JP2005239680A - Fluorine-containing unsaturated lipid derivative - Google Patents
Fluorine-containing unsaturated lipid derivative Download PDFInfo
- Publication number
- JP2005239680A JP2005239680A JP2004054622A JP2004054622A JP2005239680A JP 2005239680 A JP2005239680 A JP 2005239680A JP 2004054622 A JP2004054622 A JP 2004054622A JP 2004054622 A JP2004054622 A JP 2004054622A JP 2005239680 A JP2005239680 A JP 2005239680A
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- JP
- Japan
- Prior art keywords
- group
- compound
- fluorine
- added
- solution
- 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.)
- Granted
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- 229910052731 fluorine Inorganic materials 0.000 title claims abstract description 27
- 150000002632 lipids Chemical class 0.000 title claims abstract description 16
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 title abstract description 19
- 239000011737 fluorine Substances 0.000 title abstract description 19
- 125000000962 organic group Chemical group 0.000 claims abstract description 31
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 10
- 229910052751 metal Inorganic materials 0.000 claims abstract description 8
- 239000002184 metal Substances 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 125000004437 phosphorous atom Chemical group 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 16
- 150000001298 alcohols Chemical class 0.000 abstract description 3
- 125000004429 atom Chemical group 0.000 abstract description 3
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 abstract description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- 239000000243 solution Substances 0.000 description 43
- 150000001875 compounds Chemical class 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 36
- 238000003786 synthesis reaction Methods 0.000 description 36
- 239000002904 solvent Substances 0.000 description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- 238000001914 filtration Methods 0.000 description 25
- 239000000203 mixture Substances 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- -1 glycerol saturated Chemical class 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- TXEBWPPWSVMYOA-UHFFFAOYSA-N 4-[3-[(1-amino-2-chloroethyl)amino]propyl]-1-[[3-(2-chlorophenyl)phenyl]methyl]-5-hydroxyimidazolidin-2-one Chemical compound NC(CCl)NCCCC1NC(=O)N(Cc2cccc(c2)-c2ccccc2Cl)C1O TXEBWPPWSVMYOA-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229940126657 Compound 17 Drugs 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000003810 Jones reagent Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 229940126142 compound 16 Drugs 0.000 description 4
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 229920001542 oligosaccharide Polymers 0.000 description 4
- 150000002482 oligosaccharides Chemical class 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 4
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- NYKRTKYIPKOPLK-UHFFFAOYSA-N 1-bromo-2-dichlorophosphoryloxyethane Chemical compound ClP(Cl)(=O)OCCBr NYKRTKYIPKOPLK-UHFFFAOYSA-N 0.000 description 3
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000002253 acid Substances 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 125000006165 cyclic alkyl group Chemical group 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 150000001993 dienes Chemical class 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 150000002314 glycerols Chemical class 0.000 description 3
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical group NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 2
- ACIAHEMYLLBZOI-ZZXKWVIFSA-N Unsaturated alcohol Chemical class CC\C(CO)=C/C ACIAHEMYLLBZOI-ZZXKWVIFSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- RNVYQYLELCKWAN-RXMQYKEDSA-N [(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@@H](CO)O1 RNVYQYLELCKWAN-RXMQYKEDSA-N 0.000 description 2
- RNVYQYLELCKWAN-YFKPBYRVSA-N [(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@H](CO)O1 RNVYQYLELCKWAN-YFKPBYRVSA-N 0.000 description 2
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl 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])[H] 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
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Abstract
Description
本発明は、新規な含フッ素脂質誘導体に関するものである。 The present invention relates to a novel fluorine-containing lipid derivative.
飽和・不飽和脂肪酸などの脂質、グリセロール1分子と2分子の飽和または不飽和脂肪酸によりエステル結合した脂質は界面活性性を有し、採鉱、金属加工、表面仕上げ、及び洗浄用などに使用される各種工業用処理剤、家庭用の各種洗浄剤及び各種清浄剤、医薬品、化粧品や食品用の添加剤などとして広く使用されている。これらの用途の中でも、特に乳化剤、解乳化剤、洗浄剤、分散剤およびヒドロトロープ剤等として有用なものとされている。 Lipids such as saturated and unsaturated fatty acids, and lipids esterified with one and two glycerol saturated or unsaturated fatty acids have surface activity and are used for mining, metalworking, surface finishing, and cleaning. It is widely used as various industrial treatment agents, household cleaning agents and detergents, pharmaceuticals, cosmetics and food additives. Among these uses, they are particularly useful as emulsifiers, demulsifiers, detergents, dispersants, hydrotropes and the like.
