JPS6013735A - ６―デオキシアントラサイクリノン類の製法 - Google Patents
６―デオキシアントラサイクリノン類の製法Info
- Publication number
- JPS6013735A JPS6013735A JP59126567A JP12656784A JPS6013735A JP S6013735 A JPS6013735 A JP S6013735A JP 59126567 A JP59126567 A JP 59126567A JP 12656784 A JP12656784 A JP 12656784A JP S6013735 A JPS6013735 A JP S6013735A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- group
- treatment
- demethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 8
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 229930182470 glycoside Natural products 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 5
- 150000002338 glycosides Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 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 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 230000031709 bromination Effects 0.000 claims description 3
- 238000005893 bromination reaction Methods 0.000 claims description 3
- CRGRWBQSZSQVIE-UHFFFAOYSA-N diazomethylbenzene Chemical compound [N-]=[N+]=CC1=CC=CC=C1 CRGRWBQSZSQVIE-UHFFFAOYSA-N 0.000 claims description 3
- 125000000468 ketone group Chemical group 0.000 claims description 3
- 239000012286 potassium permanganate Substances 0.000 claims description 3
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 3
- 229940071536 silver acetate Drugs 0.000 claims description 3
- 150000008135 α-glycosides Chemical class 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- -1 Trifluoromethane sulfone Chemical class 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 238000010306 acid treatment Methods 0.000 claims 2
- 235000001674 Agaricus brunnescens Nutrition 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- YFKBXYGUSOXJGS-UHFFFAOYSA-N 1,3-Diphenyl-2-propanone Chemical compound C=1C=CC=CC=1CC(=O)CC1=CC=CC=C1 YFKBXYGUSOXJGS-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 5
- 229940045799 anthracyclines and related substance Drugs 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- QRIKXXKNWRKJDQ-UHFFFAOYSA-N 3-acetyl-6-methoxycarbonylcyclohex-3-ene-1-carboxylic acid Chemical compound COC(=O)C1CC=C(C(C)=O)CC1C(O)=O QRIKXXKNWRKJDQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 2
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 150000002596 lactones Chemical group 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007858 starting material 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
- 238000005406 washing Methods 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical class C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VVKMHTWFAUCCOD-UHFFFAOYSA-N 1-(3-aminopropyl)-8-[3-[2-(dimethylamino)-2-oxoethyl]anilino]-n-[(2-methylpyridin-4-yl)methyl]-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide Chemical group CN(C)C(=O)CC1=CC=CC(NC=2N=C3C=4N(CCCN)N=C(C=4CCC3=CN=2)C(=O)NCC=2C=C(C)N=CC=2)=C1 VVKMHTWFAUCCOD-UHFFFAOYSA-N 0.000 description 1
- MVAUFAJEEOAALP-UHFFFAOYSA-N 12h-tetracen-5-one Chemical compound C1=CC=C2C=C3C(=O)C4=CC=CC=C4CC3=CC2=C1 MVAUFAJEEOAALP-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical class O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101100083204 Microchaete diplosiphon cpcA3 gene Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy 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
