JP5924479B2 - β−ジヒドロフラン誘導化合物、β−ジヒドロフラン誘導化合物またはβ−テトラヒドロフラン誘導化合物の製造方法、並びにβ−グリコシド化合物の製造方法 - Google Patents
β−ジヒドロフラン誘導化合物、β−ジヒドロフラン誘導化合物またはβ−テトラヒドロフラン誘導化合物の製造方法、並びにβ−グリコシド化合物の製造方法 Download PDFInfo
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- JP5924479B2 JP5924479B2 JP2011553828A JP2011553828A JP5924479B2 JP 5924479 B2 JP5924479 B2 JP 5924479B2 JP 2011553828 A JP2011553828 A JP 2011553828A JP 2011553828 A JP2011553828 A JP 2011553828A JP 5924479 B2 JP5924479 B2 JP 5924479B2
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- butoxycarbonyl
- methyl
- group
- propoxycarbonyl
- pentyloxycarbonyl
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- 238000004519 manufacturing process Methods 0.000 title claims description 30
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- 125000006239 protecting group Chemical group 0.000 claims description 21
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 15
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 229910052707 ruthenium Inorganic materials 0.000 description 10
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- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 8
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- YSMHTFWPDRJCMN-UHFFFAOYSA-N butan-2-yl carbonochloridate Chemical compound CCC(C)OC(Cl)=O YSMHTFWPDRJCMN-UHFFFAOYSA-N 0.000 description 1
- YAGCIXJCAUGCGI-UHFFFAOYSA-N butoxycarbonyl butyl carbonate Chemical compound CCCCOC(=O)OC(=O)OCCCC YAGCIXJCAUGCGI-UHFFFAOYSA-N 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- YMBYDCYFUDVJSS-UHFFFAOYSA-N carbon monoxide;cyclopentane;iron Chemical class [Fe].[O+]#[C-].[O+]#[C-].[CH]1[CH][CH][CH][CH]1 YMBYDCYFUDVJSS-UHFFFAOYSA-N 0.000 description 1
- VPEFMEDXFAOQRR-UHFFFAOYSA-N carbon monoxide;cyclopentane;iron;sodium Chemical compound [Na].[Fe].[O+]#[C-].[O+]#[C-].[CH]1[CH][CH][CH][CH]1 VPEFMEDXFAOQRR-UHFFFAOYSA-N 0.000 description 1
- SZQABOJVTZVBHE-UHFFFAOYSA-N carbon monoxide;rhodium Chemical compound [Rh].[Rh].[Rh].[Rh].[Rh].[Rh].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] SZQABOJVTZVBHE-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
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- WOCPRDDAFVUUSI-UHFFFAOYSA-N chloroform;1,5-diphenylpenta-1,4-dien-3-one Chemical compound ClC(Cl)Cl.C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1.C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1.C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WOCPRDDAFVUUSI-UHFFFAOYSA-N 0.000 description 1
