JP6563921B2 - 多価不飽和ケトン化合物の製造方法 - Google Patents
多価不飽和ケトン化合物の製造方法 Download PDFInfo
- Publication number
- JP6563921B2 JP6563921B2 JP2016528529A JP2016528529A JP6563921B2 JP 6563921 B2 JP6563921 B2 JP 6563921B2 JP 2016528529 A JP2016528529 A JP 2016528529A JP 2016528529 A JP2016528529 A JP 2016528529A JP 6563921 B2 JP6563921 B2 JP 6563921B2
- Authority
- JP
- Japan
- Prior art keywords
- polyunsaturated
- container
- thiol
- octadeca
- thioester
- 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 - Fee Related
Links
- 238000000034 method Methods 0.000 title claims description 82
- -1 ketone compound Chemical class 0.000 title claims description 33
- 239000003963 antioxidant agent Substances 0.000 claims description 62
- 230000003078 antioxidant effect Effects 0.000 claims description 51
- 150000007970 thio esters Chemical class 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 38
- 150000003573 thiols Chemical class 0.000 claims description 38
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 33
- 150000001298 alcohols Chemical class 0.000 claims description 32
- 238000002156 mixing Methods 0.000 claims description 32
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 32
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 31
- 150000002148 esters Chemical class 0.000 claims description 29
- 150000002576 ketones Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 23
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 19
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 18
- 238000003818 flash chromatography Methods 0.000 claims description 16
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 15
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical group CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 15
- 125000005604 azodicarboxylate group Chemical group 0.000 claims description 14
- 230000005595 deprotonation Effects 0.000 claims description 12
- 238000010537 deprotonation reaction Methods 0.000 claims description 12
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 12
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 claims description 12
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims description 10
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 239000011732 tocopherol Substances 0.000 claims description 10
- 229930003799 tocopherol Natural products 0.000 claims description 10
- 235000010384 tocopherol Nutrition 0.000 claims description 10
- 229960001295 tocopherol Drugs 0.000 claims description 10
- ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 claims description 8
- UMZOWPPFHRRPDC-IIFHDYRKSA-N (2E,6Z,9Z,12Z,15Z)-octadeca-2,6,9,12,15-pentaen-1-ol Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/CC\C=C\CO UMZOWPPFHRRPDC-IIFHDYRKSA-N 0.000 claims description 7
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000468 ketone group Chemical group 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- ORLHWMAIFDLKJV-IIFHDYRKSA-N (2e,6z,9z,12z,15z)-octadeca-2,6,9,12,15-pentaene-1-thiol Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/CC\C=C\CS ORLHWMAIFDLKJV-IIFHDYRKSA-N 0.000 claims description 3
- SRXRRKRCCNIEGC-JLNKQSITSA-N (3z,6z,9z,12z,15z)-octadeca-3,6,9,12,15-pentaen-1-ol Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCO SRXRRKRCCNIEGC-JLNKQSITSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- BGLVYMRQKGDTSV-JLNKQSITSA-N (3z,6z,9z,12z,15z)-octadeca-3,6,9,12,15-pentaene-1-thiol Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCS BGLVYMRQKGDTSV-JLNKQSITSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- YLODAJLHGUNNMN-MZESORTBSA-N s-[(2e,6z,9z,12z,15z)-octadeca-2,6,9,12,15-pentaenyl] ethanethioate Chemical group CC\C=C/C\C=C/C\C=C/C\C=C/CC\C=C\CSC(C)=O YLODAJLHGUNNMN-MZESORTBSA-N 0.000 claims description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims 3
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical class CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims 1
- 125000002640 tocopherol group Chemical group 0.000 claims 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 58
