DE2337343A1 - Porstancarbonsaeure- und prostencarbonsaeurederivate, zwischenprodukte und verfahren zur herstellung von biologisch wichtigen verbindungen der prostaglandinart - Google Patents
Porstancarbonsaeure- und prostencarbonsaeurederivate, zwischenprodukte und verfahren zur herstellung von biologisch wichtigen verbindungen der prostaglandinartInfo
- Publication number
- DE2337343A1 DE2337343A1 DE19732337343 DE2337343A DE2337343A1 DE 2337343 A1 DE2337343 A1 DE 2337343A1 DE 19732337343 DE19732337343 DE 19732337343 DE 2337343 A DE2337343 A DE 2337343A DE 2337343 A1 DE2337343 A1 DE 2337343A1
- Authority
- DE
- Germany
- Prior art keywords
- carbon atoms
- trans
- group
- hydroxy
- straight
- 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.)
- Ceased
Links
- 239000002253 acid Substances 0.000 title claims description 419
- 150000001875 compounds Chemical class 0.000 title claims description 169
- 238000000034 method Methods 0.000 title claims description 121
- 238000002360 preparation method Methods 0.000 title claims description 90
- 230000008569 process Effects 0.000 title claims description 36
- 239000000543 intermediate Substances 0.000 title description 26
- 150000003180 prostaglandins Chemical class 0.000 title description 15
- -1 4-tetrahydropyranyloxycyclopentenone tetrahydropyranyl ester Chemical class 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 181
- 125000004432 carbon atom Chemical group C* 0.000 claims description 177
- 239000000203 mixture Substances 0.000 claims description 157
- 239000000047 product Substances 0.000 claims description 97
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 150000002148 esters Chemical class 0.000 claims description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 229910052744 lithium Inorganic materials 0.000 claims description 40
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 35
- 239000007818 Grignard reagent Substances 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 239000011777 magnesium Substances 0.000 claims description 28
- 150000004795 grignard reagents Chemical class 0.000 claims description 27
- 230000003287 optical effect Effects 0.000 claims description 25
- DHNDDRBMUVFQIZ-UHFFFAOYSA-N 4-hydroxycyclopent-2-en-1-one Chemical compound OC1CC(=O)C=C1 DHNDDRBMUVFQIZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000005977 Ethylene Substances 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 230000002829 reductive effect Effects 0.000 claims description 19
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 19
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 18
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 150000001735 carboxylic acids Chemical class 0.000 claims description 12
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 11
- 235000015243 ice cream Nutrition 0.000 claims description 11
- 239000012442 inert solvent Substances 0.000 claims description 10
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000002091 cationic group Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 5
- UKSFURGLGLVJNV-UHFFFAOYSA-M copper(1+);tributylphosphane;iodide Chemical compound I[Cu].CCCCP(CCCC)CCCC UKSFURGLGLVJNV-UHFFFAOYSA-M 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 4
- 150000001457 metallic cations Chemical class 0.000 claims description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 4
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 4
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 239000011981 lindlar catalyst Substances 0.000 claims description 3
- 229940005561 1,4-benzoquinone Drugs 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims 1