従来、この種の不飽和脂肪酸のグリセロールエステルでは、グリセロール1分子と2分子の飽和または不飽和脂肪酸がエステル結合させて、残りの水酸基にリン酸基が結合した非環状のリン脂質化合物が生体内および人為的手段により合成されてきた。これらの物質は、その特性を改善すべく検討が進められている。これらの中で環状の部分を有する場合については、分子剛性の特性が改善されることが考えられ、環状リン脂質の合成が行われている。
また、フッ素原子の導入は、その撥水性を使用した表面改良材として利用されている。さらに炭素−フッ素結合が炭素−水素結合より強固(ブロック効果)であるため、フッ素原子の導入は化合物の安定性を増大させる。フッ素原子は、水素原子とほぼ同じファンデルワールス半径を有する(ミミック効果)ことから構造変化を伴わずに化合物の物性変化をもたらすことができる。
Conventionally, in this type of unsaturated fatty acid glycerol ester, an acyclic phospholipid compound in which one molecule of glycerol and two molecules of saturated or unsaturated fatty acid are ester-bonded and the remaining hydroxyl group is bonded to a phosphate group in vivo. And have been synthesized by human means. These materials are under investigation to improve their properties. Among these, in the case of having a cyclic portion, it is considered that the characteristics of molecular rigidity are improved, and synthesis of cyclic phospholipids is performed.
The introduction of fluorine atoms is used as a surface improvement material using its water repellency. Furthermore, since the carbon-fluorine bond is stronger (block effect) than the carbon-hydrogen bond, introduction of fluorine atoms increases the stability of the compound. Since the fluorine atom has almost the same van der Waals radius as the hydrogen atom (mimic effect), the physical property of the compound can be changed without a structural change.
Vierlingらは、フッ素化したグリセロリン脂質の合成について報告している。グリセロールとフッ素化した不飽和アルコール体およびエステル体とを結合させ、さらに親水基としてホスホコリン基またはホスホエタノールアミン基またはホスホエタノールアミンのポリエチレングリコール(メチルエーテル末端)の導入に成功している。グリセロリン脂質の不飽和は、エーテル体ではエンとジエン、エステル体ではエンのみの合成が報告されている(非特許文献1,2参照)。ところが、これらの化合物はすべてグリセロールの2級水酸基がラセミ体(R体とS体の混合物)であり、キラルなグリセロールのエーテル体およびエステル体を得るには至っていない。さらにジエンのエステル体および三重結合を有するフッ素誘導体の合成は行っていない。 Vierling et al. Report the synthesis of fluorinated glycerophospholipids. Glycerol has been combined with fluorinated unsaturated alcohols and esters, and a phosphocholine group, phosphoethanolamine group, or polyethylene glycol (methyl ether end) of phosphoethanolamine has been successfully introduced as a hydrophilic group. As for the unsaturation of glycerophospholipid, synthesis of only ene and diene in the ether form and only ene in the ester form has been reported (see Non-Patent Documents 1 and 2). However, in these compounds, the secondary hydroxyl group of glycerol is a racemic form (mixture of R and S forms), and chiral ethers and esters of glycerol have not been obtained. Furthermore, synthesis of ester derivatives of diene and fluorine derivatives having a triple bond have not been carried out.
また、Luらは、Rf−C≡C−RとRf−(CH=CH)2−Rの合成に成功している。その事例として、RfはCl(CF2)n(n=2,4,8)とCF3とC2F5、Rはn−CnHm(n,m=3,7;5,11;6,13;8,17)と(CH2)nOH(n=6,9)を組合せた化合物のみが報告されている(非特許文献3参照)。しかし、Z体の合成および親水性基の導入、グリセロール誘導体の合成は行っていない。 Lu et al. Have succeeded in synthesizing Rf—C≡C—R and Rf— (CH═CH) 2 —R. As an example, Rf is Cl (CF 2 ) n (n = 2, 4, 8), CF 3 and C 2 F 5 , R is n-C n H m (n, m = 3, 7; 5, 11 Only 6,6,13; 8,17) and (CH 2 ) n OH (n = 6, 9) have been reported (see Non-Patent Document 3). However, synthesis of Z-form, introduction of hydrophilic groups, and synthesis of glycerol derivatives are not performed.
また、Prestwichは、一部をフッ素化した(Z)−5−デセニルアセテートを合成し、また三重結合の導入にも成功しているものの、炭素数10個の化合物に限定されており、さらに水酸基には脱保護可能な官能基(アセチル基またはメトキシメチル基またはt−ブチルメチルシリル基)の導入のみである(非特許文献4参照)。E体の合成および親水性基の導入、グリセロール誘導体の合成は行っていない。
Buchananらは、一部をフッ素化した(Z)−11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,18−ヘプタデカフルオロ−オクタデカ−8−エノイック酸とそのアルコール体の合成を報告している。その水酸基には脱保護可能なテトラヒドロピラニル基の導入のみが報告されている(非特許文献5参照)。しかし、三重結合体の合成、E体の合成、親水性基の導入、グリセロール誘導体の合成には至っていない。
In addition, Prestwich has synthesized (Z) -5-decenyl acetate partially fluorinated and has succeeded in introducing a triple bond, but is limited to a compound having 10 carbon atoms. Furthermore, only the introduction of a deprotectable functional group (acetyl group, methoxymethyl group or t-butylmethylsilyl group) into the hydroxyl group (see Non-Patent Document 4). Synthesis of E-form, introduction of hydrophilic group, and synthesis of glycerol derivative were not performed.