- 235000006708 antioxidants Nutrition 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 39
- 239000000047 product Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000012535 impurity Substances 0.000 description 15
- 238000006317 isomerization reaction Methods 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 238000007254 oxidation reaction Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 230000003647 oxidation Effects 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000006751 Mitsunobu reaction Methods 0.000 description 10
- 229940087168 alpha tocopherol Drugs 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000011521 glass Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 229960000984 tocofersolan Drugs 0.000 description 9
- 239000002076 α-tocopherol Substances 0.000 description 9
- 235000004835 α-tocopherol Nutrition 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical class CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 150000003003 phosphines Chemical class 0.000 description 5
- 239000008399 tap water Substances 0.000 description 5
- 235000020679 tap water Nutrition 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000007654 immersion Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 3
- 239000011609 ammonium molybdate Substances 0.000 description 3
- 235000018660 ammonium molybdate Nutrition 0.000 description 3
- 229940010552 ammonium molybdate Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical class FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 2
- LHTVMBMETNGEAN-PLNGDYQASA-N (z)-pent-1-en-1-ol Chemical compound CCC\C=C/O LHTVMBMETNGEAN-PLNGDYQASA-N 0.000 description 2
- RBPYIYOPSGHFQG-IIFHDYRKSA-N 1,1,1-trifluoro-3-[(2e,6z,9z,12z,15z)-octadeca-2,6,9,12,15-pentaenyl]sulfanylpropan-2-one Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/CC\C=C\CSCC(=O)C(F)(F)F RBPYIYOPSGHFQG-IIFHDYRKSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 2
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 101150105133 RRAD gene Proteins 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000007806 chemical reaction intermediate Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 description 2
- 229940043349 potassium metabisulfite Drugs 0.000 description 2
- 235000010263 potassium metabisulphite Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003384 small molecules Chemical group 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 2
- 229940035024 thioglycerol Drugs 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
- WHSJGOHDJIXULF-PLNGDYQASA-N (z)-pent-1-ene-1-thiol Chemical compound CCC\C=C/S WHSJGOHDJIXULF-PLNGDYQASA-N 0.000 description 1
- MBGFSSHDEMMNDM-JLNKQSITSA-N 1,1,1-trifluoro-3-[(3z,6z,9z,12z,15z)-octadeca-3,6,9,12,15-pentaenyl]sulfanylpropan-2-one Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCSCC(=O)C(F)(F)F MBGFSSHDEMMNDM-JLNKQSITSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- QULIOZDJZXKLNY-UHFFFAOYSA-N 3,4,5-trihydroxy-2-propylbenzoic acid Chemical compound CCCC1=C(O)C(O)=C(O)C=C1C(O)=O QULIOZDJZXKLNY-UHFFFAOYSA-N 0.000 description 1
- GOEGBJDTWXTPHP-UHFFFAOYSA-N 4-diphenylphosphanyl-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 GOEGBJDTWXTPHP-UHFFFAOYSA-N 0.000 description 1
- XYGKGASSKJWLTN-UHFFFAOYSA-N CCCCCCC.CCCCCCC Chemical compound CCCCCCC.CCCCCCC XYGKGASSKJWLTN-UHFFFAOYSA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- VPLLTGLLUHLIHA-UHFFFAOYSA-N dicyclohexyl(phenyl)phosphane Chemical compound C1CCCCC1P(C=1C=CC=CC=1)C1CCCCC1 VPLLTGLLUHLIHA-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LVTCZSBUROAWTE-UHFFFAOYSA-N diethyl(phenyl)phosphane Chemical compound CCP(CC)C1=CC=CC=C1 LVTCZSBUROAWTE-UHFFFAOYSA-N 0.000 description 1
- LLZAIAIZAVMQIG-UHFFFAOYSA-N diphenyl(propan-2-yl)phosphane Chemical compound C=1C=CC=CC=1P(C(C)C)C1=CC=CC=C1 LLZAIAIZAVMQIG-UHFFFAOYSA-N 0.000 description 1
- SVABQOITNJTVNJ-UHFFFAOYSA-N diphenyl-2-pyridylphosphine Chemical compound C1=CC=CC=C1P(C=1N=CC=CC=1)C1=CC=CC=C1 SVABQOITNJTVNJ-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- 229940090949 docosahexaenoic acid Drugs 0.000 description 1
