã®ã©ã»ãäœãŸãã¯å åŠæŽ»æ§ååç©ã®åå¿ïŒã
ãªã³ã¹åå¿ïŒã¯ãé ¢é žåªäœäžã§å®æœãããå Žåã
é åèŠå¶çã§ããããã€äž»çæç©ãšããŠåŒïœã®
ååç© ãããããåéã§ããããäžæ¹åŒïœ ã¯åå¿æ¡ä»¶ã«ããïŒã10ïŒ ã®éã«ãããããã
ãŠãåŒïœããã³ïœã®éšåçã«ã¢ã»ãã«åãã
ãååç©ã®åœ¢æã¯ã枩床ãé©çšããããã«ã ã¢ã«
ãããããã©ããªã«ã ã¢ã«ãããããã³ããªãªã
ã·ã¡ãã¬ã³ã®å質ããã³é ¢é žæº¶åªã®æ°Žå«æéã®é¢
æ°ã§ããããããã®éšåã¢ã»ãã«åç©ãé€å»ãã
ã«ã¯ãããããå«ãåå¿çæç©ããã®ãŸãŸäŸãã°
ç¡æ°Žé ¢é žã«ãã€ãŠã¢ã»ãã«åãã以å€ã«æ¹æ³ããª
ãã ããªã³ã¹åå¿æ©æ§ã®çµæãåŒïœã§ç€ºãããå
åç©ã¯ãããã³è§Šåªåå¿ã«ããã¢ã·ã«åºç§»ååå¿
ã«ææã§ããããã«åŒïœã§ç€ºãããååç©ãç
æãããéšåã¢ã»ãã«åã©ã¯ãã³ãžãªã«ã®äž¡è
ã¯ããããã³äŸèäœè§Šåªã®ååšã§ã¢ã»ãã«åã§ã
ããããããããšã¹ãã«åäžã«åœ¢æããæ°Žã¯ç³»å
ã«æ®ããããããŠå¹³è¡¡æ··åç©ãåå¿æ¡ä»¶ã§ããŸã
çµæç©ãšããŠããããã åŒïœãšïœã®ååç©ã®ã¢ã»ãã«åé床ã¯é¡è
ã«ç°ãªããæåŸ ãããããã«ãïŒçŽããããã·åº
ã¯ïŒçŽããããã·ã«ããæ°åã®é床ã§ã¢ã»ãã«å
ããããïŒçŽããïŒçŽæ¹åãžã®ã¢ã·ã«åºç§»åé床
ã¯ããã®åå¿æ¹åãžã®ç§»åé床ããã倧ããã éšåã¢ã»ãã«åçæç©ã®åœ¢æã¯ãã¢ã»ãã«åç
æç©ãã¢ã«ã«ãªã¢ã«ã³ãã·ããã¢ã«ã«ãªçé žå¡©ã
ãŸãã¯é žã«ããæ¥è§Šçå æ°Žå解ãŸãã¯ã¢ã«ã³ãŒãª
ã·ã¹ãããããšãããªããã®äžå©çããªããã¢ã«
ã³ãŒãªã·ã¹ã¯ã倧äœ10ã20ã¢ã«ïŒ ã®é žè§Šåªã®ååš
äžã§éè¡ãããããé žã«ããæ¥è§Šã¢ã«ã³ãŒãªã·ã¹
ã¯ãé±é žãŸãã¯ã¢ãªãŒã«ã¹ã«ãã³é žè§Šåªã®ååšäž
ã§çæããé ¢é žã¢ã«ãã«ãèžçããããšã«ãã€ãŠ
è¡ãªãããšãã§ãããã¢ã«ã³ãŒãªã·ã¹ã¯ãããã
ãé ¢é žã¡ãã«ã䟿å©ãªäœæ²žç¹ãæãããã€ããã
ãŠå®¹æã«èžçºããããšãã§ããããã奜ãã§ã¡ã¿
ããŒã«ã«ãã€ãŠå®æœããããããªã³ã¹åå¿ã«ãã€
ãŠããããçæç©æ··åç©ã¯é žãŸãã¯ã¢ã«ã«ãªæ§å
æ°Žå解ã«ãããåŒã®ã©ã¯ãã³ãžãªãŒã«ã調補ã
ããã åŒã®ååç©ã¯å ¬ç¥ã§ãããïŒJ.A.C.S.ïŒ93ïŒ
1491ïŒ1971ïŒïŒãã®åŒçšæç®äžã«ããã®ååç©ã®
ä»ã®èª¿è£œæ³ããã®èç¹ããã³æå 床ãèšèŒãããŠ
ãããæ¬é¡çºæã®æ¹æ³ã«ãã調補ãããåŒã®å
åç©ã®ç©çç¹æ§ã¯æç®äžã«çºè¡šããããã®ãšåç
ã§ããã åŒã®å åŠæŽ»æ§ååç©ãé žè§Šåªã«ããã¡ã¿ããŒ
ãªã·ã«ã«ãã€ãŠèª¿è£œãããå Žåã溶å€èžçºåŸãæ®
åããçµæ¶æ§ç²çæç©ã®éžæçã¢ã»ãã«åã«ãã€
ãŠåŒã®ååç©ã«ïŒãã³ã¬ãªãŒç¹èš±CIâ1652ïŒã
ãŸãéžæçé žåã«ããããã以äžã®ãªããã®ç²Ÿè£œ
ãè¡ãªãããšãªãã«ãåŒã®ååç©ãšããããšã
ã§ããã ã¢ã«ã«ãªã¢ã«ã³ãã·ããŸãã¯ã¢ã«ã«ãªçé žå¡©ã«
ããæ¥è§Šã¢ã«ã³ãŒã·ã¹ã¯åžžæž©ã§éè¡ã§ããããã
ãããã®å Žåã溶å€èžçºåã®äžåãããšãã°ã·ãª
ã«ã²ã«ã«ã©ã ããã®æ··åç©ãééãããããšã«ã
ããçããå¡©é¡ãé€å»ããã«ã¯å¥œéœåã§ããã åŒã®ååç©ã¯ãé ¢é žãšãã«ãé ¢é žãšãã«ïŒã
ããµã³ãŸãã¯ã¢ã»ããããªã«ãšãŒãã«ããåçµæ¶
ã§ãããåçµæ¶åŸãåŒã®ååç©ã¯80ã90ïŒ ã®å
éã§ãããããïŒåŒã®åºçºç©è³ªã«åºããŠèšç®ïŒ ããªã³ã¹åå¿ã«ãã€ãŠããããäž»çæç©æ··åç©
ã¯ããã®ãŸãŸã®ã¢ã»ãã«åã«ãããã»ãšãã©å®é
çã«åŒïœã®ã©ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒãã«å€
æã§ãããããããŠãæ°ååç©ã§ããåŒïœã®å
åç©ã¯ãåŒã®ååç©ããåºçºããå Žåã90ã95
ïŒ ã®åéã§ããããã ããªã³ã¹åå¿ã«ãŠèª¿è£œãããåŒïœã®ååç©ã®
絶察çããã³çžå¯Ÿçé åã蚌æããããã«ãçºæ
è ã¯ãŸããã€ãŒãïŒã«ç¥ç€ºããåå¿ã«åŸã€ãŠãã®
ååç©ãã€ãã€ãã ã³ãŒã¬ã€åæã«ãŠå ¬ç¥ã®åŒã®ãšãŒãã©ã¯ãã³
ããåºçºãããã®ååç©ã«æã®åœ¢ããªãäžå¿éšã«