Buchanan et al. (Z) -11, 11, 12, 12, 13, 13, 14, 14, 15, 15, 16, 16, 17, 17, 18, 18-heptadecafluoro- partially fluorinated The synthesis of octadec-8-enoic acid and its alcohol is reported. Only the introduction of a deprotectable tetrahydropyranyl group has been reported for the hydroxyl group (see Non-Patent Document 5). However, the synthesis of triple bonds, synthesis of E isomers, introduction of hydrophilic groups, and synthesis of glycerol derivatives have not been achieved.
本発明は、従来の技術における上記した実状に鑑みてなされたものである。すなわち、本発明の目的は、エン(CH=CH)、イン(C≡C)もしくはジエン((CH=CH)2)という炭素ー炭素不飽和結合を有する含フッ素アルコール誘導体、またはキラルなグリセロール1分子と2個のエステル結合もしくはエーテル結合により結合されて得られる新規な含フッ素不飽和脂質誘導体を提供することにある。 This invention is made | formed in view of the above-mentioned actual condition in a prior art. That is, an object of the present invention is to provide a fluorine-containing alcohol derivative having a carbon-carbon unsaturated bond of ene (CH═CH), in (C≡C) or diene ((CH═CH) 2 ), or chiral glycerol 1 The object is to provide a novel fluorine-containing unsaturated lipid derivative obtained by linking a molecule with two ester bonds or ether bonds.
本発明者らは、前記課題について鋭意研究を重ねた結果、含フッ素不飽和アルコール誘導体を合成できることを見出し、さらに、これらの含フッ素不飽和アルコール誘導体もしくは酸化により得られたカルボン酸またはその誘導体とグリセロールを反応させると、グリセロールが2個のエステルもしくはエーテル結合した新規な含フッ素不飽和脂質誘導体を合成できることを見出した。また、その際、原料物質として、キラルな化合物である示性式HOCH2CH(OH)CH2OHで示される化合物を用いると、キラルな化合物群を選択的に製造できることを知見し、本発明を完成させるに至った。つまり、本発明では、キラルなグリセロールまたはグリセロールの1位もしくは2位、または1位と2位の水酸基を保護したものを光学分割もしくは酵素を用いた分割により得たもの、または、(S)−(+)−2,2―ジメチル−1,3―ジオキソラン−4−メタノールもしくは(R)−(―)−2,2―ジメチル−1,3―ジオキソラン−4−メタノール、または、(R)−(+)−3―ベンジロキシ−1,2―プロパンジオールもしくは(S)−(−)−3―ベンジロキシ−1,2―プロパンジオールを用いるものである。 As a result of intensive studies on the above problems, the present inventors have found that fluorine-containing unsaturated alcohol derivatives can be synthesized. Further, these fluorine-containing unsaturated alcohol derivatives or carboxylic acids obtained by oxidation or derivatives thereof It has been found that when glycerol is reacted, a novel fluorine-containing unsaturated lipid derivative in which glycerol is linked to two esters or ethers can be synthesized. Further, at that time, it was found that a chiral compound group can be selectively produced by using a compound represented by the sexual formula HOCH 2 CH (OH) CH 2 OH, which is a chiral compound, as a raw material, and the present invention. It came to complete. That is, in the present invention, chiral glycerol or glycerol having a hydroxyl group at the 1-position or 2-position, or the 1-position and 2-position protected is obtained by optical resolution or resolution using an enzyme, or (S)- (+)-2,2-dimethyl-1,3-dioxolane-4-methanol or (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol or (R)- (+)-3-Benzyloxy-1,2-propanediol or (S)-(−)-3-benzyloxy-1,2-propanediol is used.
すなわち、本発明によれば、下記1.〜5.に示す含フッ素脂質誘導体が提供される。
1.一般式(1)
1. General formula (1)
2.一般式(2)
3.一般式(3)
4.一般式(4)
5.一般式(5)
及びR2は、少なくとも1方がフッ素原子を含む有機基である。R6は親水性の有機基であるか、またはリン原子を含む基もしくは硫黄原子を含む基を介して結合した有機基を示す。)で表される含フッ素脂質誘導体。
5). General formula (5)
And R 2 is an organic group at least one of which contains a fluorine atom. R 6 represents a hydrophilic organic group or an organic group bonded via a group containing a phosphorus atom or a group containing a sulfur atom. ) -Containing fluorinated lipid derivative.