- ACRRLAATBVAFBT-UHFFFAOYSA-L chloropalladium(1+);2-methanidylprop-1-ene Chemical compound [Pd+]Cl.[Pd+]Cl.CC([CH2-])=C.CC([CH2-])=C ACRRLAATBVAFBT-UHFFFAOYSA-L 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- VZXMCMGRKFXJJA-UHFFFAOYSA-N cycloocta-1,3-diene cycloocta-1,3,5-triene ruthenium Chemical compound [Ru].C1CCC=CC=CC1.C1CC=CC=CC=C1 VZXMCMGRKFXJJA-UHFFFAOYSA-N 0.000 description 1
- GZOYVTSTDWWHPD-UHFFFAOYSA-N cycloocta-1,5-diene;platinum Chemical compound [Pt].C1CC=CCCC=C1.C1CC=CCCC=C1 GZOYVTSTDWWHPD-UHFFFAOYSA-N 0.000 description 1
- SPKJCVZOZISLEI-UHFFFAOYSA-N cyclopenta-1,3-diene;1-cyclopenta-1,3-dien-1-ylethanone;iron(2+) Chemical compound [Fe+2].C=1C=C[CH-]C=1.CC(=O)C1=CC=C[CH-]1 SPKJCVZOZISLEI-UHFFFAOYSA-N 0.000 description 1
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
- FJHVNFBZMNBXJC-UHFFFAOYSA-N decoxycarbonyl decyl carbonate Chemical compound CCCCCCCCCCOC(=O)OC(=O)OCCCCCCCCCC FJHVNFBZMNBXJC-UHFFFAOYSA-N 0.000 description 1
- AZZCHVHSWUYCQA-UHFFFAOYSA-N decyl carbonochloridate Chemical compound CCCCCCCCCCOC(Cl)=O AZZCHVHSWUYCQA-UHFFFAOYSA-N 0.000 description 1
- 238000006389 diacetylation reaction Methods 0.000 description 1
- WIWBLJMBLGWSIN-UHFFFAOYSA-L dichlorotris(triphenylphosphine)ruthenium(ii) Chemical compound [Cl-].[Cl-].[Ru+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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 WIWBLJMBLGWSIN-UHFFFAOYSA-L 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 229940028356 diethylene glycol monobutyl ether Drugs 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000004316 dimethyl dicarbonate Substances 0.000 description 1
- 235000010300 dimethyl dicarbonate Nutrition 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- LDCRTTXIJACKKU-ARJAWSKDSA-N dimethyl maleate Chemical compound COC(=O)\C=C/C(=O)OC LDCRTTXIJACKKU-ARJAWSKDSA-N 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- CAEMOCUMMOVWCN-UHFFFAOYSA-N diphosphono hydrogen phosphate phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(=O)OP(O)(=O)OP(O)(O)=O CAEMOCUMMOVWCN-UHFFFAOYSA-N 0.000 description 1
- BNYJLDOKEIBKLV-UHFFFAOYSA-L disodium;3-[3-phosphanyl-2-(3-sulfonatophenyl)phenyl]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC=CC(C=2C(=C(P)C=CC=2)C=2C=C(C=CC=2)S([O-])(=O)=O)=C1 BNYJLDOKEIBKLV-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
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- 239000000890 drug combination Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
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- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