ã¯é¢ä¿ã®ãªãïŒé£ã®å€æåå¿ãè¡ãªã€ãããã®æ
å æ§ãæããããããŠããããååç©ã¯ãããªã³
ã¹åå¿ã«ããåŒã®ïŒâïŒååç©ããã€ãããã
åŒIcã®å·Šæå ååç©ãšåäžã§ãã€ãã åŒïœã®ååç©ã¯ãåŒïœã®ã©ã¯ãã³ãžãªãŒã«
ãžã¢ã»ããŒãã®éšåè±ã¢ã»ãã«åã«ãã€ãŠèª¿è£œã
ããããã®åŒïœã®ååç©ã¯åŒã®ååç©ãšåæ§
ã®æ¹æ³ã§ã³ãŒã¬ã€åæã«äœ¿çšãåºæ¥ãããã®è±ã¢
ã»ãã«åã¯äžè¿°ã®ã¢ã·ã«åºç§»åã«åºã¥ãã絶察ç
ã«éžæçãªãã®ã§ã¯ãªããããããªããããã®å
å¿æ··åç©äžã®åŒïœãšïœã®ååç©ã®éã¯ãæé©
ã®ãããã³éãã¢ã«ã³ãã·ããšçé žå¡©ã®æ¿åºŠãå
å¿æéåã³ããªã«ããããåå¿æž©åºŠãã¿ãã ãã
ãšã«ãã€ãŠæ¥µå°åã§ãããéšåã¢ã»ãã«ååŸãåŒ
ïœã®ååç©ã¯ã«ã©ã ã¬ã¹ã¯ãããã°ã©ãã€ã«ã
ããåŒïœãšïœã®ååç©ããåé¢ã§ããããã®
åé¢ã¯ã溶é¢å€ãšããŠã¡ã¿ããŒã«æ¿åºŠãå¢å ããŠ
è¡ãé ¢é žãšãã«ïŒãšã¿ããŒã«ãçšããåŸé 溶é¢æ³
ã«ããã·ãªã«ã²ã«ã«ã©ã äžã§è¡ãªãããããŸãã
第ïŒçåã¯åŒïœã®ååç©ãå«ã¿ãç¶ããŠåŒïœ
ã®ååç©ããããŠããããåŒïœã®ååç©ããã
ããã å°éã®ãªã³ãªãã·ã¯ãã©ã€ã觊åªã®ååšã§ãå¯
éç³»å ã§å®€æž©ã«ãŠæ°æ¥éãåŒïœã®ããããã©ã¯
ãã³ãžãªãŒã«ããã³ãŒã³å ã§éå°éã®ãã©ãã«ã
ã¢ã«ããããšåå¿ãããå ŽåãR5ãšR6ãæ°ŽçŽ ã§
ããäžè¬åŒïœã®ïŒïŒïŒâãžãªããµã³èªå°äœ ãããããããã®çæç©ã®æ ¹è·¡éã¯ããŸãããªã³
ã¹åå¿ã®çæç©äžã«æ€åºã§ãããç°ç¶ã¢ã»ã¿ãŒã«
ã®åœ¢æã«å°ãäžèšãããŸãã®åå¿ã¯ããŸãä»ã®ã¢
ã«ããããã±ãã³ã«ãã€ãŠãéè¡ããããããã
ãŠããã«ã ã¢ã«ãããããã³ãºã¢ã«ããããŸãã¯
ã¢ã»ãã³ã«çœ®ãæããå Žåãé¡èã«ãR5ãããš
ãã«åºã§ããã€R6ãæ°ŽçŽ ã§ãããããŸãã¯R5ãš
R6ãåã ã¡ãã«åºãè¡šããäžè¬åŒïœã®ååç©
ããããããäžè¬åŒïœã®ããããŠããããåå
ç©ã¯ä¿è·ããã圢ã®åŒïœã®ååç©ã®ïŒåã®ãã
ããã·ã«åºãå«ãæçšãªäžéäœã§ãããä¿è·ãã
ãç°ç¶ã¢ã»ã¿ãŒã«ã¯ãããããªããããã ãããª
é žåªäœäžã§å®¹æã«æ¶å»ã§ããã åŒã®ååç©ã«å¯ŸããŠå®éãããããªã³ã¹åå¿
ã«ãããŠãé ¢é žã¯ä»ã®äœçŽã¢ã«ã«ã³ã«ã«ããã·ã«
é žã«çœ®æãããããŸããïŒåãïŒåãŸãã¯ïŒåã®
ããã²ã³ãå«ãäœçŽã¢ã«ã«ã³ã«ã«ããã·ã«é žã«ã
ã€ãŠåå¿ãè¡ãªããããšããR3ãšR4ãšã¯æ°ŽçŽ ã
ãã³ïŒãŸãã¯é©åœãªã¢ã·ã«åºãè¡šããäžè¬åŒã®
ååç©ãããããã ãã®åå¿ã¯ãŸãé žããªããšãéè¡ãããããã®
å Žåãæ¿ç¡«é žè§ŠåªãšããããåŒã®ååç©ããã
ã«ã ã¢ã«ããã氎溶液äžã«å ããããã å¯éç³»ã¯70âã«ãŠã70ã80æéãããããä¿æ
ããããäž»çæç©ã¯åŒïœã®ååç©ã§ãããã
R5ãšR6ãæ°ŽçŽ ã§ããåŒïœã®ååç©ããŸãå°é
ãããããåŒïœã®ååç©ã¯æ··åç©ããã¯ããã
ã°ã©ãã€ã«ãã€ãŠåé¢ããããã次ã®å®æœäŸã¯å
ãªãåŒäŸã«ãããããªãã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒ6aβâããã©ãããâ
2Hâã·ã¯ããã³ãããïœããã©ã³âïŒâãªã³
ã«ãã«ã ã¢ã«ãããã®ä»å å°å ¥ã§ããã¬ã©ã¹ç®¡ãŸãã¯ã¬ã©ã¹æ ãåããã
ã©ã¹ã³å ã«ãŠã2.1ïœã®ãã©ãã«ã ã¢ã«ããã
ïŒããªãªãã·ã¡ãã¬ã³ïŒã15mlã®æ°·é ¢é žäžã«æžæ¿
ãããïŒïœã®æ¿ç¡«é žã宀枩ã«ãŠããã¯ãããªãã
滎äžããããçãããã¯ãåŸããã«ã ã¢ã«ããã
éåäœã®50ã70ïŒ ã¯æº¶è§£ãããïŒè§£éåã¯ãã®æ··
åç©ã50ã60âã«30ã40åä¿æãããšå®çµã§ã
ããïŒãã®åŸã18mlã®æ°·é ¢é žäžã«2.3ïœïŒ18.5ããª
ã¢ã«ïŒã®ïŒâïŒâïŒïŒ3aβïŒïŒïŒ6aβâããã©ã
ããâ2Hâã·ã¯ããã³ãããïœããã©ã³âïŒâ
ãªã³ãåŒãã®ïŒâïŒååç©ãã溶ããã液ãã
ããã¯ãããªããã20ã25âã«ãŠäžèšæº¶æ¶²äžã«æ»Ž
äžããã管ãŸãã¯ãã©ã¹ã³ã¯å¯éããã枩床ã¯ïŒ
ãïŒæéã®ãã¡ã«70âãŸã§äžæããããã®æ··åç©
ã¯ãã®æž©åºŠã«ãŠã24ã30æéããã¯ããããŸãŸã«