本発明は、同一分子内に含フッ素有機基とキラルなグリセロールがエステル結合またはエーテル結合した新規化合物を提供するものである。これらの化合物は、界面活性性を有するものであり、産業界および家庭における、例えば、金属加工、採鉱、表面仕上げ、洗浄や清浄、化粧品、医薬、食品加工及び調理などの分野において、殊に乳化剤、解乳化剤、洗浄剤、分散剤あるいはヒドロトロープ剤として用いることができる。 The present invention provides a novel compound in which a fluorine-containing organic group and chiral glycerol are ester-bonded or ether-bonded in the same molecule. These compounds are surface-active and are used as emulsifiers in industry and household, for example in the fields of metalworking, mining, surface finishing, cleaning and cleaning, cosmetics, medicine, food processing and cooking. , Demulsifiers, detergents, dispersants or hydrotropes.
本発明の前記一般式(1)〜(5)で表される含フッ素不飽和脂質誘導体において、まず基R1〜R6ついて、その内容を具体的に説明する。
基R1〜R4は、それぞれ有機基であるが、その中で、R1とR3は、少なくとも1方がフッ素原子を含む有機基である。またR1とR3、R2とR4は、それぞれ同一であっても異なっていても良い。また、基R5は水素原子、金属元素もしくは有機基であるか、またはリン原子を含む基もしくは硫黄原子を含む基を介して結合した有機基である。R6は親水性の有機基であるか、またはリン原子を含む基もしくは硫黄原子を含む基を介して結合した有機基である。その中のリン原子を含む基としては、P、PO、PO2、PO3などが含まれる。また、硫黄原子を含む基としては、S、SO、SO2などが含まれる。
In the fluorine-containing unsaturated lipid derivative represented by the general formulas (1) to (5) of the present invention, the contents of the groups R 1 to R 6 will be specifically described first.
The groups R 1 to R 4 are each an organic group. Among them, R 1 and R 3 are organic groups in which at least one of them contains a fluorine atom. R 1 and R 3 , R 2 and R 4 may be the same or different. The group R 5 is a hydrogen atom, a metal element or an organic group, or an organic group bonded through a group containing a phosphorus atom or a group containing a sulfur atom. R 6 is a hydrophilic organic group or an organic group bonded through a group containing a phosphorus atom or a group containing a sulfur atom. Among them, the group containing a phosphorus atom includes P, PO, PO 2 , PO 3 and the like. Examples of the group containing a sulfur atom include S, SO, SO 2 and the like.
次に、X1及びX2は、同一であっても異なっていても良く、それぞれC≡C、CH=CH及び(CH=CH)2から選ばれる不飽和炭化水素基である。また、Yはカルボニル基であって、そのカルボニル基の個数を示すnは、0または1である。 X 1 and X 2 may be the same or different and are each an unsaturated hydrocarbon group selected from C≡C, CH═CH and (CH═CH) 2 . Y is a carbonyl group, and n indicating the number of carbonyl groups is 0 or 1.
前記有機基としては、(1)アルキル基、(2)環状アルキル基、(3)アリール基、(4)アラルキル基からなる基から選ばれるものであることが好ましい。また、親水性とは、有機基に水酸基、カルボン酸またはその金属塩(Na、K、Mgなど)、リン酸基、スルホン酸基またはそれらの金属塩(Na、K、Mgなど)などが結合しているものである。
以下、これらの基について、さらに詳細に説明する。
The organic group is preferably selected from the group consisting of (1) an alkyl group, (2) a cyclic alkyl group, (3) an aryl group, and (4) an aralkyl group. In addition, hydrophilicity means that a hydroxyl group, a carboxylic acid or a metal salt thereof (Na, K, Mg, etc.), a phosphate group, a sulfonic acid group or a metal salt thereof (Na, K, Mg, etc.) is bonded to an organic group It is what you are doing.
Hereinafter, these groups will be described in more detail.