- 150000001261 hydroxy acids Chemical class 0.000 claims 1
- ZGSXEXBYLJIOGF-BOPNQXPFSA-N iwr-1 Chemical compound C=1C=CC2=CC=CN=C2C=1NC(=O)C(C=C1)=CC=C1N1C(=O)[C@@H]2C(C=C3)CC3[C@@H]2C1=O ZGSXEXBYLJIOGF-BOPNQXPFSA-N 0.000 claims 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 399
- 239000000243 solution Substances 0.000 description 221
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 159
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 151
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 117
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
- 239000003921 oil Substances 0.000 description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 63
- 238000004519 manufacturing process Methods 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000012298 atmosphere Substances 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000004215 Carbon black (E152) Substances 0.000 description 23
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000000284 extract Substances 0.000 description 23
- 229930195733 hydrocarbon Natural products 0.000 description 23
- 150000002430 hydrocarbons Chemical class 0.000 description 23
- 125000006239 protecting group Chemical group 0.000 description 23
- 239000002904 solvent Substances 0.000 description 22
- 229910052749 magnesium Inorganic materials 0.000 description 21
- 229940091250 magnesium supplement Drugs 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 125000005907 alkyl ester group Chemical group 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 229960000583 acetic acid Drugs 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- 235000001055 magnesium Nutrition 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 150000004702 methyl esters Chemical class 0.000 description 16
- 210000002307 prostate Anatomy 0.000 description 16
- 238000007127 saponification reaction Methods 0.000 description 16
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 16
- 239000000463 material Substances 0.000 description 15
- 210000002784 stomach Anatomy 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 13
- 125000004429 atom Chemical group 0.000 description 13
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 13
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 229910052794 bromium Chemical group 0.000 description 12
- 238000004821 distillation Methods 0.000 description 12
- LFBXOVKARKTQRF-UHFFFAOYSA-N ethyl 6-(5-oxocyclopenten-1-yl)hexanoate Chemical compound CCOC(=O)CCCCCC1=CCCC1=O LFBXOVKARKTQRF-UHFFFAOYSA-N 0.000 description 12
- 229910052740 iodine Inorganic materials 0.000 description 12
- 229910001641 magnesium iodide Inorganic materials 0.000 description 12
- 229910000033 sodium borohydride Inorganic materials 0.000 description 12
- 239000012279 sodium borohydride Substances 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- FXZYALYTAQTZQB-QURGRASLSA-N [[(e)-1-bromooct-1-en-3-yl]oxy-diphenylmethyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC(CCCCC)\C=C\Br)C1=CC=CC=C1 FXZYALYTAQTZQB-QURGRASLSA-N 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- JFNYLACZZRWLJV-UHFFFAOYSA-N ethyl 2-[4-(5-oxocyclopenten-1-yl)butoxy]acetate Chemical compound CCOC(=O)COCCCCC1=CCCC1=O JFNYLACZZRWLJV-UHFFFAOYSA-N 0.000 description 11
- 239000011630 iodine Substances 0.000 description 11
- JWZKZFQTVYBYTO-UHFFFAOYSA-N lithium;[oct-1-en-3-yloxy(diphenyl)methyl]benzene Chemical compound [Li+].C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC(CCCCC)C=[CH-])C1=CC=CC=C1 JWZKZFQTVYBYTO-UHFFFAOYSA-N 0.000 description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- 229920002261 Corn starch Polymers 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 239000008120 corn starch Substances 0.000 description 10
