DK172151B1 - Fremgangsmåde til fremstilling af 1alfa-hydroxyvitamin-D- eller 1alfa-hydroxy-previtamin-D-forbindelser og addukt af en previtamin-D- eller tachysterolforbindelse med et dienophil - Google Patents

Fremgangsmåde til fremstilling af 1alfa-hydroxyvitamin-D- eller 1alfa-hydroxy-previtamin-D-forbindelser og addukt af en previtamin-D- eller tachysterolforbindelse med et dienophil Download PDF

Info

Publication number: DK172151B1
Authority: DK; Denmark
Prior art keywords: previtamin; compound; hydroxy; reaction; adduct
Prior art date: 1981-07-17

Application number

DK315782A

Other languages

Danish (da)

English (en)

Other versions

DK315782A (da

Inventor

Maurits Vandewalle

Luc J Vanmaele

Pierre J De Clercq

Sebastianus J Halkes

Wilhelmus R M Overbeek

Original Assignee

Duphar Int Res

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.)

1981-07-17

Filing date

1982-07-14

Publication date

1997-12-01

1982-07-14 Application filed by Duphar Int Res filed Critical Duphar Int Res

1983-01-18 Publication of DK315782A publication Critical patent/DK315782A/da

1997-12-01 Application granted granted Critical

1997-12-01 Publication of DK172151B1 publication Critical patent/DK172151B1/da

Links

-1 tachysterol compound Chemical class 0.000 title claims abstract description 94
238000000034 method Methods 0.000 title claims abstract description 32
YUGCAAVRZWBXEQ-WHTXLNIXSA-N previtamin D3 Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)CCCC(C)C)\C=C/C1=C(C)CC[C@H](O)C1 YUGCAAVRZWBXEQ-WHTXLNIXSA-N 0.000 title claims abstract description 30
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 title claims abstract description 17
BUNBVCKYYMRTNS-UHFFFAOYSA-N tachysterol Natural products C=1CCC2(C)C(C(C)CCC(C)C(C)C)CCC2C=1C=CC1=C(C)CCC(O)C1 BUNBVCKYYMRTNS-UHFFFAOYSA-N 0.000 title claims abstract description 15
238000002360 preparation method Methods 0.000 title claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 27
125000006239 protecting group Chemical group 0.000 claims abstract description 10
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims abstract description 5
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims abstract description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 42
238000006243 chemical reaction Methods 0.000 claims description 39
150000001875 compounds Chemical class 0.000 claims description 27
238000007254 oxidation reaction Methods 0.000 claims description 24
239000000047 product Substances 0.000 claims description 23
239000003795 chemical substances by application Substances 0.000 claims description 21
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 claims description 19
230000003647 oxidation Effects 0.000 claims description 17
239000011710 vitamin D Substances 0.000 claims description 17
229940046008 vitamin d Drugs 0.000 claims description 17
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
229930003316 Vitamin D Natural products 0.000 claims description 15
239000007800 oxidant agent Substances 0.000 claims description 15
235000019166 vitamin D Nutrition 0.000 claims description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 14
229910052987 metal hydride Inorganic materials 0.000 claims description 14
ISULLEUFOQSBGY-UHFFFAOYSA-N 4-phenyl-1,2,4-triazole-3,5-dione Chemical compound O=C1N=NC(=O)N1C1=CC=CC=C1 ISULLEUFOQSBGY-UHFFFAOYSA-N 0.000 claims description 13
239000007858 starting material Substances 0.000 claims description 13
230000007062 hydrolysis Effects 0.000 claims description 12
238000006460 hydrolysis reaction Methods 0.000 claims description 12
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 12
YSZIOXAEADAJLX-UHFFFAOYSA-N phthalazine-1,4-dione Chemical compound C1=CC=C2C(=O)N=NC(=O)C2=C1 YSZIOXAEADAJLX-UHFFFAOYSA-N 0.000 claims description 12
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 11
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 11
229910052804 chromium Inorganic materials 0.000 claims description 11
239000011651 chromium Substances 0.000 claims description 11
239000003960 organic solvent Substances 0.000 claims description 10
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
238000005886 esterification reaction Methods 0.000 claims description 8
BNSOYWDFFBDEFB-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O BNSOYWDFFBDEFB-UHFFFAOYSA-L 0.000 claims description 8
239000012280 lithium aluminium hydride Substances 0.000 claims description 8
150000004681 metal hydrides Chemical class 0.000 claims description 8
230000001590 oxidative effect Effects 0.000 claims description 8
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims description 8
239000007795 chemical reaction product Substances 0.000 claims description 7