ããŠããããããã枩床ã80âã«ãŸã§äžæããå
å¿æ··åç©ã¯ãã®æž©åºŠã«ãŠ20ã24æéããã¯ããç¶
ç¶ãããšãæ··åç©ã¯éçœãã€è²ã瀺ããå·åŽã
ãŠãæ··åç©ãé žæ§ãšãã也ããïŒïœã®é ¢é žãœãŒã
ãå ããããããããããé ¢é žã®å€§éšåãæžå§èž
çºïŒ15ãã«ã40ã50âïŒãããæ®ãã¯é ¢é žãšãã«
ïŒ20ã30mlïŒã«æº¶è§£ãã飜åçé žå¡©æº¶æ¶²ã§æ°åäž
æ§ã«ãªããŸã§æŽæµããæ°ŽæŽæµç©ã¯ïŒÃ15mlã®é ¢é ž
ãšãã«ã§æœåºãããå䜵ããé ¢é žãšãã«æº¶æ¶²ã¯ã
ïŒÃïŒc.c.ã®å¡©æ°Žã§æŽããç¡«é žãã°ãã·ãŠã ã§ä¹Ÿç¥
ãã溶å€ãé€ãã4.5ã4.8ïœã®åž¯é»ãã€è²ã®æ²¹ã
ãããããèå±€ã¯ãããã°ã©ã枬å®ã«ããã°ãã
ãããçæç©ã®90ïŒ ã¯åŒïœã®ã©ã¯ãã³ãžãªãŒã«
ãžã¢ã»ããŒãã§ããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aαâãããµ
ãããâïŒÎ²âã¢ã»ããã·ã¡ãã«â5aâã¢ã»ã
ãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒâ
ãªã³ãåŒïœã®ååç©ã å®æœäŸïŒã«è¿°ã¹ãããã«ããªã³ã¹åå¿ãè¡ãªã
ããçžéç¹ã¯ããã©ã¹ã³ãéããé ¢é žãœãŒãæ·»å
åŸãé ¢é žã®ååã ããèžçºããããããïŒãïŒml
ã®ç¡æ°Žé ¢é žãåå¿çæç©ã«å ããããããïŒæé
40ã50âã§ãããã¯ããç¶ããŠããèžçºãããæ®
ãã¯å®æœäŸïŒã«æºããŠä»äžããããžã¯ããã¡ã¿ã³
ãšé ¢é žãšãã«ïŒïŒïŒã®æ··åç©ãçšãã·ãªã«ã²ã«ã«
ã©ã ïŒ200ã250ïœïŒäžã§åŒïœã®ããããååç©
ã溶é¢ãããšã次ã®ç©çç¹æ§ãæãã3.8ãïŒïœ
ã®çæç©ãããããïŒ ãαãïŒ ïŒ€ïŒ57.6ã±0.5ãïŒïŒ£ïŒ0.93ãã¯ããããª
ã«ã ïŒ ïŒ²fïŒ0.53ïŒGF254 ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é ž
ãšãã«äœ¿çšïŒ f0.38ïŒäžèšæ¿äžã»ãã³ãŒã³âé ¢é žãšãã«
ïŒïŒïŒã®æ··åç©äœ¿çšïŒ fïŒ0.17ïŒäžèšæ¿äžã»ãã³ãŒã³âé ¢é žãšãã«
ïŒïŒïŒã®æ··åç©äœ¿çšïŒ fïŒ0.71ïŒäžèšæ¿äžã»é ¢é žãšãã«âã¡ã¿ããŒ
ã«ïŒïŒïŒã®æ··åç©äœ¿çšïŒ IRïŒÎœ maxïŒïŒ2950ïŒ1770ïŒ1740ïŒ1360ïŒ
1230ïŒ1160ïŒ1060ããã³1030âïŒcm NMRïŒC13ïŒïŒã«ãã³å ã«ã¯éå ±åã®çµæãšæ§
é ã®å²ä»ã瀺ãããŠããã 176.75ïŒãåŒãã©ã¯ãã³ïŒïŒ171.15ïŒâOOâïŒïŒ170.80ïŒâOOâïŒïŒ84.01ïŒïœïŒ
ãåŒãïŒïŒ76.95ïŒïœïŒ ãåŒãïŒïŒ63.96ïŒïœïŒâH2âOOCâ CH3ïŒïŒ51.35ïŒïœïŒãåŒãïŒïŒ40.57ïŒïœïŒ ãåŒãïŒïŒ38.10ïŒïœâH2âïŒïŒ35.74ïŒïœïŒïŒ£H2âïŒïŒ21.05ïŒïœïŒâH3ïŒããã³20.79ïŒïœïŒ
âH3ïŒã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã«ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³
âïŒâãªã³ïŒåŒïœã®ååç©ïŒ 15mlã®ã¡ã¿ããŒã«äžã«768mgïŒïŒããªã¢ã«ïŒã®
åŒïœ ã®ã©ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒãã溶ãã
ã液ã«0.6ã¢ã«ã®ãããªãŠã ãšããã·ãã®ã¡ã¿ã
ãŒã«æº¶æ¶²ïŒmlã宀枩ã«ãŠæ·»å ããããã®åå¿ã¯45
ã50åã§å®äºãããèå±€ã¯ãããã°ã©ãã€æž¬å®ã«
ããã°ã溶液ã¯é¡ç®ååç©ããããããå«ãã§ã
ãªãããã®åŸã§ã0.3ã0.5ïœã®é ¢é žãããã¯ãã
ãªãããåå¿æ··åç©ã«æ»Žäžãããã€ç空èžçºã«ãŠ
ã¡ã¿ããŒã«ãé€å»ãããæ®ããé ¢é žãšãã«ãšã¡ã¿
ããŒã«ãšã®ïŒïŒïŒã®æ··åç©10mläžã«æº¶è§£ãããã€
ãã®æº¶æ¶²ã12ã15ïœã®ã·ãªã«ã²ã«ãããªãã«ã©ã
ãééããããã«ã©ã ã¯ïŒïŒïŒã®é ¢é žãšãã«ïŒã¡
ã¿ããŒã«æ··åç©ã®80ã100mlã«ãŠæŽæµããããã©
ã¯ãã³ãžãªãŒã«ãžã¢ã»ããŒããããŸãããªã³ã¹å
å¿ããã®æ®åããåŒã®äžé£œåã©ã¯ãã³ã®æ ¹è·¡é
ãå«ããªãã°ã溶é¢æ¶²ã®æåã®ïŒã25mlã¯å¥ã«é
ããããã次ã®35ã80mlãŸã§ã®æº¶é¢æ¶²ã¯ãåŒïœ
