JP2014521598A - ビタミンAの新規な中間体およびβ−カロテンの合成 - Google Patents
ビタミンAの新規な中間体およびβ−カロテンの合成 Download PDFInfo
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- JP2014521598A JP2014521598A JP2014516278A JP2014516278A JP2014521598A JP 2014521598 A JP2014521598 A JP 2014521598A JP 2014516278 A JP2014516278 A JP 2014516278A JP 2014516278 A JP2014516278 A JP 2014516278A JP 2014521598 A JP2014521598 A JP 2014521598A
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- palladium
- methyl
- copper
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- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 18
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 title claims abstract description 17
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 title claims abstract description 17
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 title claims abstract description 17
- 235000019155 vitamin A Nutrition 0.000 title claims abstract description 17
- 239000011719 vitamin A Substances 0.000 title claims abstract description 17
- 229940045997 vitamin a Drugs 0.000 title claims abstract description 17
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 12
- 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 title claims description 8
- 235000013734 beta-carotene Nutrition 0.000 title claims description 8
- 239000011648 beta-carotene Substances 0.000 title claims description 8
- 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 title claims description 8
- 229960002747 betacarotene Drugs 0.000 title claims description 8
- 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 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 23
- 239000003054 catalyst Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 14
- 229910052763 palladium Inorganic materials 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 8
- 239000010949 copper Substances 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 claims description 5
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical group [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 4
- ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 claims description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical group [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 3
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 claims description 3
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-butyl ethyl ether Chemical compound CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 claims description 3
- 239000003880 polar aprotic solvent Substances 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical group [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims 1
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- FDSDTBUPSURDBL-LOFNIBRQSA-N canthaxanthin Chemical compound CC=1C(=O)CCC(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)C(=O)CCC1(C)C FDSDTBUPSURDBL-LOFNIBRQSA-N 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(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)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 abstract description 2
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 abstract description 2
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 abstract description 2
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 abstract description 2
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 abstract description 2
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 abstract description 2
- 235000013793 astaxanthin Nutrition 0.000 abstract description 2
- 239000001168 astaxanthin Substances 0.000 abstract description 2