- BQQKMCMOJHBTAI-UHFFFAOYSA-N ethyl 2-ethyl-7-(5-oxocyclopenten-1-yl)heptanoate Chemical class CCOC(=O)C(CC)CCCCCC1=CCCC1=O BQQKMCMOJHBTAI-UHFFFAOYSA-N 0.000 description 10
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 10
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 208000025865 Ulcer Diseases 0.000 description 9
- NZHXEWZGTQSYJM-UHFFFAOYSA-N [bromo(diphenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 NZHXEWZGTQSYJM-UHFFFAOYSA-N 0.000 description 9
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 9
- CDSGJHCARATGKG-UHFFFAOYSA-N bis(3-methylbutyl)borane Chemical compound CC(C)CCBCCC(C)C CDSGJHCARATGKG-UHFFFAOYSA-N 0.000 description 9
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 9
- ZBNBPUJUZFQCPY-UHFFFAOYSA-N ethyl 2-fluoro-7-(5-oxocyclopenten-1-yl)heptanoate Chemical compound CCOC(=O)C(F)CCCCCC1=CCCC1=O ZBNBPUJUZFQCPY-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 150000001925 cycloalkenes Chemical class 0.000 description 8
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 8
- OXWBFQQAUHFTHT-UHFFFAOYSA-N ethyl 7-(5-oxocyclopenten-1-yl)heptanoate Chemical compound CCOC(=O)CCCCCCC1=CCCC1=O OXWBFQQAUHFTHT-UHFFFAOYSA-N 0.000 description 8
- USKWBGXLPIRQMT-UHFFFAOYSA-N ethyl 9-(5-oxocyclopenten-1-yl)nonanoate Chemical compound CCOC(=O)CCCCCCCCC1=CCCC1=O USKWBGXLPIRQMT-UHFFFAOYSA-N 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000012258 stirred mixture Substances 0.000 description 8
- 231100000397 ulcer Toxicity 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- ITZFMOHXACVXAX-UHFFFAOYSA-N [oct-1-yn-3-yloxy(diphenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OC(CCCCC)C#C)C1=CC=CC=C1 ITZFMOHXACVXAX-UHFFFAOYSA-N 0.000 description 7
- UQDAEORWFCPQCU-UHFFFAOYSA-N acetic acid;oxolane;hydrate Chemical compound O.CC(O)=O.C1CCOC1 UQDAEORWFCPQCU-UHFFFAOYSA-N 0.000 description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 7
- WNEVWRVCGATGGE-UHFFFAOYSA-N ethyl 2-methyl-7-(5-oxocyclopenten-1-yl)heptanoate Chemical compound CCOC(=O)C(C)CCCCCC1=CCCC1=O WNEVWRVCGATGGE-UHFFFAOYSA-N 0.000 description 7
- VXPGNJGVAQGTFR-UHFFFAOYSA-N ethyl 7-(5-oxocyclopenten-1-yl)-2-phenylheptanoate Chemical compound C=1C=CC=CC=1C(C(=O)OCC)CCCCCC1=CCCC1=O VXPGNJGVAQGTFR-UHFFFAOYSA-N 0.000 description 7
- 150000004820 halides Chemical class 0.000 description 7
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 description 7
- LJGZTKUPHNSUFB-DAXSKMNVSA-N methyl (z)-7-(5-oxocyclopenten-1-yl)hept-6-enoate Chemical compound COC(=O)CCCC\C=C/C1=CCCC1=O LJGZTKUPHNSUFB-DAXSKMNVSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 7
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- JGHYBJVUQGTEEB-UHFFFAOYSA-M dimethylalumanylium;chloride Chemical compound C[Al](C)Cl JGHYBJVUQGTEEB-UHFFFAOYSA-M 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
- PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
- FWEIRECJUNSXMA-UHFFFAOYSA-N ethyl 2-[4-(3-bromo-5-oxocyclopenten-1-yl)butoxy]acetate Chemical compound CCOC(=O)COCCCCC1=CC(Br)CC1=O FWEIRECJUNSXMA-UHFFFAOYSA-N 0.000 description 1
- RWGKIJDXSDWGGS-LJJQOFDWSA-N ethyl 2-[4-[(1R,2S)-2-(3-hydroxyoctyl)-5-oxocyclopentyl]butoxy]acetate Chemical compound CCCCCC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCOCC(=O)OCC RWGKIJDXSDWGGS-LJJQOFDWSA-N 0.000 description 1
- YDWUNRWZQFGIMR-LJJQOFDWSA-N ethyl 2-[4-[(1R,2S)-2-(3-hydroxyoctyl)-5-oxocyclopentyl]butylsulfanyl]acetate Chemical compound CCCCCC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCSCC(=O)OCC YDWUNRWZQFGIMR-LJJQOFDWSA-N 0.000 description 1