YUGCAAVRZWBXEQ-UHFFFAOYSA-N Precholecalciferol Natural products C=1CCC2(C)C(C(C)CCCC(C)C)CCC2C=1C=CC1=C(C)CCC(O)C1 YUGCAAVRZWBXEQ-UHFFFAOYSA-N 0.000 claims description 6
230000032050 esterification Effects 0.000 claims description 6
MARXMDRWROUXMD-UHFFFAOYSA-N 2-bromoisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Br)C(=O)C2=C1 MARXMDRWROUXMD-UHFFFAOYSA-N 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 5
150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 5
238000006266 etherification reaction Methods 0.000 claims description 5
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 5
238000005805 hydroxylation reaction Methods 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
229940088594 vitamin Drugs 0.000 claims description 5
239000011782 vitamin Substances 0.000 claims description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 4
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 4
AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 4
MMKQSIQNDMIVIN-UHFFFAOYSA-N oxido-(oxido(dioxo)chromio)oxy-dioxochromium;tetrabutylazanium Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC MMKQSIQNDMIVIN-UHFFFAOYSA-N 0.000 claims description 4
230000000707 stereoselective effect Effects 0.000 claims description 4
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
239000003638 chemical reducing agent Substances 0.000 claims description 3
238000002955 isolation Methods 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
150000003710 vitamin D derivatives Chemical class 0.000 claims description 3
BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 claims description 2
BCEIUDAMUFAQMG-UHFFFAOYSA-M CC(C)(C)O[Cr](O)(=O)=O Chemical compound CC(C)(C)O[Cr](O)(=O)=O BCEIUDAMUFAQMG-UHFFFAOYSA-M 0.000 claims description 2
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
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 claims description 2
VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 claims description 2
NCBFTYFOPLPRBX-UHFFFAOYSA-N dimethyl azodicarboxylate Substances COC(=O)N=NC(=O)OC NCBFTYFOPLPRBX-UHFFFAOYSA-N 0.000 claims description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
150000002222 fluorine compounds Chemical class 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
229940098779 methanesulfonic acid Drugs 0.000 claims description 2
229910052709 silver Inorganic materials 0.000 claims description 2
239000004332 silver Substances 0.000 claims description 2
125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 1
VMWZRHGIAVCFNS-UHFFFAOYSA-J aluminum;lithium;tetrahydroxide Chemical compound [Li+].[OH-].[OH-].[OH-].[OH-].[Al+3] VMWZRHGIAVCFNS-UHFFFAOYSA-J 0.000 claims 1
RAUONJSLIRWLFU-UHFFFAOYSA-N chromium(6+) 3,5-dimethyl-1H-pyrazole oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6].CC=1C=C(C)NN=1 RAUONJSLIRWLFU-UHFFFAOYSA-N 0.000 claims 1
150000004696 coordination complex Chemical class 0.000 claims 1
229910052500 inorganic mineral Inorganic materials 0.000 claims 1
230000002452 interceptive effect Effects 0.000 claims 1
239000011707 mineral Substances 0.000 claims 1
230000000640 hydroxylating effect Effects 0.000 abstract description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 139
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 94
239000000243 solution Substances 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
239000003480 eluent Substances 0.000 description 21
239000002904 solvent Substances 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 15
238000004440 column chromatography Methods 0.000 description 14
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 14
238000003756 stirring Methods 0.000 description 14
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
238000009835 boiling Methods 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
150000002009 diols Chemical class 0.000 description 7
238000001035 drying Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 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)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 7
XQFJZHAVTPYDIQ-LETJEVNCSA-N (1s)-3-[(e)-2-[(1r,3ar,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)/C=C/[C@H](C)C(C)C)\C=C\C1=C(C)CC[C@H](O)C1 XQFJZHAVTPYDIQ-LETJEVNCSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
239000010410 layer Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 5
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 5
238000005893 bromination reaction Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
238000000746 purification Methods 0.000 description 5
238000009281 ultraviolet germicidal irradiation Methods 0.000 description 5
MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 5
UCTLRSWJYQTBFZ-UHFFFAOYSA-N Dehydrocholesterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CC=C21 UCTLRSWJYQTBFZ-UHFFFAOYSA-N 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