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(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)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 abstract description 2
- 229940022405 astaxanthin Drugs 0.000 abstract description 2
- 235000012682 canthaxanthin Nutrition 0.000 abstract description 2
- 239000001659 canthaxanthin Substances 0.000 abstract description 2
- 229940008033 canthaxanthin Drugs 0.000 abstract description 2
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 abstract description 2
- 235000010930 zeaxanthin Nutrition 0.000 abstract description 2
- 239000001775 zeaxanthin Substances 0.000 abstract description 2
- 229940043269 zeaxanthin Drugs 0.000 abstract description 2
- 150000001746 carotenes Chemical class 0.000 abstract 1
- 235000005473 carotenes Nutrition 0.000 abstract 1
- 235000021466 carotenoid Nutrition 0.000 abstract 1
- 150000001747 carotenoids Chemical class 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 239000012320 chlorinating reagent Substances 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ACLRHGVHKRXKRW-UHFFFAOYSA-N (4-chloro-3-methyl-4-oxobut-2-enyl) acetate Chemical compound CC(=O)OCC=C(C)C(Cl)=O ACLRHGVHKRXKRW-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 0 CC1(*)C(CC=C(C)C#C)=C(C)CCC1 Chemical compound CC1(*)C(CC=C(C)C#C)=C(C)CCC1 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- HWTAHDYIVQEYSX-UHFFFAOYSA-N [3,7-dimethyl-4-oxo-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,7-dien-5-ynyl] acetate Chemical compound CC(=O)OCC=C(C)C(=O)C#CC(C)=CCC1=C(C)CCCC1(C)C HWTAHDYIVQEYSX-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VMKAFJQFKBASMU-KRWDZBQOSA-N (3as)-1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C([C@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-KRWDZBQOSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WUGFRQORLBASOM-UHFFFAOYSA-N 1,3,3-trimethyl-2-(3-methylpent-2-en-4-ynyl)cyclohexene Chemical compound C#CC(C)=CCC1=C(C)CCCC1(C)C WUGFRQORLBASOM-UHFFFAOYSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- TWNDIMMESLJLQY-UHFFFAOYSA-N 4-acetyloxy-2-methylbut-2-enoic acid Chemical compound CC(=O)OCC=C(C)C(O)=O TWNDIMMESLJLQY-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 101150003085 Pdcl gene Proteins 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
- VMPVEPPRYRXYNP-UHFFFAOYSA-I antimony(5+);pentachloride Chemical compound Cl[Sb](Cl)(Cl)(Cl)Cl VMPVEPPRYRXYNP-UHFFFAOYSA-I 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- -1 copper (I) halide Chemical class 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PUPAWTXNPAJCHR-UHFFFAOYSA-N oxazaborole Chemical compound O1C=CB=N1 PUPAWTXNPAJCHR-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
- C07C403/12—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
- C07C403/08—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/14—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms
- C07C403/16—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by doubly-bound oxygen atoms not being part of —CHO groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
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- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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Abstract
Description
(式中、R1は、C1〜C15アルキル部位またはC2〜C18アルケニル部位を示す)に関する。R1がC1〜C15アルキル部位である場合には、次いで好ましくは、アルキル部位は直鎖状である。特に好ましいアルキル部位は、メチル、エチルおよびペンタデシルである。R1がC2〜C18アルケニル部位である場合には、式(I)の化合物は、3個を超えるC−C二重結合を有し得る。好ましくは、アルケニル部位は枝分かれしていない。
(式中、R1が、C1〜C15アルキル部位またはC2〜C18アルケニル部位を示す)
に関する。R1がC1〜C15アルキル部位である場合、次いで好ましくは、アルキル部位は直鎖状である。特に好ましいアルキル部位は、メチル、エチルおよびペンタデシルである。R1がC2−C18アルケニル部位である場合、式(II)の化合物は3個を超えるC−C二重結合を有し得る。好ましくは、アルケニル部位は枝分かれしていない。