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- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
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- 239000007789 gas Substances 0.000 description 1
- SATRZZYUXUGZIE-UHFFFAOYSA-N heptyl carbonochloridate Chemical compound CCCCCCCOC(Cl)=O SATRZZYUXUGZIE-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZLKKDYSCTUTSNA-UHFFFAOYSA-N hexan-2-yl carbonochloridate Chemical compound CCCCC(C)OC(Cl)=O ZLKKDYSCTUTSNA-UHFFFAOYSA-N 0.000 description 1
- MTHDOZJQBLCTIN-UHFFFAOYSA-N hexan-2-yl hexan-2-yloxycarbonyl carbonate Chemical compound CCCCC(C)OC(=O)OC(=O)OC(C)CCCC MTHDOZJQBLCTIN-UHFFFAOYSA-N 0.000 description 1
- ZMSXSTNHWZHSLE-UHFFFAOYSA-N hexan-3-yl carbonochloridate Chemical compound CCCC(CC)OC(Cl)=O ZMSXSTNHWZHSLE-UHFFFAOYSA-N 0.000 description 1
- SZOZZORQMSMTJG-UHFFFAOYSA-N hexan-3-yl hexan-3-yloxycarbonyl carbonate Chemical compound CCCC(CC)OC(=O)OC(=O)OC(CC)CCC SZOZZORQMSMTJG-UHFFFAOYSA-N 0.000 description 1
- NSJDJKLTACXIPI-UHFFFAOYSA-N hexoxycarbonyl hexyl carbonate Chemical compound CCCCCCOC(=O)OC(=O)OCCCCCC NSJDJKLTACXIPI-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
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- SDTGEKAAGAIGJL-UHFFFAOYSA-N iron;1,2,3,4-tetramethylcyclopentane Chemical compound [Fe].C[C]1[CH][C](C)[C](C)[C]1C.C[C]1[CH][C](C)[C](C)[C]1C SDTGEKAAGAIGJL-UHFFFAOYSA-N 0.000 description 1
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- 239000010410 layer Substances 0.000 description 1
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- 238000004811 liquid chromatography Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
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- 231100000296 mitochondrial toxicity Toxicity 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- QHGBDBLWAYISBS-UHFFFAOYSA-N molybdenum;2-pyridin-2-ylpyridine Chemical compound [Mo].N1=CC=CC=C1C1=CC=CC=N1 QHGBDBLWAYISBS-UHFFFAOYSA-N 0.000 description 1
- QVMFDLLOVZUZLH-UHFFFAOYSA-N n,n-di(butan-2-yl)carbamoyl chloride Chemical compound CCC(C)N(C(Cl)=O)C(C)CC QVMFDLLOVZUZLH-UHFFFAOYSA-N 0.000 description 1
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- OYZTUIIWSUUXBE-UHFFFAOYSA-N n,n-dipentylcarbamoyl chloride Chemical compound CCCCCN(C(Cl)=O)CCCCC OYZTUIIWSUUXBE-UHFFFAOYSA-N 0.000 description 1
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
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- STKAALWGFPHJHN-UHFFFAOYSA-N octoxycarbonyl octyl carbonate Chemical compound CCCCCCCCOC(=O)OC(=O)OCCCCCCCC STKAALWGFPHJHN-UHFFFAOYSA-N 0.000 description 1