ã®ååŠçã«çŽç²ãªååç©ãå«ãããã®çåãèžçº
ãããšã400ã500mgã®çæç©ããããããå¯èœãª
ãã以äžã®ç²Ÿè£œåã«ãçæç©ãå°éã®ã¢ã»ããã
ãªã«ã«æº¶è§£ãå°ãæ¿ããŸã§ãšãŒãã«ã§ããããã
ãšã奜ãŸãããå·èµåº«å ã«ä¿åãããšããã圢ã®
çµæ¶ãšããŠçŽç²ãªçæç©ãæ¶åºããã ç©çç¹æ§ïŒ èç¹ïŒ117.5ã118.5â ãαãïŒïŒ ïŒâ43.4ã±0.5ã
ïŒïŒ£ïŒ1.4ïŒã¡ã¿ããŒã«ïŒ fïŒ0.1ïŒGF254ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é žãš
ãã«äœ¿çšïŒ fïŒ0.35ïŒäžèšæ¿äžãé ¢é žãšãã«ãšã¡ã¿ããŒ
ã«ïŒïŒïŒã®æ··åç©äœ¿çšïŒ IRïŒÎœ maxïŒïŒ3350ïŒ2900ïŒ1755ïŒ1070ãã
ã³1030cm-1 ãã®çæç©ã¯ä»ã®æ¹æ³ã§èª¿è£œãããçæ£ã®è©Šæ
ãšåäžã§ããããšã蚌æãããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã¡ãã«âïŒÎ±âãã
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³ïŒåŒïœã®ååç©ïŒ 15mlã¡ã¿ããŒã«äžã«åŒIcã®ã©ã¯ãã³ãžãªãŒã«ãž
ã¢ã»ããŒãã®910mgã»ïŒ3.58ã¢ã«ïŒã溶ããã液ã«
察ããïŒmlã®ã¡ã¿ããŒã«äžã®50mgã®ïœâãã«ãšã³
ã¹ã«ããªã³é žã溶ããã液ãæ·»å ãããã€åå¿æ··
åç©ã68ã72âã®æ¹¯æµŽäžã®èžçã³ã³ãã³ãµãŒä»ã®
ãã©ã¹ã³å ã§ããã¯ããã圢æããé ¢é žã¡ãã«ã
çåºããããåå¿ã¯ãçŽïŒã10æéããã€ãŠé ¢é ž
ã¡ãã«ïŒã¡ã¿ããŒã«æ··åç©ãçŽïŒãïŒmlçåºãã
ãåŸãå®äºããã湯济ã®æž©åºŠãé«ããããã«ã¡ã¿
ããŒã«ïŒãïŒmlãçåºããããªãæ®çããã¡ã¿ã
ãŒã«ã¯ãã³ãŒã³ãšã®å ±æ²žèžçã«ãã€ãŠé€å»ããã
ïŒå ±æ²žæ··åç©ã®æ²žç¹ïŒ56âïŒãã³ãŒã³ã¯æžå§èžçº
ããçæç©ã¯ãåå®æœäŸã©ãããã«ã©ã ã¯ããã
ã°ã©ãã€ã§ç²Ÿè£œãããé¡èšååç©ã¯570ã580mgã
ããããããããçæç©ã®ç©çç¹æ§ã¯å®æœäŸïŒã®
ååç©ã®ãããšçããã å®æœäŸ ïŒ ïŒâïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aαâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«â5aâã¢ã»
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³ïŒåŒïœã®ååç©ïŒ åŒïœã®ã©ã¯ãã³ã»ãžãªãŒã«ã»ãžã¢ã»ããŒã
600mgïŒ2.36ããªã¢ã«ïŒã15mlã®ã¡ã¿ããŒã«ã«æº¶
ãããã液ã«ãã¡ã¿ããŒã«ïŒmläžã«40mgã®ïœâã
ã«ãšã³ã¹ã«ãã³é žã溶ããã液ãå ããåå¿æ··å
ç©ã¯å®€æž©ã«ãŠïŒã10æéããã¯ããããåå¿ã¯è
å±€ã¯ãããã°ã©ãã€ã«ããå¶åŸ¡ãããã GF254ã·ãªã«ã²ã«âéŒæ¿äžã«æ€åºãããæ··åäž
åäž»çæç©ã®ïŒ²fïŒã¬ãŒãã»ãã¢ã¯ã¿ãŒïŒå€ã¯æ¬¡
ã®ãšããã§ããïŒ ãè¡šã åå¿å®çµåŸãæ··åç©ã¯å®æœäŸïŒã«è¿°ã¹ãããã«
ä»äžãããããããããéé»è²æ²¹ã¯æº¶é¢å€ãšããŠ
é ¢é žãšãã«ïŒã¡ã¿ããŒã«ãçšãã50ã100å容é
ã®ã·ãªã«ã²ã«ã«ã©ã äžã§ã¯ãããã°ã©ãã€ã«ã
ããåºã ã«ã¡ã¿ããŒã«æ¿åºŠãïŒïŒïŒã®å²åãã
ïŒïŒïŒãŸã§å¢å ãããçåã¯èå±€ã¯ãããã°ã©ã
ã€æž¬å®ãè¡ãªããåäžçæç©ãå«ãçåã¯ãŸãšã
ãŠãèžçºãããããããŠãåŒIaã®ã©ã¯ãã³ãžãªãŒ
ã«ã¢ãã¢ã»ããŒãã310mgïŒ62ïŒ ïŒããããã å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããã·ã¡ãã«âïŒÎ±âãã
ããã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³âïŒ
âãªã³âãã«ã ã¢ã«ãããã¢ã»ã¿ãŒã«ãïŒR5ãš
R6ãæ°ŽçŽ ã§ããïŒè¬åŒIxã®ååç©ïŒ ïŒïœã»ïŒ5.88ããªã¢ã«ïŒã®IdåŒã®ã©ã¯ãã³ãžãª
ãŒã«ãšïŒïœã»ã®ãã©ãã«ã ã¢ã«ããããšãã20ml
ã®ãã³ãŒã³äžã§æ¯ãšããããããããæ°æ»Žã®äžã
ãåããŠçŽ ãšãŒãã«ååç©ãå ããããããã©ã¹
ã³ãéãã宀枩ã«ãŠïŒæ¥éæŸçœ®ãããïŒæ¥åŸãå
å¿æ··åç©ãããªãšãã«ã¢ãã³ã§äžåããæ²æ®¿ãã
å¡©ãå¥ãã溶å€ãèžçºããæ®çæ²¹ã¯ãšãŒãã«ïŒ