(1)アルキル基については以下のとおりである。アルキル基は、直鎖あるいは分岐状アルキル基から選ばれる基である。その炭素数は、通常100個以下、好ましくは72個以下、さらに好ましくは32個以下であり、具体的には、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、sec−ブチル基、t−ブチル基、n−ペンチル基、イソペンチル基、2−メチルブチル基、1−メチルブチル基、n−ヘキシル基、イソヘキシル基、3−メチルペンチル基、2−メチルペンチル基、1−メチルペンチル基、ヘプチル基、オクチル基、イソオクチル基、2−エチルヘキシル基、ノニル基、デシル基、ウンデシル基、ドデシル基、テトラデシル基、ヘキサデシル基、オクタデシル基、エイコシル基等を挙げることができる。
(2)環状アルキル基としては、シクロペンチル基、シクロヘキシル基、アダマンチル基等を挙げることができる。
(3)アリール基としては、フエニル基、ナフタレン基等を挙げることができる。
(4)アラルキル基としては、ベンジル基、フェネチル基等を挙げることができる。
(1) The alkyl group is as follows. The alkyl group is a group selected from linear or branched alkyl groups. The number of carbon atoms is usually 100 or less, preferably 72 or less, more preferably 32 or less. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group. Group, sec-butyl group, t-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, 1-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, 2-methylpentyl group, Examples include 1-methylpentyl group, heptyl group, octyl group, isooctyl group, 2-ethylhexyl group, nonyl group, decyl group, undecyl group, dodecyl group, tetradecyl group, hexadecyl group, octadecyl group, eicosyl group and the like.
(2) Examples of the cyclic alkyl group include a cyclopentyl group, a cyclohexyl group, and an adamantyl group.
(3) Examples of the aryl group include a phenyl group and a naphthalene group.
(4) Examples of the aralkyl group include a benzyl group and a phenethyl group.
前記のアルキル基、環状アルキル基、アリール基又はアラルキル基に置換していても良い置換基としては、本発明の化合物を製造する際に、製造反応に関与しない基であれば差し支えない。置換あるいは未置換アリール基、カルボニル基、アルコキシ基、アルコキシカルボニル基、アシル基、アシルオキシ基、アルキルまたはアリールスルホニル基、ニトロ基、ハロゲン等が例示される。酸素原子、窒素原子、硫黄原子などが結合を介しても良い(ポリエチレングリコールなど)。 The substituent that may be substituted with the alkyl group, cyclic alkyl group, aryl group, or aralkyl group may be any group that does not participate in the production reaction when the compound of the present invention is produced. Examples include substituted or unsubstituted aryl groups, carbonyl groups, alkoxy groups, alkoxycarbonyl groups, acyl groups, acyloxy groups, alkyl or arylsulfonyl groups, nitro groups, halogens, and the like. An oxygen atom, a nitrogen atom, a sulfur atom, or the like may be present through a bond (such as polyethylene glycol).
ハロゲン原子としては、フッ素原子、塩素原子、臭素原子、よう素原子を挙げることができる、有機基に置換した状態であってもよい。金属原子としては、リチウム、ナトリウム、カリウム、ルビジウム、セシウムなどのアルカリ金属、ベリリウム、マグネシウム、カルシウム、ストロンチウム、バリウムなどのアルカリ土類金属、ホウ素、アルミニウム、チタン、錫、鉄などの金属原子を挙げることができる。有機基がこれらを介して含まれていてもよい。 Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. The halogen atom may be substituted with an organic group. Examples of metal atoms include alkali metals such as lithium, sodium, potassium, rubidium and cesium, alkaline earth metals such as beryllium, magnesium, calcium, strontium and barium, and metal atoms such as boron, aluminum, titanium, tin and iron. be able to. An organic group may be contained via these.
上記一般式中のR5とR6は、前記の(1)〜(4)から選ばれる基を含み、さらにその他に、(5)糖類、(6)アミン類、(7)アミノ酸類、(8)ペプチド類、(9)核酸からなる群から選ばれる基であっても良く、また、リン酸や硫酸などを介して有機基が結合していても良い。 R 5 and R 6 in the above general formula include groups selected from the above (1) to (4), and in addition, (5) saccharides, (6) amines, (7) amino acids, ( 8) Peptides, (9) Groups selected from the group consisting of nucleic acids may be used, and organic groups may be bonded via phosphoric acid or sulfuric acid.
有機基に関して、前記(1)〜(4)以外の基の場合について説明する。
(5)糖類としては特に制限はないが、通常は単糖類、オリゴ糖類である。単糖類としてペントース、ヘキソース、デオキシヘキソース、ヘプトース、アミノ糖が挙げられ、具体的にはアラビノース、リボース、キシロース、グルコース、ガラクトース、マンノース、フルクトース、ラムノース、フコース、ジギトキソース、チマロース、オレアンドロース、ジギタロース、アピオース、ハマメロース、ストレプトース、セドヘプチュロース、コリオース、グルコサミン、ガラクトサミン、2−デオキシ−2−メチルアミノグルコースなどが例示される。オリゴ糖類として非還元性オリゴ糖、還元性オリゴ糖が挙げられ、具体的にはショ糖、トレハロース、ゲンチアノース、ラフィノース、乳糖、セルビオース、麦芽糖、ゲンチオビオースなどが例示される。
Regarding the organic group, the case of a group other than the above (1) to (4) will be described.