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- LCODWXJBYGHVLO-UHFFFAOYSA-N pentoxycarbonyl pentyl carbonate Chemical compound CCCCCOC(=O)OC(=O)OCCCCC LCODWXJBYGHVLO-UHFFFAOYSA-N 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- XAFJSPPHVXDRIE-UHFFFAOYSA-L platinum(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Pt+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 XAFJSPPHVXDRIE-UHFFFAOYSA-L 0.000 description 1
- USDYNYGJOWWFKL-UHFFFAOYSA-N platinum;triphenylphosphane Chemical compound [Pt].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 USDYNYGJOWWFKL-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 229910003450 rhodium oxide Inorganic materials 0.000 description 1
- SONJTKJMTWTJCT-UHFFFAOYSA-K rhodium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Rh+3] SONJTKJMTWTJCT-UHFFFAOYSA-K 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 1
- FZHCFNGSGGGXEH-UHFFFAOYSA-N ruthenocene Chemical compound [Ru+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 FZHCFNGSGGGXEH-UHFFFAOYSA-N 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NTUROZDXWLPVHB-UHFFFAOYSA-M sodium;3-diphenylphosphanylbenzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NTUROZDXWLPVHB-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- BRKFQVAOMSWFDU-UHFFFAOYSA-M tetraphenylphosphanium;bromide Chemical compound [Br-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BRKFQVAOMSWFDU-UHFFFAOYSA-M 0.000 description 1
- AEFPPQGZJFTXDR-UHFFFAOYSA-M tetraphenylphosphanium;iodide Chemical compound [I-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 AEFPPQGZJFTXDR-UHFFFAOYSA-M 0.000 description 1
- WAGFXJQAIZNSEQ-UHFFFAOYSA-M tetraphenylphosphonium chloride Chemical compound [Cl-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WAGFXJQAIZNSEQ-UHFFFAOYSA-M 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940036565 thiouracil antithyroid preparations Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 125000005607 tigloyl group Chemical group 0.000 description 1
- 125000005389 trialkylsiloxy group Chemical group 0.000 description 1
- XTTGYFREQJCEML-UHFFFAOYSA-N tributyl phosphite Chemical group CCCCOP(OCCCC)OCCCC XTTGYFREQJCEML-UHFFFAOYSA-N 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- FWYKRJUVEOBFGH-UHFFFAOYSA-M triphenyl(prop-2-enyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC=C)C1=CC=CC=C1 FWYKRJUVEOBFGH-UHFFFAOYSA-M 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- QOPBTFMUVTXWFF-UHFFFAOYSA-N tripropyl phosphite Chemical group CCCOP(OCCC)OCCC QOPBTFMUVTXWFF-UHFFFAOYSA-N 0.000 description 1