ãããµã³æ··åç©ããåçµæ¶ãããé¡ç®ååç©ãã
ãããã fïŒ0.37ïŒé ¢é žãšãã«ïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœãã©ã³â
ïŒâãªã³âãã³ãºã¢ã«ãããâã¢ã»ã¿ãŒã«
ïŒR5ãããšãã«åºã§R6ãæ°ŽçŽ ã§ããäžè¬åŒïœ
ã®ååç©ïŒ ïŒmlã®ãã³ãŒã³äžã«722mgïŒ2.71ããªã¢ã«ïŒã®
åŒIeã®ã©ã»ãäœãžãªãŒã«ãžã¢ã»ããŒãã溶ããã
液ã«å¯ŸãïŒmlã®ãã³ãŒã³äžã«ãã³ãºã¢ã«ããããž
ã¢ã»ã¿ãŒã«ã溶ããã液ãæ··åãããã®åå¿æ··å
ç©ã«0.2mlã®ã¡ã¿ããŒã«ã«æ¿ç¡«é žïŒmgã溶ããã
液ãå ãããåå¿æ··åç©ã¯15ã20æéå ç±ããã
é ¢é žã¡ãã«ã¯é£ç¶çã«çåºããããåå¿å®çµæã«
ã¯ãæ··åç©ã¯ããªãšãã«ã¢ãã³ã§äžåããæ²æ®¿ã
ãå¡©ãå¥ãã液ã¯èžçºãããæ®çç©ã¯ç¡æ°Žãš
ãŒãã«10mläžã«æº¶è§£ããç³æ²¹ãšãŒãã«ãæ·»å ããŠ
çµæ¶åãããé¡ç®ååç©ãããããã f0.51ïŒé ¢é žãšãã«ïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβâãããµ
ãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±âã
ãããªãã·â2Hâã·ã¯ããã³ã¿ãïœããã©ã³
âïŒâãªã³âã¢ã»ãã³ã¢ã»ã¿ãŒã«ïŒR5ïŒR6ã
ã¡ãã«ã§ãããäžè¬åŒïœã®ååç©ïŒ 10mlã®ãã³ãŒã³äžã®åŒIdã®ã©ã¯ãã³ãžãªãŒã«ã®
102mgã»ïŒ0.56ããªã¢ã«ïŒã«å¯ŸããŠãïŒmlã®ïŒïŒïŒ
âãžã¡ãããªãã·âãããã³ïŒã¢ã»ãã³ãžã¡ãã«
ã¢ã»ã¿ãŒã«ïŒããã³25mgã»ã®ïœâãã«ãšã³âã¹ã«
ããªã³é žïŒæ°Žåç©ãå ãããããåå¿æ··åç©ã¯ã
å ±æ²žæ··åç©ãçåºé€å»ããããã«75ã80âã«ä¿æ
ãããããã¢ã»ãã³ïŒãžã¡ãã«ã¢ã»ã¿ãŒã«ã¯æ»ã
ãããïŒã10æéåŸãåå¿ã¯å®çµãããåå¿æ··å
ç©ãèžçºãããšãæèµ€è²æ²¹ããããããããïŒml
ã®ãšãŒãã«ã«æº¶ãããããããïŒmlã®ç³æ²¹ãšãŒã
ã«ãå ããŠçµæ¶åããã57mgã®é¡èšååç©ããã
ããã fïŒ0.50ïŒGF254ã·ãªã«ã²ã«âéŒæ¿äžãé ¢é žãš
ãã«äœ¿çšïŒ å®æœäŸ ïŒ ïŒÂ±ïŒâïŒïŒ3aβïŒïŒïŒïŒïŒïŒïŒ6aβïŒïŒâã
ããµãããâïŒÎ²âããããªãã·ã¡ãã«âïŒÎ±
âããããªãã·â2Hâã·ã¯ããã³ã¿ãïœãã
ã©ã³âïŒâãªã³âïŒåŒIdã®ååç©ïŒ ïŒmlã®36ã38ïŒ ãã«ã ã¢ã«ããã溶液ã«å¯Ÿã
ãŠãïŒmlã®æ¿ç¡«é žãå°ããã€å·åŽãããã¯ãããª
ããæ·»å ãããã®æ··åç©ã«ïŒïœïŒ8.0ããªã¢ã«ïŒ
ã®ïŒÂ±ïŒâïŒïŒ3aβïŒ6.6aβâããã©ãããâ
2Hâã·ã¯ããã³ã¿ããïœããã©ã³âïŒâãªã³ã
å ãããåå¿æ··åç©ãå«ããã©ã¹ã³ãéãã70â
ã«70ã80æéä¿æããããããã垯é»ãã€è²æ²¹ç¶
ç©è³ªãããã©ã¹ã³éæŸåŸãïŒïœã®çé žãœãŒãäžã«
泚ããæžæ¿ç©ã¯å®å šã«é ¢é žãšãã«ã«ãã€ãŠæœåºã
ããå䜵ããé ¢é žãšãã«æœåºç©ã¯å¡©æ°ŽæŽæµãç¡«é ž
ãããªãŠã äžã®ä¹Ÿç¥ããåŸãé ¢é žãšãã«ã¯èžçºã
ããæ®çé»è²æ²¹ã¯äž»æåãšããŠã®åŒIdã§ç€ºããã
ã©ã¯ãã³ãžãªãŒã«ãšãããã³ïŒ²ãæ°ŽçŽ ã瀺ãåŒ
ã®ååç©äžŠã³ã«æ°çš®ã®æªç¢ºèªç©è³ªããæã€ãŠã
ããåŒïœã®ååç©ã¯å®æœäŸïŒã«ã®ã¹ãããã«ã
ã«ã©ã ã¯ãããã°ã©ãã€ã§åé¢ããããåŒïœã®
ããããã©ã»ãäœååç©ã®ç©çæ§ç¶ã¯èç¹ãé€ã
ãŠã¯ãå®æœäŸïŒã«ãŠããããïŒâïŒâå·Šå³ç·ãžãª
ã«ã®æ§ç¶ãšåçã§ãããã©ã»ãäœçæç©ã®èç¹ã¯
91ã92âã§ããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ äžè¬åŒ ãåŒäžãR5ããã³R6ã¯æ°ŽçŽ ãã¡ãã«åºããã³
ããšãã«åºããéžæãããR5ããã³R6ã®ããã
ãäžã€ãããšãã«åºã§ããå Žåã¯ãã®ä»ã®äžã€ã¯
æ°ŽçŽ ã瀺ãã ã§ç€ºãããã©ã¯ãã³ãžãªãŒã«èªå°äœã ïŒ ãã®å³æããã³å·Šæ察æäœã§ããããšãç¹åŸŽ
ãšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®èªå°äœã ïŒ äžè¬åŒ ãåŒäžãR5ããã³R6ã¯æ°ŽçŽ ãã¡ãã«åºããã³