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
229930003231 vitamin Natural products 0.000 description 4
235000013343 vitamin Nutrition 0.000 description 4
239000011647 vitamin D3 Substances 0.000 description 4
235000005282 vitamin D3 Nutrition 0.000 description 4
229940021056 vitamin d3 Drugs 0.000 description 4
150000003722 vitamin derivatives Chemical class 0.000 description 4
XQFJZHAVTPYDIQ-BIADAZNZSA-N (1s)-3-[(z)-2-[(1r,3ar,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)/C=C/[C@H](C)C(C)C)\C=C/C1=C(C)CC[C@H](O)C1 XQFJZHAVTPYDIQ-BIADAZNZSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 3
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
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125000000746 allylic group Chemical group 0.000 description 3
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 3
238000001914 filtration Methods 0.000 description 3
230000033444 hydroxylation Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
230000007017 scission Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 3
ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
238000000862 absorption spectrum Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000031709 bromination Effects 0.000 description 2
244000309464 bull Species 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
JJFYNCJHSCTBPW-TVQCKQBJSA-N cholesta-5,7-dien-3beta,25-diol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H](CCCC(C)(C)O)C)CC[C@H]33)C)C3=CC=C21 JJFYNCJHSCTBPW-TVQCKQBJSA-N 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000002178 crystalline material Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000012467 final product Substances 0.000 description 2
UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000011084 recovery Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
229910001958 silver carbonate Inorganic materials 0.000 description 2
238000005406 washing Methods 0.000 description 2
IICQXOJPUDICND-UHFFFAOYSA-N 1,2,4-triazole-3,5-dione Chemical group O=C1NC(=O)N=N1 IICQXOJPUDICND-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 1
SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
GOSUFRDROXZXLN-UHFFFAOYSA-N 4-phenyl-1,2,4-triazolidine-3,5-dione Chemical compound O=C1NNC(=O)N1C1=CC=CC=C1 GOSUFRDROXZXLN-UHFFFAOYSA-N 0.000 description 1
RIQIOKOQHGSKLN-UHFFFAOYSA-N 5,5-dibromo-1,3-dimethylimidazolidine-2,4-dione Chemical compound CN1C(=O)N(C)C(Br)(Br)C1=O RIQIOKOQHGSKLN-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
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 1
229930194542 Keto Natural products 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
QUUDUVNKJWQDFG-BXWGOXEHSA-N Vitamin D3 butyrate Chemical compound C1[C@@H](OC(=O)CCC)CCC(=C)\C1=C/C=C\1[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CCC/1 QUUDUVNKJWQDFG-BXWGOXEHSA-N 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
OBIYOJRAUSKYFA-UHFFFAOYSA-N [O-2].[O-2].[O-2].[Cr+6].CC1=CNN=C1C Chemical compound [O-2].[O-2].[O-2].[Cr+6].CC1=CNN=C1C OBIYOJRAUSKYFA-UHFFFAOYSA-N 0.000 description 1
RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
PNZVFASWDSMJER-UHFFFAOYSA-N acetic acid;lead Chemical compound [Pb].CC(O)=O PNZVFASWDSMJER-UHFFFAOYSA-N 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
239000002585 base Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical compound CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 description 1
229960005084 calcitriol Drugs 0.000 description 1
230000003913 calcium metabolism Effects 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
HKXBNHCUPKIYDM-CGMHZMFXSA-N doxercalciferol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C HKXBNHCUPKIYDM-CGMHZMFXSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
239000012374 esterification agent Substances 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000000155 melt Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 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
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000005086 pumping Methods 0.000 description 1
238000007348 radical reaction Methods 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003511 tertiary amides Chemical class 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
230000005945 translocation Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- 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
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Obesity (AREA)
Life Sciences & Earth Sciences (AREA)
Hematology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Diabetes (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Nutrition Science (AREA)
Endocrinology (AREA)
Rheumatology (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

