CA1131622A - Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine - Google Patents

Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine

Info

Publication number: CA1131622A
Authority: CA; Canada
Prior art keywords: parts; volume; acetyloxy; trimethylsilyl; naphthacenedione
Prior art date: 1978-06-05
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.): Expired

Application number

CA396,688A

Other languages

English (en)

Inventor

Raphael Pappo

Robert B. Garland

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GD Searle LLC

Original Assignee

GD Searle LLC

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.)

1978-06-05

Filing date

1982-02-19

Publication date

1982-09-14

1978-06-05 Priority claimed from US05/912,671 external-priority patent/US4161480A/en

1982-02-19 Application filed by GD Searle LLC filed Critical GD Searle LLC

1982-02-19 Priority to CA396,688A priority Critical patent/CA1131622A/fr

1982-09-14 Application granted granted Critical

1982-09-14 Publication of CA1131622A publication Critical patent/CA1131622A/fr

Status Expired legal-status Critical Current

Links

229960000908 idarubicin Drugs 0.000 title abstract description 8
239000000543 intermediate Substances 0.000 title abstract description 8
230000015572 biosynthetic process Effects 0.000 title abstract description 5
238000003786 synthesis reaction Methods 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 19
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 14
239000001257 hydrogen Substances 0.000 claims abstract description 12
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
239000002253 acid Substances 0.000 claims description 20
238000000034 method Methods 0.000 claims description 17
HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 claims description 12
JEHCHYAKAXDFKV-UHFFFAOYSA-J lead tetraacetate Chemical compound CC(=O)O[Pb](OC(C)=O)(OC(C)=O)OC(C)=O JEHCHYAKAXDFKV-UHFFFAOYSA-J 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 2
230000003647 oxidation Effects 0.000 claims 1
238000007254 oxidation reaction Methods 0.000 claims 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 abstract description 8
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound 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 abstract description 8
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STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 abstract description 8
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XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 abstract 1
229950001725 carubicin Drugs 0.000 abstract 1
230000002194 synthesizing effect Effects 0.000 abstract 1
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UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
239000000243 solution Substances 0.000 description 30
239000007787 solid Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
239000000155 melt Substances 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
229960000443 hydrochloric acid Drugs 0.000 description 13
235000011167 hydrochloric acid Nutrition 0.000 description 13
239000007983 Tris buffer Substances 0.000 description 11
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 11
230000007935 neutral effect Effects 0.000 description 11
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
239000000725 suspension Substances 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
229910007161 Si(CH3)3 Inorganic materials 0.000 description 8
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 8
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
-1 6-hydroxy-7-(trimethylsilyl)-5,12-naphthacenedione Chemical compound 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
YOFDHOWPGULAQF-MQJDWESPSA-N (7s,9s)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@@](O)(C(C)=O)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-MQJDWESPSA-N 0.000 description 5
DESHOKKWDVAXSP-WAYWQWQTSA-N (z)-4-trimethylsilylbut-3-en-2-ol Chemical compound CC(O)\C=C/[Si](C)(C)C DESHOKKWDVAXSP-WAYWQWQTSA-N 0.000 description 5
125000006519 CCH3 Chemical group 0.000 description 5
YOFDHOWPGULAQF-UHFFFAOYSA-N Daunomycin-Aglycone Natural products C1C(O)(C(C)=O)CC(O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-UHFFFAOYSA-N 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
229940022663 acetate Drugs 0.000 description 5
WIRUZQNBHNAMAB-UHFFFAOYSA-N benzene;cyclohexane Chemical compound C1CCCCC1.C1=CC=CC=C1 WIRUZQNBHNAMAB-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 4
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
150000002431 hydrogen Chemical group 0.000 description 4
229960002523 mercuric chloride Drugs 0.000 description 4
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
229960004109 potassium acetate Drugs 0.000 description 4
235000011056 potassium acetate Nutrition 0.000 description 4
239000002904 solvent Substances 0.000 description 4
QTELZWNWLZGXIE-UHFFFAOYSA-N tetracene-1,2,3,4-tetrone Chemical compound C1=CC=C2C=C(C=C3C(C(C(C(=O)C3=O)=O)=O)=C3)C3=CC2=C1 QTELZWNWLZGXIE-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
239000012259 ether extract Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000284 extract Substances 0.000 description 3