- VMDIQJCBAIUJGY-UHFFFAOYSA-N ethyl 2-ethyl-7-(3-hydroxy-5-oxocyclopenten-1-yl)heptanoate Chemical compound CCOC(=O)C(CC)CCCCCC1=CC(O)CC1=O VMDIQJCBAIUJGY-UHFFFAOYSA-N 0.000 description 1
- REHADBNZSWMPGF-OEXSPLCWSA-N ethyl 2-ethyl-7-[(1R,2S)-2-(3-hydroxyoct-4-ynyl)-5-oxocyclopentyl]heptanoate Chemical compound CCCC#CC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCCC(CC)C(=O)OCC REHADBNZSWMPGF-OEXSPLCWSA-N 0.000 description 1
- GBGIDJVCWZHVAL-LHQJTOJGSA-N ethyl 2-fluoro-7-[(1R,2S)-2-(3-hydroxyoct-4-ynyl)-5-oxocyclopentyl]heptanoate Chemical compound CCCC#CC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCCC(F)C(=O)OCC GBGIDJVCWZHVAL-LHQJTOJGSA-N 0.000 description 1
- CEBKEJBROAURDZ-UHFFFAOYSA-N ethyl 4-(3-hydroxy-5-oxocyclopenten-1-yl)butanoate Chemical compound CCOC(=O)CCCC1=CC(O)CC1=O CEBKEJBROAURDZ-UHFFFAOYSA-N 0.000 description 1
- CQWSOQHCMBEHCV-UHFFFAOYSA-N ethyl 5-(3-bromo-5-oxocyclopenten-1-yl)pentanoate Chemical compound CCOC(=O)CCCCC1=CC(Br)CC1=O CQWSOQHCMBEHCV-UHFFFAOYSA-N 0.000 description 1
- WUUGWIGWYIHZGC-UHFFFAOYSA-N ethyl 5-(3-hydroxy-5-oxocyclopenten-1-yl)pentanoate Chemical compound CCOC(=O)CCCCC1=CC(O)CC1=O WUUGWIGWYIHZGC-UHFFFAOYSA-N 0.000 description 1
- GITZZMKJBSDDRW-UHFFFAOYSA-N ethyl 6-(3-bromo-5-oxocyclopenten-1-yl)hexanoate Chemical compound CCOC(=O)CCCCCC1=CC(Br)CC1=O GITZZMKJBSDDRW-UHFFFAOYSA-N 0.000 description 1
- RUBQKBQBOJRABF-UHFFFAOYSA-N ethyl 6-(3-hydroxy-5-oxocyclopenten-1-yl)hexanoate Chemical compound CCOC(=O)CCCCCC1=CC(O)CC1=O RUBQKBQBOJRABF-UHFFFAOYSA-N 0.000 description 1
- UKNHFUXRPYOQOJ-UHFFFAOYSA-N ethyl 6-(6-oxocyclohexen-1-yl)hexanoate Chemical compound CCOC(=O)CCCCCC1=CCCCC1=O UKNHFUXRPYOQOJ-UHFFFAOYSA-N 0.000 description 1
- FKMQGORIZFVJMB-UHFFFAOYSA-N ethyl 7-(3-bromo-5-oxocyclopenten-1-yl)-2-ethylheptanoate Chemical compound CCOC(=O)C(CC)CCCCCC1=CC(Br)CC1=O FKMQGORIZFVJMB-UHFFFAOYSA-N 0.000 description 1
- BCNUUDSCVOVDLB-UHFFFAOYSA-N ethyl 7-(3-bromo-5-oxocyclopenten-1-yl)-2-fluoroheptanoate Chemical compound CCOC(=O)C(F)CCCCCC1=CC(Br)CC1=O BCNUUDSCVOVDLB-UHFFFAOYSA-N 0.000 description 1
- SPOCVHPIRACBSX-UHFFFAOYSA-N ethyl 7-(3-bromo-5-oxocyclopenten-1-yl)-2-phenylheptanoate Chemical compound C=1C=CC=CC=1C(C(=O)OCC)CCCCCC1=CC(Br)CC1=O SPOCVHPIRACBSX-UHFFFAOYSA-N 0.000 description 1
- UVJIDHLDOBGQNK-UHFFFAOYSA-N ethyl 7-(3-bromo-5-oxocyclopenten-1-yl)heptanoate Chemical compound CCOC(=O)CCCCCCC1=CC(Br)CC1=O UVJIDHLDOBGQNK-UHFFFAOYSA-N 0.000 description 1
- CIFYRCPHHCLZCL-UHFFFAOYSA-N ethyl 7-(3-hydroxy-5-oxocyclopenten-1-yl)-2-phenylheptanoate Chemical compound C=1C=CC=CC=1C(C(=O)OCC)CCCCCC1=CC(O)CC1=O CIFYRCPHHCLZCL-UHFFFAOYSA-N 0.000 description 1
- GIHJKKVDUMHSEV-UHFFFAOYSA-N ethyl 7-(3-hydroxy-5-oxocyclopenten-1-yl)-3,3-dimethylheptanoate Chemical compound CCOC(=O)CC(C)(C)CCCCC1=CC(O)CC1=O GIHJKKVDUMHSEV-UHFFFAOYSA-N 0.000 description 1
- MSIXBIULXDPSOX-GMIDLEKQSA-N ethyl 7-[(1R,2S)-2-(3-hydroxyoct-4-ynyl)-5-oxocyclopentyl]-2-phenylheptanoate Chemical compound CCCC#CC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCCC(C(=O)OCC)C1=CC=CC=C1 MSIXBIULXDPSOX-GMIDLEKQSA-N 0.000 description 1
- ARSGVHMIQJEFAV-SJBAFXMYSA-N ethyl 7-[(1r,2s)-2-(3-hydroxyoct-4-ynyl)-5-oxocyclopentyl]heptanoate Chemical compound CCCC#CC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCCCC(=O)OCC ARSGVHMIQJEFAV-SJBAFXMYSA-N 0.000 description 1
- HYSILYBSJXIXAL-UHFFFAOYSA-N ethyl 8-(3-bromo-5-oxocyclopenten-1-yl)octanoate Chemical compound CCOC(=O)CCCCCCCC1=CC(Br)CC1=O HYSILYBSJXIXAL-UHFFFAOYSA-N 0.000 description 1