(式中、R1は、C1〜C15アルキル部位またはC2〜C18アルケニル部位を示す)
を塩素化することによって製造することができる。R1がC1〜C15アルキル部位である場合に、次いで好ましくは、アルキル部位は直鎖状である。特に好ましいアルキル部位はメチル、エチルおよびペンタデシルである。R1がC2〜C18アルケニル部位である場合、式(V)の化合物は3個を超えるC−C二重結合を有し得る。好ましくは、アルケニル部位は枝分かれしていない。
[実施例1:3,7−ジメチル−4−オキソ−9−(2,6,6−トリメチルシクロヘキス−1−エニル)ノナ−2,7−ジエン−5−イニルアセテート(IIa)の4−ヒドロキシ−3,7−ジメチル−9−(2,6,6−トリメチルシクロへキス−1−エニル)ノナ−2,7−ジエン−5−イニルアセテート(Ia)への還元:]
500ml四つ口フラスコ中で、式(IIa)のケトン1.95g(5mmol)
を無水THF300mlに溶解した。黄色い溶液を氷浴で0℃に冷却した。シリンジを使用して、連続的に(S)−2−メチル−CBS−オキサザボロリジン(トルエン中1M)10ml(10mmol)およびボランジメチルスルフィド錯体1.2ml(11.25mmol)を一滴ずつ添加した。40分後、無色の溶液を24℃に温めた。次いで、メタノール150mlを添加し、ガスの形成が止まるまで攪拌を続けた。減圧下にて(350〜20ミリバール)、溶媒を40℃で除去した。収率92%で黄色いオイルとして粗生成物が得られた。次いで、生成物(式(Ia)の化合物)を精製した。精製された生成物の収率は87%であった。
2−メチル−4−アセチルオキシ−2−ブテン酸(式(Va)の化合物)
3.2g(19.73mmol)を、トルエン11.4mlおよびN,N−ジメチルホルムアミド(DMF)300μlと混合した。反応混合物の温度を水浴で20℃に維持しながら、塩化オキサリル2.78g(21.70mmol)を反応混合物にゆっくりと添加した。室温で攪拌して2.5時間後、50℃および30ミリバールで溶媒を除去した。赤茶色のオイル(3.83g)が得られ、それを精製した。わずかに黄色の液体が得られた。4−クロロ−3−メチル−4−オキソブト−2−エニルアセテート(式(IVa)の化合物)の収率は99%であった。
不活性ガス雰囲気下にて、塩化銅(I)59.9mg(0.308mmol)およびビス(トリフェニルホスフィン)パラジウム(II)ジクロリド[(PPh3)2PdCl2]110.3mg(0.154mmol)を100ml四つ口フラスコに添加した。23℃にて、無水THF42.0mlを添加し、黄色い懸濁液を5分間攪拌した。シリンジを使用して、トリエチルアミン2.15ml(15.4mmol)を一滴ずつ添加すると、オレンジ色の溶液が得られた。1分以内に4−クロロ−3−メチル−4−オキソブト−2−エニルアセテート(式(IVa)の化合物)3.10g(15.4mmol)を添加し、溶液が暗いオレンジ色に変わった。1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エン(式(III)の化合物)
2.92g(14.0mmol)を5分間にわたって一滴ずつ添加し、黄色い懸濁液が形成された。反応混合物を室温に冷却し、GCおよびTLCによってモニターした。23℃で2時間20分後、すべての出発原料が消費された。反応混合物を分液漏斗に移し、ジエチルエーテル80mlで希釈し、半濃縮重炭酸ナトリウム溶液(80ml)で洗浄した。層を分離し、水層をジエチルエーテル(2×75ml)で抽出した。合わせた有機層を半飽和重炭酸ナトリウム溶液80mlで洗浄し、硫酸ナトリウムで乾燥させ、乾燥状態まで濃縮した。粗生成物(式(IIa)の化合物)
が茶色のオイル(5.44g,純度82%,収率93%)として得られ、カラムクロマトグラフィーおよび木炭処理によって精製された。
Claims (23)
- R1が直鎖状C1〜C15アルキル部位である、請求項1に記載の化合物。
- R1がメチル、エチルまたはペンタデシルである、請求項1および2に記載の化合物。
- R1が、3個を超えるC−C二重結合を有する非分岐C2〜C18アルケニル部位である、請求項1に記載の化合物。
- 式(I)の化合物が純粋な立体異性体形である、請求項1から4のいずれか一項に記載の化合物。
- 式(I)の化合物が立体異性体形の混合物である、請求項1から4のいずれか一項に記載の化合物。
- R1が直鎖状C1〜C15アルキル部位である、請求項8に記載の化合物。
- R1がメチル、エチルまたはペンタデシルである、請求項8および9に記載の化合物。
- R1が、3個を超えるC−C二重結合を有する非分岐C2〜C18アルケニル部位である、請求項8に記載の化合物。
- 式(I)の化合物が純粋な立体異性体形である、請求項8から11のいずれか一項に記載の化合物。
- 式(I)の化合物が立体異性体形の混合物である、請求項8から11のいずれか一項に記載の化合物。
- 極性非プロトン性溶媒(または非プロトン性溶媒の混合物)、好ましくはTHF、メチル−THF、メチルシクロペンチルエーテル、t−ブチルメチルエーテル、t−ブチルエチルエーテル、t−アミルメチルエーテルまたはその混合物中で行われる、請求項14に記載のプロセス。
- 基質とパラジウム触媒とのモル比が、2000:1〜10:1、好ましくは1000:1〜50:1の範囲である、請求項14または15に記載のプロセス。
- 銅触媒とパラジウム触媒とのモル比が、1.1:1〜10:1、好ましくは1.5:1〜5:1、特に好ましくは1.8:1〜3:1の範囲である、請求項14から16のいずれか一項に記載のプロセス。
- 前記パラジウム触媒が、ビス(トリアリールホスフィン)パラジウム(II)ジハライドであり、かつ前記銅触媒が銅(I)塩である、請求項14から17のいずれか一項に記載のプロセス。
- 前記パラジウム触媒が、キレート化ビス(ジアリールホスフィノアルカン)パラジウム(II)ジハライドであり、かつ前記銅触媒が銅(I)塩である、請求項14から17のいずれか一項に記載のプロセス。
- アルカンが直鎖状C2〜C6アルキル部位である、請求項19に記載のキレート化ビス(ジアリールホスフィノアルカン)パラジウム(II)ジハライド。
- 前記パラジウム触媒が、ビス(トリフェニルホスフィン)パラジウム(II)ジクロリドであり、かつ前記銅触媒が塩化銅(I)である、請求項10から13のいずれか一項に記載のプロセス。
- 有機合成における、好ましくはビタミンAまたはβ−カロテンまたはその誘導体の合成における中間体(構成単位)としての、請求項1から6のいずれか一項に記載の化合物の使用。
- 有機合成における、好ましくはビタミンAまたはβ−カロテンまたはその誘導体の合成における中間体(構成単位)としての、請求項8から13のいずれか一項に記載の化合物の使用。
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JP2021535101A (ja) * | 2018-08-20 | 2021-12-16 | アディッソ・フランス・エス.エー.エス.Adisseo France S.A.S. | ビタミンaの合成方法 |
JP2022528611A (ja) * | 2019-04-15 | 2022-06-15 | ディーエスエム アイピー アセッツ ビー.ブイ. | 新規なエノールアセテート |
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JP2014522812A (ja) * | 2011-06-22 | 2014-09-08 | ディーエスエム アイピー アセッツ ビー.ブイ. | 1,3,3−トリメチル−2−(3−メチルペント−2−エン−4−イニル)シクロヘキス−1−エンを製造する方法 |
JP2021535101A (ja) * | 2018-08-20 | 2021-12-16 | アディッソ・フランス・エス.エー.エス.Adisseo France S.A.S. | ビタミンaの合成方法 |
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