DK315782A 1981-07-17 1982-07-14 Fremgangsmåde til fremstilling af 1alfa-hydroxyvitamin-D- eller 1alfa-hydroxy-previtamin-D-forbindelser og addukt af en previtamin-D- eller tachysterolforbindelse med et dienophil DK172151B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
NL8103393		1981-07-17
NL8103393		1981-07-17

Publications (2)

Publication Number	Publication Date
DK315782A DK315782A (da)	1983-01-18
DK172151B1 true DK172151B1 (da)	1997-12-01

Family

ID=19837798

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK315782A DK172151B1 (da)	1981-07-17	1982-07-14	Fremgangsmåde til fremstilling af 1alfa-hydroxyvitamin-D- eller 1alfa-hydroxy-previtamin-D-forbindelser og addukt af en previtamin-D- eller tachysterolforbindelse med et dienophil

Country Status (9)

Country	Link
US (1)	US4539153A (es)
EP (1)	EP0070588B1 (es)
JP (3)	JPS5823660A (es)
AT (1)	ATE19623T1 (es)
CA (1)	CA1327977C (es)
DE (1)	DE3270978D1 (es)
DK (1)	DK172151B1 (es)
ES (1)	ES8308847A1 (es)
IL (1)	IL66317A (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2062299T3 (es) *	1989-06-15	1994-12-16	Duphar Int Res	Aldehido aducto y su uso para la preparacion de un compuesto de vitamina d.
CH681152A5 (de) *	1991-06-04	1993-01-29	Marigen S.A.	Neue biotenside und antitumorale ester und phosphatide mit vitamin-d- und vitamin-e-verbindungen, ihre herstellung und aufarbeitung zu spontan dispergierbaren konzentraten.
ES2170069T3 (es) *	1992-06-22	2002-08-01	Bone Care Int Inc	1-alfa-hidroxiprevitamina d para administracion oral.
US5795882A (en) *	1992-06-22	1998-08-18	Bone Care International, Inc.	Method of treating prostatic diseases using delayed and/or sustained release vitamin D formulations
IN188477B (es) *	1998-06-23	2002-09-28	Hoffmann La Roche
EP1497264A2 (en) *	2002-04-11	2005-01-19	Instytut Farmaceutyczny	Preparation of 24-alkyl analogs of cholecalciferol and non-racemic compounds
US7253293B2 (en) *	2004-01-06	2007-08-07	Andrzej Slominski	Enzymatic method to produce 7-dehydropregnenolone, vitamin D3-like compounds and derivatives thereof
TW200714580A (en) *	2005-10-14	2007-04-16	Formosa Lab Inc	Process for preparing vitamin D analogs

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3901928A (en) *	1973-01-10	1975-08-26	Robert Henry Hesse	1' ,3' -dihydroxy steroid-5-enes method of preparing same and their use for preparing 1' -hydroxy-25-hydrogen vitamin d compounds
US3993675A (en) *	1975-02-24	1976-11-23	Hoffmann-La Roche Inc.	Process for the preparation of 1α,25-dihydroxycholecalciferol
US4069321A (en) *	1975-10-14	1978-01-17	Merck & Co., Inc.	Blocked cholecalciferol and dihydrotachysterol 3 derivatives
US4022768A (en) *	1976-02-12	1977-05-10	Wisconsin Alumni Research Foundation	Process for preparation of 1α,25-dihydroxycholecalciferol
US4110446A (en) *	1977-07-14	1978-08-29	Wisconsin Alumni Research Foundation	Method of treating milk fever in dairy cattle with 1,25-dihydroxycholecalciferol
US4202829A (en) *	1978-01-05	1980-05-13	Wisconsin Alumni Research Foundation	Process for preparing 1α-hydroxylated compounds
US4195027A (en) *	1978-01-16	1980-03-25	Wisconsin Alumni Research Foundation	Process for preparing 1α-hydroxylated compounds
US4206131A (en) *	1978-06-19	1980-06-03	The Upjohn Company	Compounds and process
JPS557215A (en) *	1978-06-30	1980-01-19	Teijin Ltd	Preparation of active vitamin d3 or its oh-protected derivative and/or its corresponding previtamin d3 or its oh-protected derivative
PH16989A (en) *	1978-11-07	1984-05-04	Res Inst Medicine Chem	Process for the preparation of 1-hydroxylated vitamin d compounds
US4335120A (en) *	1979-03-21	1982-06-15	Hoffmann-La Roche Inc.	Administration of biologically active vitamin D3 and vitamin D2 materials

1982
- 1982-07-05 DE DE8282200833T patent/DE3270978D1/de not_active Expired
- 1982-07-05 EP EP82200833A patent/EP0070588B1/en not_active Expired
- 1982-07-05 AT AT82200833T patent/ATE19623T1/de not_active IP Right Cessation
- 1982-07-14 ES ES513950A patent/ES8308847A1/es not_active Expired
- 1982-07-14 IL IL66317A patent/IL66317A/xx not_active IP Right Cessation
- 1982-07-14 DK DK315782A patent/DK172151B1/da not_active IP Right Cessation
- 1982-07-16 CA CA000407425A patent/CA1327977C/en not_active Expired - Fee Related
- 1982-07-16 JP JP57123065A patent/JPS5823660A/ja active Granted
1984
- 1984-07-31 US US06/636,782 patent/US4539153A/en not_active Expired - Lifetime
1987
- 1987-09-30 JP JP62244420A patent/JPS63107964A/ja active Granted
- 1987-09-30 JP JP62244419A patent/JPS6399053A/ja active Granted

