DK168539B1 - Speciel fremgangsmåde til fremstilling af 26,26,26,27,27,27-hexafluor-1alfa,25-dihydroxycholesterol og mellemprodukter til brug herved - Google Patents

Speciel fremgangsmåde til fremstilling af 26,26,26,27,27,27-hexafluor-1alfa,25-dihydroxycholesterol og mellemprodukter til brug herved Download PDF

Info

Publication number: DK168539B1
Authority: DK; Denmark
Prior art keywords: formula; process according; hexafluoro; prepared; compound
Prior art date: 1982-05-26

Application number

DK032684A

Other languages

Danish (da)

English (en)

Other versions

DK32684D0 (da

DK32684A (da

Inventor

Hector F Deluca

Yoko Tanaka

Nobuo Ikekawa

Yoshiro Kobayashi

Original Assignee

Wisconsin Alumni Res Found

Priority date (The priority date 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 date listed.)

1982-05-26

Filing date

1984-01-25

Publication date

1994-04-18

1984-01-25 Application filed by Wisconsin Alumni Res Found filed Critical Wisconsin Alumni Res Found

1984-01-25 Publication of DK32684D0 publication Critical patent/DK32684D0/da

1984-01-25 Publication of DK32684A publication Critical patent/DK32684A/da

1994-04-18 Application granted granted Critical

1994-04-18 Publication of DK168539B1 publication Critical patent/DK168539B1/da

Links

238000000034 method Methods 0.000 title claims description 18
238000004519 manufacturing process Methods 0.000 title claims description 4
239000000543 intermediate Substances 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 18
150000002118 epoxides Chemical class 0.000 claims description 10
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 claims description 8
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 8
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 3
VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
150000004702 methyl esters Chemical class 0.000 claims description 3
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 claims description 2
229910001023 sodium amalgam Inorganic materials 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
238000006884 silylation reaction Methods 0.000 claims 2
GEUPGXRTDHHMLS-UHFFFAOYSA-N [Na]S(=O)(=O)C1=CC=CC=C1 Chemical compound [Na]S(=O)(=O)C1=CC=CC=C1 GEUPGXRTDHHMLS-UHFFFAOYSA-N 0.000 claims 1
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
230000010933 acylation Effects 0.000 claims 1
238000005917 acylation reaction Methods 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 claims 1
125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
230000031709 bromination Effects 0.000 claims 1
238000005893 bromination reaction Methods 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
150000002440 hydroxy compounds Chemical class 0.000 claims 1
230000003647 oxidation Effects 0.000 claims 1
238000007254 oxidation reaction Methods 0.000 claims 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
238000007363 ring formation reaction Methods 0.000 claims 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000011782 vitamin Substances 0.000 description 13
229940088594 vitamin Drugs 0.000 description 13
150000003722 vitamin derivatives Chemical class 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
229930003231 vitamin Natural products 0.000 description 12
235000013343 vitamin Nutrition 0.000 description 12
239000000203 mixture Substances 0.000 description 11
238000005481 NMR spectroscopy Methods 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000012267 brine Substances 0.000 description 7
239000011575 calcium Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
229910052791 calcium Inorganic materials 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000011734 sodium Substances 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
238000010828 elution Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000003054 hormonal effect Effects 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
150000003457 sulfones Chemical class 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 2
GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 2
GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
239000003872 25-hydroxy-cholecalciferol Substances 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
239000004380 Cholic acid Substances 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
229930003316 Vitamin D Natural products 0.000 description 2
QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
125000005103 alkyl silyl group Chemical group 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
239000011612 calcitriol Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 2
229960002471 cholic acid Drugs 0.000 description 2
235000019416 cholic acid Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000002904 solvent Substances 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
239000011710 vitamin D Substances 0.000 description 2
235000019166 vitamin D Nutrition 0.000 description 2
150000003710 vitamin D derivatives Chemical class 0.000 description 2
229940046008 vitamin d Drugs 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 1
FCKJYANJHNLEEP-OIMXRAFZSA-N 24,25-Dihydroxyvitamin D Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCC(O)C(C)(C)O)C)=C\C=C1\C[C@H](O)CCC1=C FCKJYANJHNLEEP-OIMXRAFZSA-N 0.000 description 1
JWUBBDSIWDLEOM-UHFFFAOYSA-N 25-Hydroxycholecalciferol Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CCC1=C JWUBBDSIWDLEOM-UHFFFAOYSA-N 0.000 description 1
235000021318 Calcifediol Nutrition 0.000 description 1
241000282421 Canidae Species 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
WTYCHAVEQAWVIZ-UHFFFAOYSA-N FC1C(C(C(C=C1)(F)S(=O)(=O)C1(C(C(C(C=C1)F)(F)F)(F)F)F)(F)F)(F)F Chemical compound FC1C(C(C(C=C1)(F)S(=O)(=O)C1(C(C(C(C=C1)F)(F)F)(F)F)F)(F)F)(F)F WTYCHAVEQAWVIZ-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
229960002535 alfacalcidol Drugs 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000001749 antrachitic effect Effects 0.000 description 1
TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 1
GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
230000003913 calcium metabolism Effects 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical compound C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
229960002061 ergocalciferol Drugs 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
150000002222 fluorine compounds Chemical class 0.000 description 1
125000001153 fluoro group Chemical class F* 0.000 description 1
239000007789 gas Substances 0.000 description 1
-1 hexafluoro compound Chemical class 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000031891 intestinal absorption Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000010907 mechanical stirring Methods 0.000 description 1
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
230000002969 morbid Effects 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
238000012958 reprocessing Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
238000005866 tritylation reaction Methods 0.000 description 1
239000011653 vitamin D2 Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton

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DK032684A 1982-05-26 1984-01-25 Speciel fremgangsmåde til fremstilling af 26,26,26,27,27,27-hexafluor-1alfa,25-dihydroxycholesterol og mellemprodukter til brug herved DK168539B1 (da)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US38205582		1982-05-26
US06/382,055 US4411833A (en)	1982-05-26	1982-05-26	Method for preparing 26,26,26,27,27,27-hexafluoro-1α,25-dihydroxycholesterol
PCT/US1983/000577 WO1983004256A1 (fr)	1982-05-26	1983-04-18	PROCEDE DE PREPARATION DE 26, 26, 26, 27, 27, 27-HEXAFLUORO-1alpha, 25-DIHYDROXYCHOLESTEROL
US8300577		1983-04-18

Publications (3)

Publication Number	Publication Date
DK32684D0 DK32684D0 (da)	1984-01-25
DK32684A DK32684A (da)	1984-01-25
DK168539B1 true DK168539B1 (da)	1994-04-18

Family

ID=23507359

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK032684A DK168539B1 (da)	1982-05-26	1984-01-25	Speciel fremgangsmåde til fremstilling af 26,26,26,27,27,27-hexafluor-1alfa,25-dihydroxycholesterol og mellemprodukter til brug herved

Country Status (14)

Country	Link
US (1)	US4411833A (fr)
JP (2)	JPH0742305B2 (fr)
AU (1)	AU561182B2 (fr)
BE (1)	BE896830A (fr)
CH (2)	CH663212A5 (fr)
DE (1)	DE3390016C2 (fr)
DK (1)	DK168539B1 (fr)
FR (2)	FR2527615B1 (fr)
GB (2)	GB2121044B (fr)
IE (1)	IE55022B1 (fr)
IL (1)	IL68537A (fr)
IT (1)	IT1203706B (fr)
NL (1)	NL8320153A (fr)
WO (1)	WO1983004256A1 (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4613594A (en) *	1984-11-16	1986-09-23	Hoffmann-La Roche Inc.	Fluorinated vitamin D3 compounds
US4749710A (en) *	1985-05-01	1988-06-07	Hoffmann-La Roche Inc.	Immunosuppressive agents
US4619920A (en) *	1985-09-16	1986-10-28	Wisconsin Alumni Research Foundation	26,26,26,27,27-pentafluoro-1α-hydroxy-27-methoxyvitamin D3
JPH0764804B2 (ja) *	1986-04-25	1995-07-12	住友製薬株式会社	活性型ビタミンｄ３のフッ素誘導体
WO1990009179A1 (fr) *	1989-02-16	1990-08-23	University Of Georgia Research Foundation, Inc.	Traitement de la dyschondroplasie tibiale d'allien
US5366736A (en) *	1989-02-16	1994-11-22	University Of Georgia Research Foundation, Inc.	Vitamin D derivative feed compositions and methods of use
US5316770A (en) *	1989-02-16	1994-05-31	University Of Georgia Research Foundation, Inc.	Vitamin D derivative feed compositions and methods of use
AU6247194A (en) *	1993-02-19	1994-09-14	Wisconsin Alumni Research Foundation	Use of 26,26,26,27,27,27-hexafluoro-1alpha,25-dihydroxycholecalcife rol for the treatment of calcium metabolism disorders
JP2009532458A (ja) *	2006-04-06	2009-09-10	ウイスコンシンアラムニリサーチファンデーション	２−メチレン−１α−ヒドロキシ−１９，２１−ジノルビタミンＤ３類縁体およびその使用
NZ570712A (en) *	2006-04-06	2011-11-25	Wisconsin Alumni Res Found	2-methylene-1alpha-hydroxy-18,19,21-trinorvitamin D3 analogs and uses thereof
AU2007291005A1 (en) *	2006-04-06	2008-03-06	Wisconsin Alumni Research Foundation	19-nor-vitamin D analogs with 1,2,or 3,2 heterocyclic ring
CA2639585A1 (fr) *	2006-04-06	2007-10-06	Wisconsin Alumni Research Foundation	2-methylene-1.alpha.-25-dihydroxy-18,19,21-trinor-vitamine d3 et utilisations connexes
US8404666B2 (en)	2006-04-06	2013-03-26	Wisconsin Alumni Research Foundation	2-substituted-1α,25-dihydroxy-19,26,27-trinor vitamin D analogs and uses thereof
MX2008012912A (es) *	2006-04-06	2008-11-26	Wisconsin Alumni Res Found	Analogos de 2-metilen-1a,25-dihidroxi-19,21-dinorvitamina d3 y sus usos.
NZ570816A (en) *	2006-04-10	2011-07-29	Wisconsin Alumni Res Found	1alpha-hydroxy-2-(3'-hydroxypropylidene)-19-nor-vitamin D compounds with a 1,1-dimethylpropyl side chain
AU2010208323B2 (en)	2009-01-27	2016-03-10	Berg Llc	Vitamin D3 and analogs thereof for alleviating side effects associated with chemotherapy
EP2464357B1 (fr)	2009-08-14	2019-05-22	Berg LLC	Vitamine d3 et ses analogues pour le traitement de l'alopécie
SG10201709894RA (en)	2013-05-29	2018-01-30	Berg Llc	Preventing or mitigating chemotherapy induced alopecia using vitamin d
CN113968888B (zh) *	2020-07-24	2023-06-27	上海医药工业研究院	一种胆甾衍生物的制备方法、其中间体及应用