- VOIUAIRDAFSZRM-UHFFFAOYSA-N ethyl 8-(3-hydroxy-5-oxocyclopenten-1-yl)octanoate Chemical compound CCOC(=O)CCCCCCCC1=CC(O)CC1=O VOIUAIRDAFSZRM-UHFFFAOYSA-N 0.000 description 1
- JRHRVEKFQXSAMJ-UHFFFAOYSA-N ethyl 9-(3-bromo-5-oxocyclopenten-1-yl)nonanoate Chemical compound CCOC(=O)CCCCCCCCC1=CC(Br)CC1=O JRHRVEKFQXSAMJ-UHFFFAOYSA-N 0.000 description 1
- PFSMPGPGOZEVII-UHFFFAOYSA-N ethyl 9-(3-hydroxy-5-oxocyclopenten-1-yl)nonanoate Chemical compound CCOC(=O)CCCCCCCCC1=CC(O)CC1=O PFSMPGPGOZEVII-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- UAIZDWNSWGTKFZ-UHFFFAOYSA-L ethylaluminum(2+);dichloride Chemical compound CC[Al](Cl)Cl UAIZDWNSWGTKFZ-UHFFFAOYSA-L 0.000 description 1
- UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 1
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- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
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- 208000021822 hypotensive Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
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- 238000010253 intravenous injection Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
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- 125000000468 ketone group Chemical group 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
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- XESVFXQPJIFWRB-UHFFFAOYSA-N methyl 7-(3-bromo-5-oxocyclopenten-1-yl)heptanoate Chemical compound COC(=O)CCCCCCC1=CC(Br)CC1=O XESVFXQPJIFWRB-UHFFFAOYSA-N 0.000 description 1
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- RMSROFOPTSOXCN-UHFFFAOYSA-N methyl 7-[3-(oxan-2-yloxy)-5-oxocyclopenten-1-yl]heptanoate Chemical compound C1C(=O)C(CCCCCCC(=O)OC)=CC1OC1OCCCC1 RMSROFOPTSOXCN-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 235000010981 methylcellulose Nutrition 0.000 description 1
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- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VUGRNZHKYVHZSN-UHFFFAOYSA-N oct-1-yn-3-ol Chemical compound CCCCCC(O)C#C VUGRNZHKYVHZSN-UHFFFAOYSA-N 0.000 description 1
- IRUCBBFNLDIMIK-UHFFFAOYSA-N oct-4-ene Chemical compound CCCC=CCCC IRUCBBFNLDIMIK-UHFFFAOYSA-N 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
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- 235000021317 phosphate Nutrition 0.000 description 1
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- PPTCQVOXIJIQIE-UHFFFAOYSA-N propan-2-yl 7-(3-hydroxy-5-oxocyclopenten-1-yl)heptanoate Chemical compound CC(C)OC(=O)CCCCCCC1=CC(O)CC1=O PPTCQVOXIJIQIE-UHFFFAOYSA-N 0.000 description 1
- ZJCIMEZJSFQWQX-SIGULFFNSA-N propan-2-yl 7-[(1R,2S)-2-(3-hydroxyoct-4-ynyl)-5-oxocyclopentyl]heptanoate Chemical compound CCCC#CC(O)CC[C@H]1CCC(=O)[C@@H]1CCCCCCC(=O)OC(C)C ZJCIMEZJSFQWQX-SIGULFFNSA-N 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
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- 230000000171 quenching effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
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- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 238000005584 silyl ether cleavage reaction Methods 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
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- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 101150068774 thyX gene Proteins 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 238000005583 trifluoroacetylation reaction Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- ORYGRKHDLWYTKX-UHFFFAOYSA-N trihexylalumane Chemical compound CCCCCC[Al](CCCCCC)CCCCCC ORYGRKHDLWYTKX-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- CNWZYDSEVLFSMS-UHFFFAOYSA-N tripropylalumane Chemical compound CCC[Al](CCC)CCC CNWZYDSEVLFSMS-UHFFFAOYSA-N 0.000 description 1