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000006389 diacetylation reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LBUMBAFCSWSLPC-UHFFFAOYSA-N dimethyl 4-ethylidenecyclohexane-1,2-dicarboxylate Chemical compound COC(=O)C1CCC(=CC)CC1C(=O)OC LBUMBAFCSWSLPC-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- RMBWVUUBBVJUMH-UHFFFAOYSA-N methyl 5-(2-methyl-1,3-dioxolan-2-yl)-7-oxo-6-oxabicyclo[3.2.1]octane-2-carboxylate Chemical compound C1C(C(=O)O2)C(C(=O)OC)CCC21C1(C)OCCO1 RMBWVUUBBVJUMH-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 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
- 239000002966 varnish Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8317037 | 1983-06-23 | ||
| GB838317037A GB8317037D0 (en) | 1983-06-23 | 1983-06-23 | 6-deoxyanthracyclines |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4220019A Division JPH0735392B2 (ja) | 1983-06-23 | 1992-08-19 | アントラサイクリングリコシド類およびその製法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6013735A true JPS6013735A (ja) | 1985-01-24 |
| JPH058179B2 JPH058179B2 (h) | 1993-02-01 |
Family
ID=10544662
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59126567A Granted JPS6013735A (ja) | 1983-06-23 | 1984-06-21 | ６―デオキシアントラサイクリノン類の製法 |
| JP4220019A Expired - Lifetime JPH0735392B2 (ja) | 1983-06-23 | 1992-08-19 | アントラサイクリングリコシド類およびその製法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4220019A Expired - Lifetime JPH0735392B2 (ja) | 1983-06-23 | 1992-08-19 | アントラサイクリングリコシド類およびその製法 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US4939282A (h) |
| JP (2) | JPS6013735A (h) |
| AT (1) | AT390252B (h) |
| AU (2) | AU561456B2 (h) |
| BE (1) | BE899963A (h) |
| CA (1) | CA1234104A (h) |
| CH (2) | CH661922A5 (h) |
| CS (2) | CS243500B2 (h) |
| DK (2) | DK306484A (h) |
| FI (1) | FI842505A7 (h) |
| FR (1) | FR2549046B1 (h) |
| GB (1) | GB8317037D0 (h) |
| GR (1) | GR82130B (h) |
| HU (2) | HU196821B (h) |
| IL (1) | IL72168A (h) |
| IT (1) | IT1212101B (h) |
| NL (1) | NL8401957A (h) |
| SE (2) | SE8403353L (h) |
| SU (2) | SU1561821A3 (h) |
| ZA (1) | ZA844719B (h) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8197729B2 (en) | 2007-10-30 | 2012-06-12 | Toyo Engineering Corporation | Method of granulation with a fluidized bed granulator |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8317037D0 (en) * | 1983-06-23 | 1983-07-27 | Erba Farmitalia | 6-deoxyanthracyclines |
| GB2182926B (en) * | 1985-11-19 | 1989-10-04 | Erba Farmitalia | Nitro anthracyclines, process for their preparation and use thereof |
| GB8803301D0 (en) * | 1988-02-12 | 1988-03-09 | Erba Carlo Spa | Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin |
| IT1275953B1 (it) * | 1995-03-22 | 1997-10-24 | Sicor Spa | Procedimento per la preparazione di antibiotici della classe delle antracicline |
| US5948896A (en) * | 1997-08-13 | 1999-09-07 | Gem Pharmaceuticals | Processes for preparing 13-deoxy anthracycline derivatives |
| US5942605A (en) * | 1998-03-03 | 1999-08-24 | Gem Pharmaceuticals, Inc. | 5-imino-13-deoxy anthracycline derivatives, their uses, and processes for preparing them |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3803124A (en) * | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| GB1467383A (en) * | 1974-06-12 | 1977-03-16 | Farmaceutici Italia | Daunomycin analogues |
| GB1509875A (en) * | 1976-06-14 | 1978-05-04 | Farmaceutici Italia | Optically active anthracyclinones and anthracycline glycosides |
| GB1567456A (en) * | 1976-11-16 | 1980-05-14 | Farmaceutici Italia | Daunomycin derivatives |
| GB1573037A (en) * | 1977-05-05 | 1980-08-13 | Farmaceutici Italia | Anthracyclines |