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4183852A (en) *	1977-07-18	1980-01-15	Kaiser Emil T	Process for preparing 25-hydroxycholesterol
LU80545A1 (de) *	1978-11-17	1980-06-05	Hoffmann La Roche	Verfahren zur herstellung von 1a,3s-dihydroxy->5-steroiden
US4217279A (en) *	1978-12-18	1980-08-12	Kaiser Emil T	Synthesis of steroids
JPS5598199A (en) *	1979-01-17	1980-07-25	Eisai Co Ltd	Preparation of 25-hydroxy cholesta-1,4,6-trien-3-one
US4269777A (en) *	1979-05-21	1981-05-26	Wisconsin Alumni Research Foundation	Isotopically labeled vitamin D derivatives and processes for preparing same
IL60270A0 (en) *	1979-06-14	1980-09-16	Diamond Shamrock Corp	Preparation of 25-ydroxycholesterol
US4248791A (en) *	1980-02-04	1981-02-03	Wisconsin Alumni Research Foundation	25-Hydroxy-26,26,26,27,27,27-hexafluorocholecalciferol
US4360470A (en) *	1980-10-22	1982-11-23	Hoffmann-La Roche Inc.	Process and intermediates for the synthesis of Vitamin D3 metabolites and chenodeoxycholic acid
US4358406A (en) *	1981-07-27	1982-11-09	Wisconsin Alumni Research Foundation	26,26,26,27,27,27-Hexafluoro-1α,25-dihydroxycholecalciferol and process for preparing same

1982
- 1982-05-26 US US06/382,055 patent/US4411833A/en not_active Expired - Lifetime
1983
- 1983-04-18 WO PCT/US1983/000577 patent/WO1983004256A1/fr not_active Ceased
- 1983-04-18 CH CH341/84A patent/CH663212A5/de not_active IP Right Cessation
- 1983-04-18 AU AU15542/83A patent/AU561182B2/en not_active Ceased
- 1983-04-18 DE DE19833390016 patent/DE3390016C2/de not_active Expired
- 1983-04-18 CH CH4413/86A patent/CH662572A5/de not_active IP Right Cessation
- 1983-04-18 NL NL8320153A patent/NL8320153A/nl not_active Application Discontinuation
- 1983-04-29 IL IL68537A patent/IL68537A/xx not_active IP Right Cessation
- 1983-05-24 IT IT21261/83A patent/IT1203706B/it active
- 1983-05-24 IE IE1226/83A patent/IE55022B1/en not_active IP Right Cessation
- 1983-05-25 FR FR8308650A patent/FR2527615B1/fr not_active Expired
- 1983-05-25 BE BE0/210839A patent/BE896830A/fr not_active IP Right Cessation
- 1983-05-26 GB GB08314612A patent/GB2121044B/en not_active Expired
- 1983-11-04 FR FR8317598A patent/FR2533929B1/fr not_active Expired
1984
- 1984-01-25 DK DK032684A patent/DK168539B1/da active IP Right Grant
- 1984-06-19 GB GB08415630A patent/GB2140016B/en not_active Expired
1992
- 1992-01-23 JP JP4032644A patent/JPH0742305B2/ja not_active Expired - Lifetime
- 1992-01-23 JP JP4032645A patent/JPH0742306B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
IL68537A0 (en)	1983-07-31
GB2121044B (en)	1986-01-02
DK32684D0 (da)	1984-01-25
BE896830A (fr)	1983-09-16
DK32684A (da)	1984-01-25
GB2121044A (en)	1983-12-14
US4411833A (en)	1983-10-25
WO1983004256A1 (fr)	1983-12-08
FR2533929B1 (fr)	1986-10-31
FR2527615B1 (fr)	1986-05-23
IL68537A (en)	1986-07-31
IT1203706B (it)	1989-02-15
IE55022B1 (en)	1990-04-25
AU1554283A (en)	1983-12-16
NL8320153A (nl)	1984-04-02
JPH0742305B2 (ja)	1995-05-10
DE3390016C2 (de)	1989-08-10
IT8321261A0 (it)	1983-05-24
DE3390016T1 (de)	1984-05-17
AU561182B2 (en)	1987-04-30
JPH0742306B2 (ja)	1995-05-10
CH663212A5 (de)	1987-11-30
GB8314612D0 (en)	1983-06-29
GB2140016A (en)	1984-11-21
IE831226L (en)	1983-11-26
JPH0578388A (ja)	1993-03-30
CH662572A5 (de)	1987-10-15
GB8415630D0 (en)	1984-07-25
JPH0578387A (ja)	1993-03-30
FR2533929A1 (fr)	1984-04-06
GB2140016B (en)	1986-01-02
FR2527615A1 (fr)	1983-12-02