(5) Although there is no restriction | limiting in particular as saccharides, Usually, they are a monosaccharide and an oligosaccharide. Examples of monosaccharides include pentose, hexose, deoxyhexose, heptose, and amino sugar. Examples include apiose, hamamelose, streptose, sedoheptulose, coliose, glucosamine, galactosamine, 2-deoxy-2-methylaminoglucose and the like. Examples of oligosaccharides include non-reducing oligosaccharides and reducing oligosaccharides, and specific examples include sucrose, trehalose, gentianose, raffinose, lactose, cerbiose, maltose, and gentiobiose.
(6)アミン類としては、通常含まれる炭素の炭素数50以下、酸素数20以下、窒素数30以下、硫黄数5以下のもの、好ましくは、炭素数35以下、酸素数5以下、窒素数15以下、硫黄数3以下のもの、より好ましくは、炭素数2〜20、酸素数3以下、窒素数2〜10、硫黄数1以下の範囲で構成されるものである。
アミン類としては、ハロゲン原子で置換されていても良く、そのハロゲン原子としてフッ素、塩素、臭素、ヨウ素が挙げられ、1個以上置換されていても良い。また、リン酸基とアミノアルコールが結合しても良い。アミノアルコールとしてコリン、エタノールアミン、セリンが挙げられる。
(6) As amines, the carbon number of carbon normally contained is 50 or less,
The amines may be substituted with a halogen atom. Examples of the halogen atom include fluorine, chlorine, bromine and iodine, and one or more may be substituted. Moreover, a phosphoric acid group and amino alcohol may couple | bond together. Examples of amino alcohol include choline, ethanolamine, and serine.
(7)アミノ酸類としては、具体的にはグリシン、アラニン、バリン、ロイシン、イソロイシン、セリン、トレオニン、アスパラギン酸、グルタミン酸、アスパラギン、グルタミン、リジン、オルニチン、アルギニン、ヒスチジン、ヒドロキシリジン、システイン、シスチン、メチオニン、フェニルアラニン、チロシン、トリプトファン、プロリン、4−ヒドロキシプロリン、トリコロミン酸、イボテン酸、キスカリン酸、カナバニン、カイニン酸、ドモイ酸、1−アミノシクロプロパンカルボン酸、2−(メチレンシクロプロピル)グリシン、ヒポグリシンA、3−シアノアラニン、アベナ酸、ムギネ酸、ミモシン、レボドパ、β−ヒドロキシ−γ−メチルフルタミン酸、5−ヒドロキシトリプトファン、パントテン酸、ラミニン、ベタシアニンなどが例示される。また、タウリンなどのスルホン酸基を有するアミン類なども挙げられる。 (7) Specific examples of amino acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, ornithine, arginine, histidine, hydroxylysine, cysteine, cystine, Methionine, phenylalanine, tyrosine, tryptophan, proline, 4-hydroxyproline, tricolomic acid, ibotenic acid, quisqualic acid, canavanine, kainic acid, domoic acid, 1-aminocyclopropanecarboxylic acid, 2- (methylenecyclopropyl) glycine, hypoglycine A, 3-cyanoalanine, avenaic acid, mugineic acid, mimosine, levodopa, β-hydroxy-γ-methylflutamic acid, 5-hydroxytryptophan, pantothenic acid, laminin, betacia Nin and the like are exemplified. Also included are amines having a sulfonic acid group such as taurine.
(8)ペプチド類としては、特に制限されるものではないが、通常含窒素ポリマーであって、2個以上のアミノ酸の重縮合化合物またはタンパク質、ミオグロビン、ヘモグロビンなどのポリペプチドなどが挙げられる。 (8) Peptides are not particularly limited, but are usually nitrogen-containing polymers, and include polycondensation compounds of two or more amino acids or polypeptides such as proteins, myoglobin, hemoglobin, and the like.
(9)核酸としては、ヌクレオシド、ヌクレオチド、もしくはヌクレオチド単位のポリマー鎖が挙げられる。ヌクレオシドは、シトシン、チミン、アデニン、グアニンの塩基と2−デオキシリボースまたはリボースの糖が結合したものが挙げられる。ヌクレオチドは、ヌクレオシドの糖にリン酸基が結合したものが挙げられる。チミンはウラシルでもよい。 (9) Nucleic acids include nucleosides, nucleotides, or polymer chains of nucleotide units. Nucleosides include those in which cytosine, thymine, adenine, guanine base and 2-deoxyribose or ribose sugar are linked. Nucleotides include those in which a phosphate group is bound to a nucleoside sugar. The thymine may be uracil.