| GB1573036A (en) * | 1977-05-05 | 1980-08-13 | Farmaceutici Italia | Anthracyclines |
| GB1567457A (en) * | 1977-11-11 | 1980-05-14 | Farmaceutici Italia | Daunomycinone derivatives |
| US4370476A (en) * | 1979-07-17 | 1983-01-25 | Usher Thomas C | Dextran polycarboxylic acids, ferric hydroxide complexes |
| US4348388A (en) * | 1980-04-02 | 1982-09-07 | G.D. Searle & Co. | 11-Amino-11-deoxydaunorubicin and analogs |
| US4374979A (en) * | 1981-04-27 | 1983-02-22 | The University Of Kansas Endowment Association | Regiospecific synthesis of anthracyclinone compounds such as daunomycinone |
| GB8317037D0 (en) * | 1983-06-23 | 1983-07-27 | Erba Farmitalia | 6-deoxyanthracyclines |
| IT1210476B (it) * | 1981-05-28 | 1989-09-14 | Erba Farmitalia | Antracicline. |
| DE3361316D1 (en) * | 1982-03-02 | 1986-01-09 | Sumitomo Chemical Co | Preparation of optically active 4-demethoxydaunomycinone |
| BE896743A (fr) * | 1982-08-13 | 1983-09-16 | Erba Farmitalia | Synthese de naphtacenequinone. |
-
1983
- 1983-06-23 GB GB838317037A patent/GB8317037D0/en active Pending
-
1984
- 1984-06-19 AU AU29524/84A patent/AU561456B2/en not_active Ceased
- 1984-06-19 US US06/622,177 patent/US4939282A/en not_active Expired - Fee Related
- 1984-06-19 AT AT0199684A patent/AT390252B/de not_active IP Right Cessation
- 1984-06-20 FR FR8409680A patent/FR2549046B1/fr not_active Expired
- 1984-06-20 FI FI842505A patent/FI842505A7/fi not_active Application Discontinuation
- 1984-06-20 IL IL72168A patent/IL72168A/xx unknown
- 1984-06-20 BE BE0/213174A patent/BE899963A/fr not_active IP Right Cessation
- 1984-06-20 NL NL8401957A patent/NL8401957A/xx not_active Application Discontinuation
- 1984-06-20 GR GR75063A patent/GR82130B/el unknown
- 1984-06-21 JP JP59126567A patent/JPS6013735A/ja active Granted
- 1984-06-21 CH CH3007/84A patent/CH661922A5/it not_active IP Right Cessation
- 1984-06-21 CS CS841254A patent/CS243500B2/cs unknown
- 1984-06-21 CH CH3510/86A patent/CH665422A5/it not_active IP Right Cessation
- 1984-06-21 SU SU843753950A patent/SU1561821A3/ru active
- 1984-06-21 ZA ZA844719A patent/ZA844719B/xx unknown
- 1984-06-21 SE SE8403353A patent/SE8403353L/xx not_active Application Discontinuation
- 1984-06-21 IT IT8421522A patent/IT1212101B/it active
- 1984-06-21 CS CS844740A patent/CS243490B2/cs unknown
- 1984-06-22 DK DK306484A patent/DK306484A/da not_active Application Discontinuation
- 1984-06-22 HU HU843650A patent/HU196821B/hu not_active IP Right Cessation
- 1984-06-22 CA CA000457254A patent/CA1234104A/en not_active Expired
- 1984-06-22 HU HU842436A patent/HU194902B/hu not_active IP Right Cessation
- 1984-12-13 SU SU843823254A patent/SU1429935A3/ru active
-
1987
- 1987-02-11 AU AU68818/87A patent/AU574599B2/en not_active Ceased
-
1989
- 1989-05-02 SE SE8901572A patent/SE8901572L/xx not_active Application Discontinuation
-
1990
- 1990-02-13 DK DK037890A patent/DK37890D0/da not_active Application Discontinuation
- 1990-03-28 US US07/501,869 patent/US5037970A/en not_active Expired - Fee Related
-
1992
- 1992-08-19 JP JP4220019A patent/JPH0735392B2/ja not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| J.AM.CHEM.SOC=1983 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8197729B2 (en) | 2007-10-30 | 2012-06-12 | Toyo Engineering Corporation | Method of granulation with a fluidized bed granulator |
| US8834142B2 (en) | 2007-10-30 | 2014-09-16 | Toyo Engineering Corporation | Fluidized bed granulator |
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