- YJLVKRVGSARISS-UHFFFAOYSA-N tris(2,6-dimethylphenyl) phosphite Chemical group CC1=CC=CC(C)=C1OP(OC=1C(=CC=CC=1C)C)OC1=C(C)C=CC=C1C YJLVKRVGSARISS-UHFFFAOYSA-N 0.000 description 1
- RERMPCBBVZEPBS-UHFFFAOYSA-N tris(2,6-dimethylphenyl)phosphane Chemical compound CC1=CC=CC(C)=C1P(C=1C(=CC=CC=1C)C)C1=C(C)C=CC=C1C RERMPCBBVZEPBS-UHFFFAOYSA-N 0.000 description 1
- WXAZIUYTQHYBFW-UHFFFAOYSA-N tris(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 WXAZIUYTQHYBFW-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- XHGIFBQQEGRTPB-UHFFFAOYSA-N tris(prop-2-enyl) phosphate Chemical compound C=CCOP(=O)(OCC=C)OCC=C XHGIFBQQEGRTPB-UHFFFAOYSA-N 0.000 description 1
- IZYFBZDLXRHRLF-UHFFFAOYSA-N tritylphosphane;hydroiodide Chemical group [I-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 IZYFBZDLXRHRLF-UHFFFAOYSA-N 0.000 description 1
- PPQRADLPLZYEKN-UHFFFAOYSA-N tritylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 PPQRADLPLZYEKN-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with 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
- C07D307/32—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
〔1〕式(1)
で示されるβ−ジヒドロフラン誘導化合物。
で示されるジオール化合物に二炭酸ジアルキルを作用させることを特徴とする、式(1)または式(4)
で示されるβ−ジヒドロフラン誘導化合物またはβ−テトラヒドロフラン誘導化合物の製造方法。
で表わされるβ−ジヒドロフラン誘導化合物に遷移金属触媒の存在下、置換されていてもよいウラシル、チミン、アミノ基がt−ブトキシカルボニル基、ベンジルオキシカルボニル基、9−フルオレニルメチルオキシカルボニル基、2,2,2−トリクロロエトキシカルボニル基、アリルオキシカルボニル基、トリフルオロアセチル基、フタロイル基、p−トルエンスルホニル基、及び2−ニトロベンゼンスルホニル基から選択される保護基で保護されていてもよいシトシン、イミダゾール、ベンゾイミダゾール、ベンゾ−1,2,3−トリアゾール、置換されていてもよいチオウラシル及び置換されていてもよいプリンから選ばれる求核剤を反応させることを特徴とする式(5)
で表わされるβ−グリコシド化合物の製造方法。
本発明の製造方法の出発物質である式(2)または(3)で表されるジオール化合物のうち、式(6)
ヒドロキシ基およびメルカプト基の保護基としては、メチル基、ベンジル基、p−メトキシベンジル基、t−ブチル基等のアルキル系保護基、メトキシメチル基、2−テトラヒドロピラニル基、エトキシエチル基等のアセタール系保護基、アセチル基、ピバロイル基、ベンゾイル基等のアシル系保護基、トリメチルシリル基、トリエチルシリル基、t−ブチルジメチルシリル基、トリイソプロピルシリル基、t−ブチルジフェニルシリル基等のシリル系保護基等が挙げられる。
本発明の式(1)で表されるβ−ジヒドロフラン誘導化合物および式(4)で表されるβ−テトラヒドロフラン誘導化合物の製造方法を下記スキームに示す。
ベンジルオキシカルボニルクロリド、1−フェネチルオキシカルボニルクロリド、2−フェネチルオキシカルボニルクロリド、
メチルアミノカルボニルクロリド、エチルアミノカルボニルクロリド、n−プロピルアミノカルボニルクロリド、i−プロピルアミノカルボニルクロリド、c−プロピルアミノカルボニルクロリド、n−ブチルアミノカルボニルクロリド、i−ブチルアミノカルボニルクロリド、s−ブチルアミノカルボニルクロリド、t−ブチルアミノカルボニルクロリド、c−ブチルアミノカルボニルクロリド、n−ペンチルアミノカルボニルクロリド、n−ヘプチルアミノカルボニルクロリド、n−オクチルアミノカルボニルクロリド、n−ノニルアミノカルボニルクロリド、n−デシルアミノカルボニルクロリド、ジメチルアミノカルボニルクロリド、ジエチルアミノカルボニルクロリド、ジ−n−プロピルアミノカルボニルクロリド、ジ−i−プロピルアミノカルボニルクロリド、ジ−c−プロピルアミノカルボニルクロリド、ジ−n−ブチルアミノカルボニルクロリド、ジ−i−ブチルアミノカルボニルクロリド、ジ−s−ブチルアミノカルボニルクロリド、ジ−c−ブチルアミノカルボニルクロリド、ジ−n−ペンチルアミノカルボニルクロリド、ジ−n−ヘプチルアミノカルボニルクロリド、ジ−n−オクチルアミノカルボニルクロリド、ジ−n−ノニルアミノカルボニルクロリド、ジ−n−デシルアミノカルボニルクロリド、メチルエチルアミノカルボニルクロリド、メチル−n−プロピルアミノカルボニルクロリド、メチル−n−ブチルアミノカルボニルクロリド、