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 3
150000004682 monohydrates Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
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125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 2
IBZGBXXTIGCACK-CWKPULSASA-N Adriamycinone Chemical compound C1[C@@](O)(C(=O)CO)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O IBZGBXXTIGCACK-CWKPULSASA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
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206010028980 Neoplasm Diseases 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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235000019270 ammonium chloride Nutrition 0.000 description 2
KNCZUXHSQJQWIB-UHFFFAOYSA-N anthracene-1,4,9,10-tetrone Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(=O)C=CC2=O KNCZUXHSQJQWIB-UHFFFAOYSA-N 0.000 description 2
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229910052786 argon Inorganic materials 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
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201000011510 cancer Diseases 0.000 description 2
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238000004587 chromatography analysis Methods 0.000 description 2
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ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
229940091249 fluoride supplement Drugs 0.000 description 2
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 description 2
229930182470 glycoside Natural products 0.000 description 2
150000002338 glycosides Chemical class 0.000 description 2
229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
238000011031 large-scale manufacturing process Methods 0.000 description 2
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
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JEXINTPDRIFMGZ-AATRIKPKSA-N (e)-4-trimethylsilylbut-3-en-2-one Chemical compound CC(=O)\C=C\[Si](C)(C)C JEXINTPDRIFMGZ-AATRIKPKSA-N 0.000 description 1
QLGMGIPNUQDZIL-UHFFFAOYSA-N 1,2,3,4-tetrahydroxytetracene-5,12-dione Chemical compound C1=CC=C2C=C(C(=O)C=3C(=C(O)C(O)=C(C=3O)O)C3=O)C3=CC2=C1 QLGMGIPNUQDZIL-UHFFFAOYSA-N 0.000 description 1
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239000003810 Jones reagent Substances 0.000 description 1
101001092200 Mus musculus RNA binding protein fox-1 homolog 3 Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241001237728 Precis Species 0.000 description 1
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241000212342 Sium Species 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
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MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
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RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
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GKPOMITUDGXOSB-UHFFFAOYSA-N but-3-yn-2-ol Chemical group CC(O)C#C GKPOMITUDGXOSB-UHFFFAOYSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
230000000332 continued effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
WPJRFCZKZXBUNI-HCWXCVPCSA-N daunosamine Chemical compound C[C@H](O)[C@@H](O)[C@@H](N)CC=O WPJRFCZKZXBUNI-HCWXCVPCSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
150000002337 glycosamines Chemical class 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000010410 layer Substances 0.000 description 1
229910000464 lead oxide Inorganic materials 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
239000012071 phase Substances 0.000 description 1
HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
IKUJAIDSWVXUGG-UHFFFAOYSA-N prop-1-enyl acetate Chemical compound CC=COC(C)=O IKUJAIDSWVXUGG-UHFFFAOYSA-N 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
QXKXDIKCIPXUPL-UHFFFAOYSA-N sulfanylidenemercury Chemical compound [Hg]=S QXKXDIKCIPXUPL-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
LZPBKINTWROMEA-UHFFFAOYSA-N tetracene-5,12-dione Chemical compound C1=CC=C2C=C3C(=O)C4=CC=CC=C4C(=O)C3=CC2=C1 LZPBKINTWROMEA-UHFFFAOYSA-N 0.000 description 1
NXWNAZMGDZDNDM-UHFFFAOYSA-N tetracene-5,6,11,12-tetrone Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(=O)C1=CC=CC=C1C2=O NXWNAZMGDZDNDM-UHFFFAOYSA-N 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
QXJQHYBHAIHNGG-UHFFFAOYSA-N trimethylolethane Chemical compound OCC(C)(CO)CO QXJQHYBHAIHNGG-UHFFFAOYSA-N 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1

CA396,688A 1978-06-05 1982-02-19 Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine Expired CA1131622A (fr)

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Application Number	Priority Date	Filing Date	Title
CA396,688A CA1131622A (fr)	1978-06-05	1982-02-19	Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US05/912,671 US4161480A (en)	1978-06-05	1978-06-05	Intermediates for the synthesis of 4-demethoxydaunorubicin
US912,671		1978-06-05
CA329,030A CA1125284A (fr)	1978-06-05	1979-06-04	Produits intermediaires pour la synthese de ( )-4-demethoxydaunorubicine
CA396,688A CA1131622A (fr)	1978-06-05	1982-02-19	Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine

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CA1131622A true CA1131622A (fr)	1982-09-14

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CA396,688A Expired CA1131622A (fr)	1978-06-05	1982-02-19	Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10144753B2 (en)	2012-10-15	2018-12-04	Produkem Molekulares Design Gmbh	Anthracycline derivatives for treating tumor diseases

1982
- 1982-02-19 CA CA396,688A patent/CA1131622A/fr not_active Expired

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10144753B2 (en)	2012-10-15	2018-12-04	Produkem Molekulares Design Gmbh	Anthracycline derivatives for treating tumor diseases

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Date	Code	Title	Description
1999-09-14	MKEX	Expiry
2023-05-26	MKEX	Expiry	Effective date: 19990914

Publication	Publication Date	Title
JPH06172302A (ja)	1994-06-21	１９−ノルビタミンｄ化合物の調製
CA1125284A (fr)	1982-06-08	Produits intermediaires pour la synthese de ( )-4-demethoxydaunorubicine
Barton et al.	1978	Synthesis and thermochemistry of 4-diazo-1, 1-dimethyl-1-silacyclohexa-2, 5-diene
US4064181A (en)	1977-12-20	Preparation of novel ethers
CA1131622A (fr)	1982-09-14	Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine
Kanemasa et al.	1985	Diene-transmissive Diels-Alder Reaction Using 2-Ethoxy-3-methylene-1, 4-pentadiene and 2-(2-Bromo-1-ethoxyethyl) 1, 3-butadiene
Marchand et al.	1984	Heptacyclo [5.5. 1.14, 10.02, 6.03, 11.05, 9.08, 12] tetradecane-13, 14-dione: a novel, polycyclic perpendobiplanar D2d diketone
JPH0639468B2 (ja)	1994-05-25	ヒドロキノン誘導体
Kimura et al.	1986	A simple and efficient synthesis of optically active (+)-4-demethoxydaunomycinone.
Sanchez et al.	1994	Phenol Benzylic Epoxide to Quinone Methide Electron Reorganization: Synthesis of (.+-.)-Taxodone
EP0013082B1 (fr)	1982-12-15	Procédé de préparation de stéroides ayant un groupe cétonique dans la chaîne latérale
US4021478A (en)	1977-05-03	Preparation of carboxylic acids from glycidonitriles with ionic lewis acids
JPS645034B2 (fr)	1989-01-27
Tang et al.	2005	The study of intramolecular tandem radical cyclizations of acylsilanes with radicalphiles attached on silicon
CA1131623A (fr)	1982-09-14	Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine
US4077996A (en)	1978-03-07	Process for the preparation of trans-deca hydronaphthalene derivatives
US4124648A (en)	1978-11-07	Process for the preparation of norpatchoulenol and intermediates therefor
US4181683A (en)	1980-01-01	1,7-Octadien-3-one and process for preparing the same
Niwa et al.	1976	Chemical correlations of α-santonin with (+)-junenol and acolamone
US4914220A (en)	1990-04-03	Process for synthesis of E-2-methyl-α,β-unsaturated aldehydes
EP0387929B1 (fr)	1994-04-27	Dérivés triméthylsilyl d'acétylène, leur préparation et leur utilisation pour la préparation de dérivés de daunomycinone
Loozen et al.	1976	A facile and stereoselective approach to geminal endo‐iodo‐exo‐bromocyclopropanes; application in the synthesis of medium‐sized rings
Ishimaru et al.	2001	Diastereoselective Synthesis of trans-N-Benzyl-2-(2-methylphenyl)-6-phenyl-4-piperidone
Dehmlow et al.	1992	Dioxa-cage and bridged compounds as possible precursors for tricyclo [5.5. 0.04, 10] dodeca-2, 5, 8, 11-tetraene
JPS61152665A (ja)	1986-07-11	六置換ベンゼン誘導体

CA1131622A - Produits intermediaires pour la synthese de (.sup. )-4-demethoxydaunorubicine - Google Patents

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ID=27166277

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