IL211795A - תהליך להכנת פוספוליפידים מחומצנים - Google Patents

Info

Publication number

IL211795A

IL211795A IL211795A IL21179511A IL211795A IL 211795 A IL211795 A IL 211795A IL 211795 A IL211795 A IL 211795A IL 21179511 A IL21179511 A IL 21179511A IL 211795 A IL211795 A IL 211795A

Authority

IL

Israel

Prior art keywords

compound

moiety

group

glycerolic backbone

oxidized

Prior art date

2004-07-09

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims description 126
• 150000003904 phospholipids Chemical class 0.000 title description 66
• 238000002360 preparation method Methods 0.000 title description 37
• 230000008569 process Effects 0.000 title description 35
• 150000001875 compounds Chemical class 0.000 claims description 442
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 109
• 239000000203 mixture Substances 0.000 claims description 69
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
• 239000011541 reaction mixture Substances 0.000 claims description 50
• -1 lithium aluminum hydride Chemical compound 0.000 claims description 45
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 33
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 32
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 30
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 30
• 125000004432 carbon atom Chemical group C* 0.000 claims description 29
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 150000002009 diols Chemical class 0.000 claims description 26
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 26
• SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical group NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 18
• 229910019142 PO4 Inorganic materials 0.000 claims description 14
• 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 14
• YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical group C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 14
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 13
• 235000011180 diphosphates Nutrition 0.000 claims description 13
• 239000010452 phosphate Substances 0.000 claims description 13
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 12
• 150000002148 esters Chemical class 0.000 claims description 12
• AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 12
• 239000011574 phosphorus Substances 0.000 claims description 12
• 229910052698 phosphorus Inorganic materials 0.000 claims description 12
• 229950004354 phosphorylcholine Drugs 0.000 claims description 12
• GIELSVRJHGSIJE-UHFFFAOYSA-N (oxo-lambda5-phosphanylidyne)methanol Chemical group P(=O)#CO GIELSVRJHGSIJE-UHFFFAOYSA-N 0.000 claims description 11
• OKLITDBMRKBZLC-UHFFFAOYSA-N 3-(oxo-$l^{5}-phosphanylidyne)propan-1-ol Chemical group OCCC#P=O OKLITDBMRKBZLC-UHFFFAOYSA-N 0.000 claims description 11
• VDRKXDRYHWOORA-UHFFFAOYSA-N 4-(oxo-$l^{5}-phosphanylidyne)butan-1-ol Chemical group OCCCC#P=O VDRKXDRYHWOORA-UHFFFAOYSA-N 0.000 claims description 11
• SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 11
• JGENYNHRIOHZOP-UHFFFAOYSA-N ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical group CCOP([O-])(=O)OCC[N+](C)(C)C JGENYNHRIOHZOP-UHFFFAOYSA-N 0.000 claims description 11
• 229960000367 inositol Drugs 0.000 claims description 11
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 11
• BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoserine Chemical group OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 claims description 10
• 150000004820 halides Chemical group 0.000 claims description 10
• 239000008101 lactose Substances 0.000 claims description 10
• QQHVEZXEGWKJEP-UHFFFAOYSA-N 2-(oxo-lambda5-phosphanylidyne)ethanol Chemical group OCC#P=O QQHVEZXEGWKJEP-UHFFFAOYSA-N 0.000 claims description 9
• VZYZHAVHYMUSNJ-UHFFFAOYSA-N [2-(dinitroamino)-1-phenylethyl] dihydrogen phosphate Chemical compound [N+](=O)([O-])N(CC(OP(=O)(O)O)C1=CC=CC=C1)[N+](=O)[O-] VZYZHAVHYMUSNJ-UHFFFAOYSA-N 0.000 claims description 9
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 9
• TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical group CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims description 8
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Chemical group NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 8
• ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Chemical group OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 8
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
• 150000008104 phosphatidylethanolamines Chemical group 0.000 claims description 8
• 150000003905 phosphatidylinositols Chemical group 0.000 claims description 8
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
• 150000001241 acetals Chemical class 0.000 claims description 7
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 5
• 150000001266 acyl halides Chemical class 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• 229910000104 sodium hydride Inorganic materials 0.000 claims description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
• 239000012312 sodium hydride Substances 0.000 claims description 3
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
• 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
• 239000002904 solvent Substances 0.000 description 97
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 91
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 83
• 239000000243 solution Substances 0.000 description 77
• PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 72
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 70
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
• 239000007800 oxidant agent Substances 0.000 description 44
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• 150000001299 aldehydes Chemical class 0.000 description 35
• 125000006239 protecting group Chemical group 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 28
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
• 239000012074 organic phase Substances 0.000 description 26
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 24
• 239000000047 product Substances 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 230000001590 oxidative effect Effects 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 20
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 18
• 238000001914 filtration Methods 0.000 description 18
• 238000007254 oxidation reaction Methods 0.000 description 18
• 150000002118 epoxides Chemical class 0.000 description 17
• 239000012535 impurity Substances 0.000 description 17
• 150000002632 lipids Chemical class 0.000 description 17
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 17
• 150000002313 glycerolipids Chemical class 0.000 description 16
• 230000003647 oxidation Effects 0.000 description 15
• 230000009286 beneficial effect Effects 0.000 description 13
• 229960004592 isopropanol Drugs 0.000 description 13
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• 150000002431 hydrogen Chemical group 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 125000002947 alkylene group Chemical group 0.000 description 10
• 150000002327 glycerophospholipids Chemical class 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• 150000002978 peroxides Chemical class 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 229910001919 chlorite Inorganic materials 0.000 description 8
• 229910052619 chlorite group Inorganic materials 0.000 description 8
• QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 8
• 238000001035 drying Methods 0.000 description 8
• 235000019439 ethyl acetate Nutrition 0.000 description 8
• 238000000605 extraction Methods 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 239000012071 phase Substances 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 238000000926 separation method Methods 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 201000001320 Atherosclerosis Diseases 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• 125000004103 aminoalkyl group Chemical group 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000006227 byproduct Substances 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical group [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
• 238000010533 azeotropic distillation Methods 0.000 description 5
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
• 125000000753 cycloalkyl group Chemical group 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 150000004665 fatty acids Chemical class 0.000 description 5
• 231100001261 hazardous Toxicity 0.000 description 5
• 239000002502 liposome Substances 0.000 description 5
• 238000007040 multi-step synthesis reaction Methods 0.000 description 5
• 108010071584 oxidized low density lipoprotein Proteins 0.000 description 5
• 125000005547 pivalate group Chemical group 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• 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 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 230000002051 biphasic effect Effects 0.000 description 4
• 150000001768 cations Chemical class 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 238000002955 isolation Methods 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 229910052751 metal Inorganic materials 0.000 description 4
• 239000002184 metal Substances 0.000 description 4
• 238000007248 oxidative elimination reaction Methods 0.000 description 4
• 239000003208 petroleum Substances 0.000 description 4
• 239000011591 potassium Substances 0.000 description 4
• 229910052700 potassium Inorganic materials 0.000 description 4
• 239000012286 potassium permanganate Substances 0.000 description 4
• NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• YSULOORXQBDPCU-UHFFFAOYSA-N 2-(trimethylazaniumyl)ethanehydrazonate;hydrochloride Chemical group [Cl-].C[N+](C)(C)CC(=O)NN YSULOORXQBDPCU-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 108010007622 LDL Lipoproteins Proteins 0.000 description 3
• 102000007330 LDL Lipoproteins Human genes 0.000 description 3
• 229910019213 POCl3 Inorganic materials 0.000 description 3
• SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 3
• XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
• 239000003814 drug Substances 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 239000012467 final product Substances 0.000 description 3
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
• 235000019799 monosodium phosphate Nutrition 0.000 description 3
• 239000012454 non-polar solvent Substances 0.000 description 3
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 238000001556 precipitation Methods 0.000 description 3
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
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• OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 2
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