ããšãã«åºããéžæãããR5ããã³R6ã®ããã
ãäžã€ãããšãã«åºã§ããå Žåã¯ãã®ä»ã®äžã€ã¯
æ°ŽçŽ ã瀺ãã ã§ç€ºãããå åŠæŽ»æ§åãŸãã¯ã©ã»ãåã©ã¯ãã³ãž
ãªãŒã«èªå°äœã®åææ¹æ³ã§ãã€ãŠã äžè¬åŒ ã§ç€ºãããã©ã»ãåãŸãã¯å åŠæŽ»æ§åã©ã¯ãã³
ããåŒ·é žãšæ°Žã®æ··åç©ããŸãã¯ä»»æã«ïŒåãïŒå
ãããã¯ïŒåã®ããã²ã³ååã«ãã€ãŠçœ®æãããŠ
ããŠãããäœçŽã¢ã«ã«ã³ã«ã«ãã³é žã®ååšäžã§ã
ã«ã ã¢ã«ããããŸãã¯ãã«ã ã¢ã«ãããéåäœãš
åå¿ãããŠäžè¬åŒ ãåŒäžãR3ããã³R4ã¯åçš®ãŸãã¯ç°çš®ã§ãã€
ãŠããã€æ°ŽçŽ ã§ãããããŸãã¯ä»»æã«ïŒåãïŒå
ãããã¯ïŒåã®ããã²ã³ååã«ãã眮æãããŠã
ãŠãããäœçŽã¢ã«ã«ãã€ã«åºã瀺ãã ã§ç€ºãããååç©ãåŸã次ãã§å¿ èŠã«å¿ããŠè©²å
åç©ïŒïŒãé žæ§ãããã¯ã¢ã«ã«ãªæ§åªäœäžã§éš
åå æ°Žå解ãå šå æ°Žå解ãããã¯ã¢ã«ã³ãŒãªã·ã¹
ã®ããããã«ãããåŸã該ååç©ïŒïŒãäžè¬åŒ
R5âCHOãããã¯R5âCOâR6ïŒåŒäžãR5ãã
ã³R6ã¯åèšãããšåäžã§ããïŒã§ç€ºãããåå
ç©ãŸãã¯ãããã®ååç©ã®ã¢ã»ã¿ãŒã«é¡ãšåå¿ã
ããããšããæãæ¹æ³ã ïŒ äœçŽã¢ã«ã«ã³ã«ã«ãã³é žãšããŠã®é ¢é žãå«ã
åå¿åªäœäžã§åå¿ãããŠãR3ããã³ïŒãŸãã¯R4
ãã¢ã»ãã«åºãè¡šããäžè¬åŒïŒïŒã§ç€ºãããå
åç©ãåæããããšãç¹åŸŽãšããç¹èš±è«æ±ã®ç¯å²
第ïŒé èšèŒã®æ¹æ³ã ïŒ åŒ·é žãšããŠç¡«é žããªã³é žãŸãã¯äžããåããŠ
çŽ ã»ãšãŒãã«é¯äœã䜿çšããããšãç¹åŸŽãšããç¹
èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ ä»»æã«ïŒåãïŒåãŸãã¯ïŒåã®ããã²ã³åå
ã«ãã眮æãããŠããŠãããäœçŽã¢ã«ã«ã³ã«ã«ã
ã³é žã®ååšäžã§ãäžè¬åŒïŒïŒã®ã©ã¯ãã³ãšãã«
ã ã¢ã«ããããšãåå¿ãããŠäžè¬åŒïŒïŒã®åå
ç©ïŒåŒäžãR3ãšR4ã¯ïŒåãïŒåãŸãã¯ïŒåã®ã
ãã²ã³ååã«ãã眮æãããŠããŠãããäœçŽã¢ã«
ã«ãã€ã«åºã瀺ãïŒãåæããããšãç¹åŸŽãšãã
ç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ åŸãããäžè¬åŒïŒïŒã®ååç©ïŒåŒäžãR3
ããã³ïŒãŸãã¯R4ã¯æ°ŽçŽ 以å€ã®ãã®ã瀺ãïŒã
é žæ§ãããã¯ã¢ã«ã«ãªæ§åªäœäžã§å æ°Žå解ãŸãã¯
ã¢ã«ã³ãŒãªã·ã¹ã«ãããŠäžè¬åŒïŒïŒã®ååç©
ïŒåŒäžãR3ãšR4ã¯æ°ŽçŽ ã瀺ãïŒãåæããããšã
ç¹åŸŽãšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ åŸãããäžè¬åŒïŒïŒã®ååç©ïŒåŒäžãR3
ããã³R4ã¯æ°ŽçŽ 以å€ã®ãã®ã瀺ãïŒãé žæ§ãã
ãã¯ã¢ã«ã«ãªæ§åªäœäžã§éšåå æ°Žå解ãŸãã¯ã¢ã«
ã³ãŒãªã·ã¹ã«ãããããšã«ãããäžè¬åŒïŒïŒã®
ååç©ïŒåŒäžãR3ããã³R4ã®ãã¡ã®äžã€ã¯æ°ŽçŽ
ã§ãããä»ã®äžã€ã¯ä»»æã«ïŒåãïŒåãŸãã¯ïŒå
ã®ããã²ã³ååã«ãã眮æãããŠããŠãããäœçŽ
ã¢ã«ã«ãã€ã«åºã瀺ãïŒãåæããããšãç¹åŸŽãš
ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒ åŸãããäžè¬åŒïŒïŒã®ååç©ïŒåŒäžãR3
ããã³R4ã¯æ°ŽçŽ 以å€ã®ãã®ã瀺ãïŒãäžè¬åŒR5
âCHOãããã¯R5âCOâR6ïŒåŒäžãR5ããã³
R6ã¯äžèšãããšåäžã§ããïŒã§ç€ºããããªããœ
ååç©ãšåå¿ããããããŸãã¯ãããã®ãªããœå
åç©ã®ã¢ã»ã¿ãŒã«é¡ãšåå¿ãããŠäžè¬åŒïŒïŒã§
瀺ãããã©ã¯ãã³ãžãªãŒã«èªå°äœïŒåŒäžãR5ã
ãã³R6ã¯äžèšãããšåäžã§ããïŒãåæããã
ãšãç¹åŸŽãšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹
æ³ã ïŒïŒ åŸãããäžè¬åŒïŒïŒã§ç€ºãããååç©
ïŒåŒäžãR3ããã³R4ã¯æ°ŽçŽ ã瀺ãïŒãäžè¬åŒR5â
CHOãããã¯R5âCOâR6ã§ç€ºããããªããœåå
ç©ïŒåŒäžãR5ããã³R6ã¯åèšãããšåäžã§ã
ãïŒåå¿ããããããŸãã¯ãããã®ãªããœååç©
ã®ã¢ã»ã¿ãŒã«é¡ãšåå¿ãããŠãäžè¬åŒïŒïŒã§ç€º
ãããã©ã¯ãã³ãžãªãŒã«èªå°äœïŒåŒäžãR5ãã
ã³R6ã¯åèšãããšåäžã§ããïŒãåæããããš