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 1
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 1
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- CHXARDKIHSVFDK-UHFFFAOYSA-N hexylphosphane Chemical compound CCCCCCP CHXARDKIHSVFDK-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- NRPKURNSADTHLJ-UHFFFAOYSA-N octyl gallate Chemical compound CCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 NRPKURNSADTHLJ-UHFFFAOYSA-N 0.000 description 1
- 235000010387 octyl gallate Nutrition 0.000 description 1
- 239000000574 octyl gallate Substances 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- WHSJGOHDJIXULF-UHFFFAOYSA-N pent-1-ene-1-thiol Chemical compound CCCC=CS WHSJGOHDJIXULF-UHFFFAOYSA-N 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- UPDNYUVJHQABBS-UHFFFAOYSA-N phenoxy(diphenyl)phosphane Chemical compound C=1C=CC=CC=1OP(C=1C=CC=CC=1)C1=CC=CC=C1 UPDNYUVJHQABBS-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- RMZAYIKUYWXQPB-UHFFFAOYSA-N trioctylphosphane Chemical compound CCCCCCCCP(CCCCCCCC)CCCCCCCC RMZAYIKUYWXQPB-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/26—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1313238.6A GB201313238D0 (en) | 2013-07-24 | 2013-07-24 | Process for the preparation of a polyunsaturated ketone compound |
| GB1313238.6 | 2013-07-24 | ||
| PCT/EP2014/065853 WO2015011206A1 (en) | 2013-07-24 | 2014-07-23 | Process for the preparation of a polyunsaturated ketone compound |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017501118A JP2017501118A (ja) | 2017-01-12 |
| JP2017501118A5 JP2017501118A5 (enExample) | 2018-03-15 |
| JP6563921B2 true JP6563921B2 (ja) | 2019-08-21 |
Family
ID=49119228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016528529A Expired - Fee Related JP6563921B2 (ja) | 2013-07-24 | 2014-07-23 | 多価不飽和ケトン化合物の製造方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10093618B2 (enExample) |
| EP (2) | EP3398936A1 (enExample) |
| JP (1) | JP6563921B2 (enExample) |
| KR (1) | KR20160033781A (enExample) |
| CN (2) | CN108276317A (enExample) |
| CA (1) | CA2918950A1 (enExample) |
| ES (1) | ES2668322T3 (enExample) |
| GB (1) | GB201313238D0 (enExample) |
| HK (1) | HK1258174A1 (enExample) |
| IL (1) | IL243636B (enExample) |
| NO (1) | NO3024818T3 (enExample) |
| WO (1) | WO2015011206A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201501144D0 (en) | 2015-01-23 | 2015-03-11 | Avexxin As | Process for the preparation of a polyunsaturated ketone compound |
| CN106117096B (zh) * | 2016-06-15 | 2018-01-19 | 苏州大学 | 一种非对称硫醚的合成方法 |
| CN106831511B (zh) * | 2017-01-24 | 2018-05-25 | 郯城博化化工科技有限公司 | 一种多元硫醇化合物的制备方法 |
| GB201807892D0 (en) | 2018-05-15 | 2018-06-27 | Avexxin As | Processes in the preparation of polyunsaturated ketone compounds |
| WO2025192727A1 (ja) * | 2024-03-15 | 2025-09-18 | 国立大学法人福井大学 | 硫黄含有ビニルエーテルの製造方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5024847A (en) * | 1989-09-18 | 1991-06-18 | Basf K&F Corporation | Sulfur containing acyclic terpenes |
| JPH0632773A (ja) | 1992-07-15 | 1994-02-08 | Sumitomo Seika Chem Co Ltd | ４，４’−チオビスベンゼンチオールの製造法 |
| CA2260859A1 (en) * | 1996-07-22 | 1998-01-29 | Monsanto Company | Thiol sulfone metalloprotease inhibitors |
| WO2002100991A2 (en) | 2001-06-13 | 2002-12-19 | Biorama 2000 S.R.L. | Mono-, di- and triglycerides or their mixtures containing trans-fatty acid residues and method of their formation |
| GB0202002D0 (en) | 2002-01-29 | 2002-03-13 | Leiv Eiriksson Nyotek A S | Use |
| CN101899063B (zh) * | 2002-12-11 | 2012-12-12 | 布里斯托尔-迈尔斯斯奎布公司 | 制备抗病毒药[1S-(1α,3α,4β)]-2-氨基-1,9-二氢-9-[4-羟基-3-(羟甲基)-2-亚甲环戊基]-6H-嘌呤-6-酮的方法 |
| EP2147910A1 (en) | 2008-07-15 | 2010-01-27 | Pronova BioPharma Norge AS | Novel lipid compounds |
| JP5349086B2 (ja) | 2009-03-05 | 2013-11-20 | 長谷川香料株式会社 | α，α−ジチオール化合物および香料組成物 |
| GB0909643D0 (en) | 2009-06-04 | 2009-07-22 | Avexxin As | Glomerulonephritis treatment |
| GB201014633D0 (en) | 2010-09-02 | 2010-10-13 | Avexxin As | Rheumatoid arthritis treatment |