Also Published As

Publication number	Publication date
EP0070588B1 (en)	1986-05-07
IL66317A0 (en)	1982-11-30
DK315782A (da)	1983-01-18
ATE19623T1 (de)	1986-05-15
JPS5823660A (ja)	1983-02-12
DE3270978D1 (en)	1986-06-12
CA1327977C (en)	1994-03-22
JPS63107964A (ja)	1988-05-12
JPS6399053A (ja)	1988-04-30
JPH0339058B2 (es)	1991-06-12
EP0070588A1 (en)	1983-01-26
IL66317A (en)	1987-07-31
JPH037664B2 (es)	1991-02-04
JPH0420431B2 (es)	1992-04-02
ES513950A0 (es)	1983-10-01
ES8308847A1 (es)	1983-10-01
US4539153A (en)	1985-09-03

Legal Events

Date	Code	Title	Description
1997-12-01	B1	Patent granted (law 1993)
2002-03-04	PBP	Patent lapsed

Publication	Publication Date	Title
EP0619304B1 (en)	1997-09-10	22-oxacholecalciferol derivative and production thereof
KR830000454B1 (ko)	1983-03-08	1-하이드록시-비타민 d 화합물의 제조방법
DK172151B1 (da)	1997-12-01	Fremgangsmåde til fremstilling af 1alfa-hydroxyvitamin-D- eller 1alfa-hydroxy-previtamin-D-forbindelser og addukt af en previtamin-D- eller tachysterolforbindelse med et dienophil
GB2108506A (en)	1983-05-18	Process for the preparation of 1-hydroxylated vitamin d compounds
Just et al.	1977	C-Nucleosides and related compounds. XIII. Synthesis of d, l-2′-deoxyshowdomycin (1 d)
US4758383A (en)	1988-07-19	Ergosta-1,5,7,22-tetraen-3β-ol and its use as an intermediate for 1α-hydroxy vitamin D2
US3929770A (en)	1975-12-30	Process for preparation of steroid derivative
US4022768A (en)	1977-05-10	Process for preparation of 1α,25-dihydroxycholecalciferol
SK281081B6 (sk)	2000-11-07	Spôsob výroby derivátov vitamínu d a aldehyd použiteľný ako medziprodukt
EP0045524B1 (en)	1983-10-19	22-arylsulfonyl-24,25-dihydroxycholestanes and process for preparing the same
US6040461A (en)	2000-03-21	Synthesis of 3-epi vitamin D3 metabolites and analogs
Tachibana	1988	A convenient synthesis of 1. ALPHA.-hydroxyvitamin D2.
US5087709A (en)	1992-02-11	Process for the preparation of 1α,25-dihydroxyvitamin D2 and the 24-epimer thereof
US4264510A (en)	1981-04-28	Intermediates in the production of anthracycline antibiotics
US4298537A (en)	1981-11-03	Process for producing steroid compounds having an oxo group in the side chain
JP3588367B2 (ja)	2004-11-10	１β−ヒドロキシ−１α−低級アルキルビタミンＤ誘導体
CA1127147A (en)	1982-07-06	STEROIDAL [16.alpha.,17-.beta.]BENZODIOXINS
NO300323B1 (no)	1997-05-12	Fremgangsmåte for fremstilling av astaxanthin, samt astaxanthindihemiaminaler og preparater som inneholder et slikt
Saitz et al.	1992	A facile synthesis of the pyranonaphthazarin system
JP2953665B2 (ja)	1999-09-27	ステロイド誘導体の製造方法
CA1055015A (en)	1979-05-22	Processes for preparation of steroid derivatives
JPH05339230A (ja)	1993-12-21	活性型ビタミンｄ２及びその誘導体の製造法
FR2477146A1 (fr)	1981-09-04	Procede pour la preparation d'acide calcitroique et de ses esters, et composes ainsi obtenus
WO2006052066A1 (en)	2006-05-18	Process for preparing 1-alpha-hydroxycholecalciferol derivatives
JPH04300865A (ja)	1992-10-23	活性型ビタミンｄ３誘導体の製造法