ãç¹åŸŽãšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã ïŒïŒ äžè¬åŒïŒïŒã§ç€ºãããäºç°ã©ã¯ãã³ãç¡«
é žã®ååšäžã§ãã«ã ã¢ã«ããã氎溶液ãšåå¿ãã
ãŠãäžè¬åŒïŒïŒã§ç€ºãããååç©ïŒåŒäžãR3
ããã³R4ã¯æ°ŽçŽ ã瀺ãïŒãåæããããšãç¹åŸŽ
ãšããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®æ¹æ³ã
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU76CI1644A HU173711B (hu) | 1976-02-20 | 1976-02-20 | Sposob poluchenija biciklicheskikh proizvodnykh laktonov ispol'zuemykh intermediarnymi soedineijami v sinteze prostaglandinov |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS52105163A JPS52105163A (en) | 1977-09-03 |
| JPS6143353B2 true JPS6143353B2 (ja) | 1986-09-26 |
Family
ID=10994602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1799277A Granted JPS52105163A (en) | 1976-02-20 | 1977-02-21 | Novel bicyclic lactone utilized as synthetic intermediate of prostaglandine and preparation thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4126622A (ja) |
| JP (1) | JPS52105163A (ja) |
| CA (1) | CA1116175A (ja) |
| CH (1) | CH619944A5 (ja) |
| FI (1) | FI69073C (ja) |
| GB (1) | GB1566510A (ja) |
| HU (1) | HU173711B (ja) |
| SE (1) | SE435282B (ja) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0610041Y2 (ja) * | 1987-08-31 | 1994-03-16 | åœç£éå±å·¥æ¥æ ªåŒäŒç€Ÿ | èªåè»çšã¢ãŠããã¢ãã³ãã« |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0249953A1 (en) * | 1986-06-19 | 1987-12-23 | Nissan Chemical Industries Ltd. | Optically active bicyclo carboxylic acids and their derivatives |
| JP3097145B2 (ja) * | 1991-02-27 | 2000-10-10 | æ¥ç£ååŠå·¥æ¥æ ªåŒäŒç€Ÿ | ã³ãŒãªãŒã©ã¯ãã³ãžãªãŒã«ã®å åŠåå²æ¹æ³ |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1353922A (en) * | 1971-04-13 | 1974-05-22 | Ici Ltd | Bicycloheptene derivatives |
-
1976
- 1976-02-20 HU HU76CI1644A patent/HU173711B/hu not_active IP Right Cessation
-
1977
- 1977-02-15 SE SE7701666A patent/SE435282B/xx not_active IP Right Cessation
- 1977-02-18 CA CA272,051A patent/CA1116175A/en not_active Expired
- 1977-02-18 FI FI770531A patent/FI69073C/fi not_active IP Right Cessation
- 1977-02-18 GB GB6977/77A patent/GB1566510A/en not_active Expired
- 1977-02-21 CH CH213877A patent/CH619944A5/fr not_active IP Right Cessation
- 1977-02-21 JP JP1799277A patent/JPS52105163A/ja active Granted
- 1977-02-22 US US05/770,998 patent/US4126622A/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0610041Y2 (ja) * | 1987-08-31 | 1994-03-16 | åœç£éå±å·¥æ¥æ ªåŒäŒç€Ÿ | èªåè»çšã¢ãŠããã¢ãã³ãã« |
Also Published As
| Publication number | Publication date |