ジメチルホスホリルクロリド、ジエチルホスホリルクロリド、ジ−n−プロピルホスホリルクロリド、ジ−i−プロピルホスホリルクロリド、ジ−c−プロピルホスホリルクロリド、ジ−n−ブチルホスホリルクロリド、ジ−i−ブチルホスホリルクロリド、ジ−s−ブチルホスホリルクロリド、ジ−t−ブチルホスホリルクロリド、ジ−c−ブチルホスホリルクロリド、ジ−n−ペンチルホスホリルクロリド、ジ−(1−メチル−n−ブチル)ホスホリルクロリド、ジ−(2−メチル−n−ブチル)ホスホリルクロリド、ジ−(3−メチル−n−ブチル)ホスホリルクロリド、ジ−(1,1−ジメチル−n−プロピル)ホスホリルクロリド、ジ−c−ペンチルホスホリルクロリド、ジ−(2−メチル−c−ブチル)ホスホリルクロリド、ジ−n−ヘキシルホスホリルクロリド、ジ−(1−メチル−n−ペンチル)ホスホリルクロリド、ジ−(2−メチル−n−ペンチル)ホスホリルクロリド、ジ−(1,1−ジメチル−n−ブチル)ホスホリルクロリド、ジ−(1−エチル−n−ブチル)ホスホリルクロリド、ジ−(1,1,2−トリメチル−n−プロピル)ホスホリルクロリド、ジ−c−ヘキシルホスホリルクロリド、ジ−(1−メチル−c−ペンチル)ホスホリルクロリド、ジ−(1−エチル−c−ブチル)ホスホリルクロリド、ジ−(1,2−ジメチル−c−ブチル)ホスホリルクロリド、
ジフェニルホスホリルクロリド、ジ−o−メチルフェニルホスホリルクロリド、ジ−m−メチルフェニルホスホリルクロリド、ジ−p−メチルフェニルホスホリルクロリド、ジ−o−トリフルオロメチルフェニルホスホリルクロリド、ジ−m−トリフルオロメチルフェニルホスホリルクロリド、ジ−p−トリフルオロメチルフェニルホスホリルクロリド、ジ−p−エチルフェニルホスホリルクロリド、ジ−p−i−プロピルフェニルホスホリルクロリド、ジ−p−t−ブチルフェニルホスホリルクロリド、ジ−o−クロルフェニルホスホリルクロリド、ジ−m−クロルフェニルホスホリルクロリド、ジ−p−クロルフェニルホスホリルクロリド、ジ−o−ブロモフェニルホスホリルクロリド、ジ−m−ブロモフェニルホスホリルクロリド、ジ−p−ブロモフェニルホスホリルクロリド、ジ−o−フルオロフェニルホスホリルクロリド、ジ−p−フルオロフェニルホスホリルクロリド、ジ−o−メトキシフェニルホスホリルクロリド、ジ−p−メトキシフェニルホスホリルクロリド、ジ−o−トリフルオロメトキシフェニルホスホリルクロリド、ジ−p−トリフルオロメトキシフェニルホスホリルクロリド、ジ−p−ニトロフェニルホスホリルクロリド、ジ−p−シアノフェニルホスホリルクロリド、ジ−3,5−ジメチルフェニルホスホリルクロリド、ジ−3,5−ビストリフルオロメチルフェニルホスホリルクロリド、ジ−3,5−ジメトキシフェニルホスホリルクロリド、ジ−3,5−ビストリフルオロメトキシフェニルホスホリルクロリド、ジ−3,5−ジエチルフェニルホスホリルクロリド、ジ−3,5−ジ−i−プロピルフェニルホスホリルクロリド、ジ−3,5−ジクロルフェニルホスホリルクロリド、ジ−3,5−ジブロモフェニルホスホリルクロリド、ジ−3,5−ジフルオロフェニルホスホリルクロリド、ジ−3,5−ジニトロフェニルホスホリルクロリド、ジ−3,5−ジシアノフェニルホスホリルクロリド、ジ−2,4,6−トリメチルフェニルホスホリルクロリド、ジ−2,4,6−トリストリフルオロメチルフェニルホスホリルクロリド、ジ−2,4,6−トリメトキシフェニルホスホリルクロリド、ジ−2,4,6−トリストリフルオロメトキシフェニルホスホリルクロリド、ジ−2,4,6−トリクロルフェニルホスホリルクロリド、ジ−2,4,6−トリブロモフェニルホスホリルクロリド、ジ−2,4,6−トリフルオロフェニルホスホリルクロリド、ジ−α−ナフチルホスホリルクロリド、ジ−β−ナフチルホスホリルクロリド、ジ−o−ビフェニリルホスホリルクロリド、ジ−m−ビフェニリルホスホリルクロリド、ジ−p−ビフェニリルホスホリルクロリド等が挙げられる。
鉄触媒としては、ペンタカルボニル鉄、エニアカルボニル二鉄、ドデカカルボニル三鉄、ジクロロビス(トリフェニルホスフィン)鉄、テトラカルボニル(トリフェニルホスフィン)鉄、トリカルボニルビス(トリフェニルホスフィン)鉄、シクロペンタジエニルジカルボニル鉄ナトリウム、シクロペンタジエニルジカルボニル鉄ダイマー、ペンタメチルシクロペンタジエニルジカルボニル鉄ダイマー、シクロペンタジエントリカルボニル鉄、シクロヘキサジエントリカルボニル鉄、ブタジエントリカルボニル鉄、テトラカルボニル鉄酸ナトリウム、ビス(シクロペンタジエニル)鉄(フェロセン)、ビス(テトラメチルシクロペンタジエニル)鉄、ビス(メチルシクロペンタジエニル)鉄(1,1’−ジメチルフェロセン)、トリカルボニル(ニトロソ)鉄ナトリウム、トリカルボニル(ニトロシル)鉄テトラブチルアンモニウム、アセチルフェロセン、アセチルアセトナト鉄等の錯体触媒類が挙げられる。
機種:JNM−ECP300(JEOL製)(300MHz)
測定溶媒:CDCl3、CD3OD
[2]LC
LC条件例:
・Column:Capcellpak C18 MGII 4.6*100mm 3μm
・Oven Temp:40℃
・Eluent:CH3CN,H2O
CH3CN=20%(0min.)→80%(15min.)
・Flow rate:1.2mL/min.