Legal Events

Date	Code	Title	Description
1994-04-18	B1	Patent granted (law 1993)

Publication	Publication Date	Title
US4411833A (en)	1983-10-25	Method for preparing 26,26,26,27,27,27-hexafluoro-1α,25-dihydroxycholesterol
DK170437B1 (da)	1995-09-04	1alfa-hydroxy-3,5-cyclovitamin D forbindelser
EP0078705B1 (fr)	1988-04-27	Procédé de préparation de dérivés de vitamine D 1-hydroxyles
IE54370B1 (en)	1989-09-13	26, 26, 26, 27, 27, 27-hexyfluoro-cholesterol derivatives
NL8420179A (nl)	1985-07-01	23,23-difluro- 1 alfa, 25 dihydroxy-vitamine d3.
US5089641A (en)	1992-02-18	Synthesis of 1α-hydroxy-secosterol compounds
DK147178B (da)	1984-05-07	Fremgangsmaade til 1-hydroxylering af 5,6-trans-vitamin d-forbindelser
US3846455A (en)	1974-11-05	Process for the preparation of 25-hydroxy-cholesterol and esters thereof
DK158990B (da)	1990-08-13	Cholestadienderivat, der kan anvendes som mellemprodukt til brug ved fremstillingen af homovitamin-d3-derivater
Morris et al.	1981	Structure and synthesis of 25-hydroxycholecalciferol-26, 23-lactone, a metabolite of vitamin D
GB1564806A (en)	1980-04-16	Cholesterol derivatives
US5182393A (en)	1993-01-26	Process for precursors to calcitriol and related compounds
EP0503923B1 (fr)	1994-12-28	Systhèse des dérivés de 1-alpha-hydroxy secosterol
EP0045524A1 (fr)	1982-02-10	22-Arylsulfonyl-24,25-dihydroxycholestanes et procédé pour les préparer
EP0528209B1 (fr)	1999-11-10	Procédé de préparation d'intermédiaires pour dérivées de la vitamine D et composés
EP0250755A2 (fr)	1988-01-07	Dérivés fluorés de la vitamine D3 et procédé de préparation
EP0157781A4 (fr)	1985-12-30	Composes de 1,23-dihydroxyvitamine d.
US5225569A (en)	1993-07-06	Process for precursors to calcitriol and related compounds
JP3483155B2 (ja)	2004-01-06	１α，２５−ジヒドロキシビタミンＤ４およびＤ７の製造法
JPS59500864A (ja)	1984-05-17	２６，２６．２６，２７．２７，２７―ヘキサフルオロ―１α，２５―ジヒドロキシコレステロール化合物及びその製造方法
JP2683395B2 (ja)	1997-11-26	ステロイド誘導体
JP2750170B2 (ja)	1998-05-13	ステロイド誘導体の製造法
Schrötter et al.	1988	An improved synthesis of (24R)‐3β‐(2H‐Tetrahydropyran‐2‐yloxy) cholesta‐5, 7‐diene‐24, 25‐diol–a key intermediate in the synthesis of (24R)‐24, 25‐dihydroxyvitamin D3
JPS63264452A (ja)	1988-11-01	フッ素化ビタミンｄ↓３誘導体
KONDO et al.	1996	The first synthesis of 24, 24-difluoro-1α-hydroxyvitamin D3 by means of radical deoxygenation of alcohols