また、前記一般式(1)〜(4)で表される化合物の立体配置は、グリセロールの2級水酸基に応じて表現することができる。すなわち、グリセロールの2級水酸基がR配置のものとS配置のものとで示される。 The steric configuration of the compounds represented by the general formulas (1) to (4) can be expressed according to the secondary hydroxyl group of glycerol. That is, the secondary hydroxyl group of glycerol is indicated by the R configuration and the S configuration.
本発明の化合物の製法については、中間体の合成例を含めた実施例などを挙げて具体的に説明するが、本発明はこれらの実施例などによって何ら限定されるものではない。なお、以下に示す化合物番号は、図1〜図3に示すものと同じである。 The production method of the compound of the present invention will be specifically described with reference to examples including synthesis examples of intermediates, but the present invention is not limited to these examples. The compound numbers shown below are the same as those shown in FIGS.
[化合物1の合成]
[化合物2の合成]
[化合物3の合成]
[化合物4の合成]
[化合物5の合成]
[化合物6の合成]
[化合物7の合成]
[化合物8の合成]
[化合物9の合成]
[化合物10a、10bの合成]
[化合物11aの合成]
[化合物11bの合成]
[化合物12aの合成]
[化合物12bの合成]
[化合物13の合成]
化合物13は1H−NMRおよび19F−NMRスペクトルにより同定した。その結果は以下の通りである。
1H−NMR(TMS、CDCl3−CD3OD):1.25−1.43(m、8H)、1.53−1.62(m、4H)、2.35(m、2H)、3.29(s、9H)、3.71(bs、2H)、3.84(q、J=6.7Hz、2H)、4.27(bs、2H)。
19F−NMR(CFCl3、CDCl3−CD3OD):−80.71(t、J=10.04Hz、3F)、−96.05(m、2F)、−121.1(m、2F)、−121.8(m、4F)、−122.5〜−122.7(m、4F)、−126.0(m、2F)。
Compound 13 was identified by 1 H-NMR and 19 F-NMR spectra. The results are as follows.
1 H-NMR (TMS, CDCl 3 -CD 3 OD): 1.25-1.43 (m, 8H), 1.53-1.62 (m, 4H), 2.35 (m, 2H), 3.29 (s, 9H), 3.71 (bs, 2H), 3.84 (q, J = 6.7 Hz, 2H), 4.27 (bs, 2H).
19 F-NMR (CFCl 3 , CDCl 3 -CD 3 OD): −80.71 (t, J = 10.04 Hz, 3F), −96.05 (m, 2F), −121.1 (m, 2F) ), -121.8 (m, 4F), -122.5 to -122.7 (m, 4F), -126.0 (m, 2F).
化合物17、18の合成
[化合物14aの合成]
[化合物14bの合成]
[化合物15の合成]
[化合物16の合成]
化合物16は1H−NMRおよび19F−NMRスペクトルにより同定した。その結果は以下の通りである。
1H−NMR(CDCl3,TMS):7.23(d、J=8.5Hz、2H)、6.87(d、J=8.5Hz、2H)、4.46(s、2H)、3.79(s、3H)、3.39−3.60(m、9H)、2.35(m、4H)、1.54−1.64(m、8H)、1.28−1.47(m、16H)。
19F−NMR(CDCl3、CFCl3):−80.64(t、J=9.71Hz、6F)、−95.58(m、4F)、−120.49(m、4F)、−121.88(m、8F)、−122.55〜−122.74(m、8F)、−126.03(m、4F)。
1 H-NMR (CDCl 3 , TMS): 7.23 (d, J = 8.5 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 4.46 (s, 2H), 3.79 (s, 3H), 3.39-3.60 (m, 9H), 2.35 (m, 4H), 1.54-1.64 (m, 8H), 1.28-1. 47 (m, 16H).
19 F-NMR (CDCl 3 , CFCl 3 ): −80.64 (t, J = 9.71 Hz, 6F), −95.58 (m, 4F), −120.49 (m, 4F), −121 .88 (m, 8F), −122.55 to −122.74 (m, 8F), −126.03 (m, 4F).
[化合物17の合成]
化合物17は1H−NMRおよび19F−NMRスペクトルにより同定した。その結果は以下の通りである。
1H−NMR(CDCl3,TMS):3.39−3.60(m、9H)、2.35(m、4H)、2.17(bs、2H)、1.54−1.64(m、8H)、1.28−1.47(m、16H)。
19F−NMR(CDCl3、CFCl3):−80.64(t、J=9.71Hz、6F)、−95.58(m、4F)、−120.49(m、4F)、−121.88(m、8F)、−122.55〜−122.74(m、8F)、−126.03(m、4F)。
1 H-NMR (CDCl 3 , TMS): 3.39-3.60 (m, 9H), 2.35 (m, 4H), 2.17 (bs, 2H), 1.54-1.64 ( m, 8H), 1.28-1.47 (m, 16H).
19 F-NMR (CDCl 3 , CFCl 3 ): −80.64 (t, J = 9.71 Hz, 6F), −95.58 (m, 4F), −120.49 (m, 4F), −121 .88 (m, 8F), −122.55 to −122.74 (m, 8F), −126.03 (m, 4F).