|---|---|
| FI69073C (fi) | 1985-12-10 |
| US4126622A (en) | 1978-11-21 |
| FI69073B (fi) | 1985-08-30 |
| CA1116175A (en) | 1982-01-12 |
| SE435282B (sv) | 1984-09-17 |
| JPS52105163A (en) | 1977-09-03 |
| SE7701666L (sv) | 1977-08-21 |
| CH619944A5 (ja) | 1980-10-31 |
| GB1566510A (en) | 1980-04-30 |
| FI770531A (ja) | 1977-08-21 |
| HU173711B (hu) | 1979-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20070123719A1 (en) | Synthesis of cannabinoids | |
| EP0045118A2 (en) | Intermediates for the synthesis of bicyclo (2,2,1) heptanes and bicyclo (2,2,1) hept-2Z-enes | |
| Rosenquist et al. | Synthesis of enantiomerically pure trans-3, 4-substituted cyclopentanols by enzymatic resolution | |
| Bartels et al. | A selectivity study of activated ketal reduction with borane dimethyl sulfide | |
| Davies et al. | Rhodium carbenoid mediated cyclisations. Part 4. Synthetic approaches to oxepanes related to zoapatanol | |
| JPS6143353B2 (ja) | ||
| JPS609035B2 (ja) | ãã·ã¯ããªã¯ã¿ã³èªå°äœã®è£œé æ³ | |
| KR0144684B1 (ko) | ë칎륎복ì€ì°ì ëªšë žìì€í 륎 ë° ê·žì ì ì¡°ë°©ë² | |
| US4024181A (en) | Analogues of prostanoic acids | |
| Berens et al. | The First Stereoselective Synthesis of Racemic. beta.-Multistriatin: A Pheromone Component of the European Elm Bark Beetle Scolytus multistriatus (Marsh.) | |
| US4204999A (en) | Process for making bicyclic lactone derivatives for use as intermediates in the synthesis of prostaglandins | |
| CA2000179C (en) | Cyclopenteneheptenoic acid derivatives and method of preparation thereof | |
| TW201945332A (zh) | 補åäŒæŽååçŽ ä¹æ¹æ³ | |
| KR940006631B1 (ko) | íë¡ì€íêžëëì ì 구첎 ë° ê·žì ì ì¡°ë°©ë² | |
| JPH0314030B2 (ja) | ||
| US4137244A (en) | Asymmetric synthesis of optically active prostaglandins | |
| US5216177A (en) | Method of preparing trans-3,4-disubstituted-γ-lactones | |
| CN114341098B (zh) | ç¯æç·ååç©çå¶å€æ¹æ³ãå é ¯ååç©çå¶å€æ¹æ³ãäºéååç©çå¶å€æ¹æ³åååç© | |
| US4021425A (en) | Process for producing enone intermediates | |
| CA1254577A (en) | 7-oxabicycloheptane prostaglandin intermediates and method for preparing same | |
| EP0432021A1 (fr) | Nouveaux intermédiaires, leur procédé de préparation et leur utilisation pour la synthÚse des vitamines A et E | |
| Prakash et al. | Synthesis of the major urinary metabolite of prostaglandin D 2 | |
| FI80028C (fi) | Foerfarande foer framstaellning av alfa- substituerade alkylarylketaler. | |
| JPH03123780A (ja) | ïŒïŒšâãã³ãŸïŒ»ïœïŒœãããªãžã³èªå°äœ | |
| KR810001248B1 (ko) | ìíŽë¡ííì¬ì ëœí€ì ë첎ì ì ì¡°ë°©ë² |