- USJZIJNMRRNDPO-UHFFFAOYSA-N tris-decylalumane Chemical compound CCCCCCCCCC[Al](CCCCCCCCCC)CCCCCCCCCC USJZIJNMRRNDPO-UHFFFAOYSA-N 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 238000001132 ultrasonic dispersion Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/10—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of ethers, including cyclic ethers, e.g. oxiranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
- C07C29/42—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing triple carbon-to-carbon bonds, e.g. with metal-alkynes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0016—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing only hydroxy, etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0025—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing keto groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
- C07C405/0033—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing sulfur
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- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/04—Saturated ethers
- C07C43/12—Saturated ethers containing halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/06—Aluminium compounds
- C07F5/061—Aluminium compounds with C-aluminium linkage
- C07F5/062—Al linked exclusively to C
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5407—Acyclic saturated phosphonium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US27476872A | 1972-07-24 | 1972-07-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
DE2337343A1 true DE2337343A1 (de) | 1974-03-14 |
Family
ID=23049539
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19732337343 Ceased DE2337343A1 (de) | 1972-07-24 | 1973-07-23 | Porstancarbonsaeure- und prostencarbonsaeurederivate, zwischenprodukte und verfahren zur herstellung von biologisch wichtigen verbindungen der prostaglandinart |
Country Status (7)
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2415765A1 (de) * | 1973-03-30 | 1974-10-10 | Searle & Co | 3-hydroxy-5-oxo-2-substituierte cyclopentanalkensaeuren |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MXPA05007341A (es) * | 2003-01-10 | 2005-09-30 | Hoffmann La Roche | Derivados de 2-piperidona como agonistas de prostaglandina. |
-
1973
- 1973-07-18 GB GB3429073A patent/GB1444963A/en not_active Expired
- 1973-07-23 DE DE19732337343 patent/DE2337343A1/de not_active Ceased
- 1973-07-23 CA CA73177024A patent/CA1049022A/en not_active Expired
- 1973-07-24 FR FR7327073A patent/FR2193614B1/fr not_active Expired
- 1973-07-24 BE BE133805A patent/BE802718A/xx unknown
- 1973-07-24 NL NL7310277A patent/NL7310277A/xx not_active Application Discontinuation
- 1973-07-24 JP JP8351773A patent/JPS4985049A/ja active Pending
-
1981
- 1981-07-10 JP JP10805181A patent/JPS57131737A/ja active Pending
- 1981-07-10 JP JP10805081A patent/JPS5946946B2/ja not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2415765A1 (de) * | 1973-03-30 | 1974-10-10 | Searle & Co | 3-hydroxy-5-oxo-2-substituierte cyclopentanalkensaeuren |
Also Published As
Publication number | Publication date |
---|---|
JPS5946946B2 (ja) | 1984-11-15 |
AU5831073A (en) | 1975-01-23 |
BE802718A (fr) | 1974-01-24 |
JPS57114584A (en) | 1982-07-16 |
FR2193614A1 (US06653308-20031125-C00199.png) | 1974-02-22 |
FR2193614B1 (US06653308-20031125-C00199.png) | 1977-04-22 |
JPS4985049A (US06653308-20031125-C00199.png) | 1974-08-15 |
GB1444963A (en) | 1976-08-04 |
CA1049022A (en) | 1979-02-20 |
JPS57131737A (en) | 1982-08-14 |
NL7310277A (US06653308-20031125-C00199.png) | 1974-01-28 |
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