[化合物18の合成]
化合物18は1H−NMRおよび19F−NMRスペクトルにより同定した。その結果は以下の通りである。
1H−NMR(CDCl3,TMS):4.00−4.21(m、2H)、3.78(bs、2H)、3.25−3.65(m、9H)、3.09(s、9H)、2.35(m、4H)、1.54−1.64(m、8H)、1.28−1.47(m、16H)。
19F−NMR(CDCl3、CFCl3):−80.64(t、J=9.71Hz、6F)、−95.58(m、4F)、−120.49(m、4F)、−121.88(m、8F)、−122.55〜−122.74(m、8F)、−126.03(m、4F)。
1 H-NMR (CDCl 3 , TMS): 4.00-4.21 (m, 2H), 3.78 (bs, 2H), 3.25-3.65 (m, 9H), 3.09 ( s, 9H), 2.35 (m, 4H), 1.54-1.64 (m, 8H), 1.28-1.47 (m, 16H).
19 F-NMR (CDCl 3 , CFCl 3 ): −80.64 (t, J = 9.71 Hz, 6F), −95.58 (m, 4F), −120.49 (m, 4F), −121 .88 (m, 8F), −122.55 to −122.74 (m, 8F), −126.03 (m, 4F).
化合物20、21の合成
[化合物19の合成]
[化合物20の合成]
[化合物21の合成]
本発明の含フッ素脂質誘導体は、同一分子内に含フッ素有機基とエステル結合またはエーテル結合を持つ新規な化合物であって、界面活性性を有することから、広範な技術分野に用いられる界面活性剤などとして利用できるものである。 The fluorine-containing lipid derivative of the present invention is a novel compound having a fluorine-containing organic group and an ester bond or an ether bond in the same molecule, and has a surfactant, so that it is a surfactant used in a wide range of technical fields. It can be used as such.
Claims (5)
The following general formula (3)
は、少なくとも1個のフッ素原子を含む有機基である。R6は親水性の有機基であるか、またはリン原子を含む基もしくは硫黄原子を含む基を介して結合した有機基を示す。)で表される含フッ素脂質誘導体。
The following general formula (5)
Is an organic group containing at least one fluorine atom. R 6 represents a hydrophilic organic group or an organic group bonded via a group containing a phosphorus atom or a group containing a sulfur atom. ) -Containing fluorinated lipid derivative.
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JP2009007460A (en) * | 2007-06-27 | 2009-01-15 | Nippon Polyurethane Ind Co Ltd | Organic polyisocyanate composition, and coating composition and adhesive composition using the same |
WO2012014818A1 (en) * | 2010-07-30 | 2012-02-02 | 日本ゼオン株式会社 | Ether compound, electrolyte composition for non-aqueous battery, binder composition for non-aqueous battery electrode, slurry composition for non-aqueous battery electrode, electrode for non-aqueous battery and non-aqueous battery |
JP2015172011A (en) * | 2014-03-11 | 2015-10-01 | 国立研究開発法人産業技術総合研究所 | Pseudo-cyclic lipid compound |
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JP2009007460A (en) * | 2007-06-27 | 2009-01-15 | Nippon Polyurethane Ind Co Ltd | Organic polyisocyanate composition, and coating composition and adhesive composition using the same |
WO2012014818A1 (en) * | 2010-07-30 | 2012-02-02 | 日本ゼオン株式会社 | Ether compound, electrolyte composition for non-aqueous battery, binder composition for non-aqueous battery electrode, slurry composition for non-aqueous battery electrode, electrode for non-aqueous battery and non-aqueous battery |
CN103038224A (en) * | 2010-07-30 | 2013-04-10 | 日本瑞翁株式会社 | Ether compound, electrolyte composition for non-aqueous battery, binder composition for non-aqueous battery electrode, slurry composition for non-aqueous battery electrode, electrode for non-aqueous battery and non-aqueous battery |
JPWO2012014818A1 (en) * | 2010-07-30 | 2013-09-12 | 日本ゼオン株式会社 | Ether compound, non-aqueous battery electrolyte composition, non-aqueous battery electrode binder composition, non-aqueous battery electrode slurry composition, non-aqueous battery electrode and non-aqueous battery |
JP2015172011A (en) * | 2014-03-11 | 2015-10-01 | 国立研究開発法人産業技術総合研究所 | Pseudo-cyclic lipid compound |
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