・Detector:UV254nm
(5R)−2−ヒドロキシ−5−ヒドロキシメチル−5−(2−トリメチルシリルエチニル)−2,5−ジヒドロフランの製造
窒素置換したガラス製反応容器にテトラヒドロフラン2700mLと水300mLを入れて攪拌したところに、炭酸水素ナトリウム343gと酢酸ナトリウム167gを加えた。−15℃に冷却した反応液に、N−ブロモスクシンイミド376gとフルフリルアルコール200gを滴下し、−15℃で10分攪拌した。その後反応液に4−ジメチルアミノピリジン50gと無水酢酸416gを加えて室温まで昇温し3時間攪拌した。反応液を5℃以下に冷却し、10N水酸化ナトリウム水溶液200mLと2N水酸化ナトリウム760mLを加えてpH6.5に調整した。酢酸エチル1500mLを加えて攪拌後、分液させた有機層に炭酸水素ナトリウムの飽和水溶液1500mLを加えて攪拌し分液した。有機層を減圧濃縮し、279g(収率73%)の2−アセチルオキシ−5,6−ジヒドロ−2H−ピラノ−5−オンを得た。
式(A)で表される(2S,5R)−5−t−ブトキシカルボニルオキシメチル−5−(2−トリメチルシリルエチニル)−2−t−ブトキシカルボニルオキシ−2,5−ジヒドロフランの製造
式(B)で表される(2R,5R)−5−t−ブトキシカルボニルオキシメチル−5−(2−トリメチルシリルエチニル)−2−(チミン−1−イル)−2,5−ジヒドロフランの製造
式(C)で表される4’−エチニル−2’,3’−ジデヒドロ−3’−デオキシチミジンの製造
式(D)で表される(2S,5R)−5−t−ブトキシカルボニルオキシメチル−5−エチニル−2−t−ブトキシカルボニルオキシ−2,5−ジヒドロフランの製造
式(E)で表される(2R,5R)−5−t−ブトキシカルボニルオキシメチル−5−エチニル−2−(チミン−1−イル)−2,5−ジヒドロフランの製造
式(C)で表される4’−エチニル−2’,3’−ジデヒドロ−3’−デオキシチミジンの製造
Claims (4)
- 式(1)
で示されるβ−ジヒドロフラン誘導化合物。 - 式(2)または式(3)
で示されるジオール化合物に二炭酸ジアルキルを作用させることを特徴とする、式(1)または式(4)
で示されるβ−ジヒドロフラン誘導化合物またはβ−テトラヒドロフラン誘導化合物の製造方法。 - 式(1)
で表わされるβ−ジヒドロフラン誘導化合物に遷移金属触媒の存在下、置換されていてもよいウラシル、チミン、アミノ基がt−ブトキシカルボニル基、ベンジルオキシカルボニル基、9−フルオレニルメチルオキシカルボニル基、2,2,2−トリクロロエトキシカルボニル基、アリルオキシカルボニル基、トリフルオロアセチル基、フタロイル基、p−トルエンスルホニル基、及び2−ニトロベンゼンスルホニル基から選択される保護基で保護されていてもよいシトシン、イミダゾール、ベンゾイミダゾール、ベンゾ−1,2,3−トリアゾール、置換されていてもよいチオウラシル及び置換されていてもよいプリンから選ばれる求核剤を反応させることを特徴とする式(5)
で表わされるβ−グリコシド化合物の製造方法。 - 前記求核剤がチミンである請求項3に記載のβ−グリコシド化合物の製造方法。
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PCT/JP2011/052508 WO2011099443A1 (ja) | 2010-02-15 | 2011-02-07 | β-ジヒドロフラン誘導化合物、β-ジヒドロフラン誘導化合物またはβ-テトラヒドロフラン誘導化合物の製造方法、β-グリコシド化合物、β-グリコシド化合物の製造方法、並びに、4'-エチニルd4T及びその類縁化合物の製造方法 |
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CN102741237A (zh) | 2012-10-17 |
WO2011099443A1 (ja) | 2011-08-18 |
CN102741237B (zh) | 2015-04-29 |
EP2537839B1 (en) | 2016-12-14 |
EP2537839A1 (en) | 2012-12-26 |
JPWO2011099443A1 (ja) | 2013-06-13 |
US9212174B2 (en) | 2015-12-15 |
EP2537839A4 (en) | 2013-07-10 |
KR20130008547A (ko) | 2013-01-22 |
US20120322995A1 (en) | 2012-12-20 |
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