| GB201221329D0 (en) | 2012-11-27 | 2013-01-09 | Avexxin As | Dermatitis treatment |
-
2013
- 2013-07-24 GB GBGB1313238.6A patent/GB201313238D0/en not_active Ceased
-
2014
- 2014-07-23 JP JP2016528529A patent/JP6563921B2/ja not_active Expired - Fee Related
- 2014-07-23 ES ES14742219.0T patent/ES2668322T3/es active Active
- 2014-07-23 CN CN201810252228.8A patent/CN108276317A/zh active Pending
- 2014-07-23 CN CN201480044978.6A patent/CN105492421B/zh not_active Expired - Fee Related
- 2014-07-23 US US14/907,147 patent/US10093618B2/en not_active Expired - Fee Related
- 2014-07-23 EP EP18164396.6A patent/EP3398936A1/en not_active Withdrawn
- 2014-07-23 WO PCT/EP2014/065853 patent/WO2015011206A1/en not_active Ceased
- 2014-07-23 EP EP14742219.0A patent/EP3024818B1/en not_active Not-in-force
- 2014-07-23 CA CA2918950A patent/CA2918950A1/en not_active Abandoned
- 2014-07-23 KR KR1020167004651A patent/KR20160033781A/ko not_active Ceased
- 2014-07-23 NO NO14742219A patent/NO3024818T3/no unknown
-
2016
- 2016-01-17 IL IL243636A patent/IL243636B/en active IP Right Grant
-
2019
- 2019-01-14 HK HK19100531.5A patent/HK1258174A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO3024818T3 (enExample) | 2018-09-01 |
| IL243636B (en) | 2019-02-28 |
| ES2668322T3 (es) | 2018-05-17 |
| WO2015011206A1 (en) | 2015-01-29 |
| US10093618B2 (en) | 2018-10-09 |
| EP3024818B1 (en) | 2018-04-04 |
| GB201313238D0 (en) | 2013-09-04 |
| HK1258174A1 (zh) | 2019-11-08 |
| KR20160033781A (ko) | 2016-03-28 |
| CN105492421B (zh) | 2018-04-20 |
| CA2918950A1 (en) | 2015-01-29 |
| HK1223910A1 (en) | 2017-08-11 |
| CN108276317A (zh) | 2018-07-13 |
| CN105492421A (zh) | 2016-04-13 |
| JP2017501118A (ja) | 2017-01-12 |
| EP3398936A1 (en) | 2018-11-07 |
| US20160159737A1 (en) | 2016-06-09 |
| EP3024818A1 (en) | 2016-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HK1258174A1 (zh) | 用於制备多元不饱和酮化合物的方法 | |
| EP1404643A4 (en) | CLEAVABLE SURFACES AND METHOD FOR THEIR USE | |
| RU2012138262A (ru) | Способы и устройство для синтезирования радиофармацевтических препаратов и их промежуточных продуктов | |
| CN107406375B (zh) | 制备不饱和酮化合物的方法 | |
| JP4818500B2 (ja) | トコトリエノール誘導体及びその製造方法 | |
| CN1680364A (zh) | 硫辛酸和二氢硫辛酸的制备方法 | |
| FR2573070A1 (fr) | Procede de preparation de composes carbonyles | |
| MXPA06006709A (es) | Proceso para sintetizar disulfuros. | |
| ES2670776T3 (es) | Métodos de fabricación de derivados de ácido 15-hidroxi graso | |
| HK1223910B (en) | Process for the preparation of a polyunsaturated ketone compound | |
| JPH07500325A (ja) | 環状パーオキシアセタール化合物 | |
| CA2098185A1 (fr) | Procede de preparation de derives de l'acide dihydroxy-3,5 pentanoique | |
| Duan et al. | Discovery of novel fluorine-containing parthenolide analogues as potential antitumor agents | |
| CN102093272B (zh) | 消旋卡多曲化合物及其制法 | |
| CN117534657B (zh) | 雷贝拉唑类似物的合成方法及应用 | |
| JPH07238079A (ja) | カテキン化合物、その製造方法およびこれを用いる消臭剤 | |
| WO2025257737A1 (en) | Process for the preparation of urolithin a and analogues thereof | |
| JP2016044161A (ja) | アトラクチロジン類の製造方法、及び、コバルト錯体化合物 | |
| JPH05320127A (ja) | 活性型ビタミンｄ誘導体 | |
| 釘田博至 et al. | Synthesis of 1, 5-Benzothiazepine Derivatives. II | |
| JPH04145036A (ja) | 新規フェノール誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170704 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180130 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180709 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180717 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20181011 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20181213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190111 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190115 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190509 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190524 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190627 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190725 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6563921 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |