CA1046508A - Process for the preparation of daunomycins - Google Patents
Process for the preparation of daunomycinsInfo
- Publication number
- CA1046508A CA1046508A CA222,610A CA222610A CA1046508A CA 1046508 A CA1046508 A CA 1046508A CA 222610 A CA222610 A CA 222610A CA 1046508 A CA1046508 A CA 1046508A
- Authority
- CA
- Canada
- Prior art keywords
- trifluoroacetyl
- chloro
- bis
- daunosamine
- epi
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 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 claims abstract description 11
- 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 claims abstract description 11
- 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 claims abstract description 8
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 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 claims abstract description 8
- STQGQHZAVUOBTE-HQXHJQOISA-N (7s,9s)-9-acetyl-7-[(2r,4r,5s,6r)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione 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-HQXHJQOISA-N 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 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
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 3
- 238000009835 boiling Methods 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 229960001701 chloroform Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- WPJRFCZKZXBUNI-HCWXCVPCSA-N daunosamine Chemical class C[C@H](O)[C@@H](O)[C@@H](N)CC=O WPJRFCZKZXBUNI-HCWXCVPCSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 150000002402 hexoses Chemical class 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940101209 mercuric oxide Drugs 0.000 description 3
- NGYIMTKLQULBOO-UHFFFAOYSA-L mercury dibromide Chemical compound Br[Hg]Br NGYIMTKLQULBOO-UHFFFAOYSA-L 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 101100421901 Caenorhabditis elegans sos-1 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GUGHGUXZJWAIAS-QQYBVWGSSA-N Daunorubicin hydrochloride Chemical compound Cl.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 GUGHGUXZJWAIAS-QQYBVWGSSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 238000006994 Koenigs-Knorr glycosidation reaction Methods 0.000 description 1
- 241000713862 Moloney murine sarcoma virus Species 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 231100000457 cardiotoxic Toxicity 0.000 description 1
- 230000001451 cardiotoxic effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000008266 deoxy sugars Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- -1 temperature Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1225474A GB1457559A (en) | 1974-03-20 | 1974-03-20 | Daunomycins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1046508A true CA1046508A (en) | 1979-01-16 |
Family
ID=10001195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA222,610A Expired CA1046508A (en) | 1974-03-20 | 1975-03-20 | Process for the preparation of daunomycins |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS5833880B2 (en, 2012) |
| AT (1) | AT338419B (en, 2012) |
| BE (1) | BE826848A (en, 2012) |
| CA (1) | CA1046508A (en, 2012) |
| CH (1) | CH615198A5 (en, 2012) |
| DE (1) | DE2510926C3 (en, 2012) |
| DK (1) | DK146541C (en, 2012) |
| FR (1) | FR2264554B1 (en, 2012) |
| GB (1) | GB1457559A (en, 2012) |
| NL (1) | NL176636C (en, 2012) |
| SE (1) | SE434843B (en, 2012) |
| SU (1) | SU589926A3 (en, 2012) |
| ZA (1) | ZA751687B (en, 2012) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6087340A (en) * | 1985-08-02 | 2000-07-11 | Pharmacia & Upjohn, Inc. | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
| US6107285A (en) * | 1985-08-02 | 2000-08-22 | Pharmacia & Upjohn Company | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2678274A1 (fr) * | 1991-06-25 | 1992-12-31 | Medgenix Group Sa | N-leucyl epirubicine application a titre de medicament antitumoral et procede de preparation. |
-
1974
- 1974-03-20 GB GB1225474A patent/GB1457559A/en not_active Expired
-
1975
- 1975-03-13 DE DE2510926A patent/DE2510926C3/de not_active Expired
- 1975-03-14 NL NLAANVRAGE7503079,A patent/NL176636C/xx not_active IP Right Cessation
- 1975-03-17 AT AT202875A patent/AT338419B/de not_active IP Right Cessation
- 1975-03-18 SU SU752129602A patent/SU589926A3/ru active
- 1975-03-18 SE SE7503084A patent/SE434843B/xx not_active IP Right Cessation
- 1975-03-18 ZA ZA00751687A patent/ZA751687B/xx unknown
- 1975-03-18 DK DK109275A patent/DK146541C/da not_active IP Right Cessation
- 1975-03-19 BE BE154470A patent/BE826848A/xx not_active IP Right Cessation
- 1975-03-19 JP JP50033493A patent/JPS5833880B2/ja not_active Expired
- 1975-03-19 FR FR7508547A patent/FR2264554B1/fr not_active Expired
- 1975-03-19 CH CH352975A patent/CH615198A5/de not_active IP Right Cessation
- 1975-03-20 CA CA222,610A patent/CA1046508A/en not_active Expired
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6087340A (en) * | 1985-08-02 | 2000-07-11 | Pharmacia & Upjohn, Inc. | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
| US6107285A (en) * | 1985-08-02 | 2000-08-22 | Pharmacia & Upjohn Company | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
| US6284738B1 (en) | 1985-08-02 | 2001-09-04 | Pharmacia & Upjohn Company | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
| US7005421B2 (en) | 1985-08-02 | 2006-02-28 | Pharmacia & Upjohn Company | Injectable ready-to-use solutions containing an antitumor anthracycline glycoside |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA751687B (en) | 1976-02-25 |
| JPS5833880B2 (ja) | 1983-07-22 |
| DK146541B (da) | 1983-10-31 |
| DE2510926C3 (de) | 1980-03-13 |
| ATA202875A (de) | 1976-12-15 |
| NL7503079A (nl) | 1975-09-23 |
| DE2510926A1 (de) | 1975-09-25 |
| FR2264554B1 (en, 2012) | 1978-07-28 |
| FR2264554A1 (en, 2012) | 1975-10-17 |
| GB1457559A (en) | 1976-12-08 |
| SU589926A3 (ru) | 1978-01-25 |
| NL176636C (nl) | 1985-05-17 |
| BE826848A (fr) | 1975-09-19 |
| DK109275A (en, 2012) | 1975-09-21 |
| CH615198A5 (en) | 1980-01-15 |
| SE7503084L (en, 2012) | 1975-09-22 |
| NL176636B (nl) | 1984-12-17 |
| AT338419B (de) | 1977-08-25 |
| AU7919775A (en) | 1976-09-23 |
| JPS50126657A (en, 2012) | 1975-10-04 |
| SE434843B (sv) | 1984-08-20 |
| DK146541C (da) | 1984-04-09 |
| DE2510926B2 (de) | 1979-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4039663A (en) | Daunomycins, process for their uses and intermediates | |
| US4058519A (en) | Adriamycins and uses thereof | |
| US4112076A (en) | Epi-daunomycin and epi-adriamycin compounds and method of use | |
| US4046878A (en) | Daunomycin analogues, their preparation and use | |
| CA1099705A (en) | Process for the preparation of new daunomycin derivatives and their aglycones | |
| US4987126A (en) | 3'-deamino-4'-deoxy-4'-amino anthracyclines | |
| US4188377A (en) | Carminomycin derivatives, their preparation and use | |
| US4025623A (en) | 4'-Epi-6'-hydroxyadriamycin and method of use | |
| US4325946A (en) | Anthracycline glycosides, their preparation, use and compositions thereof | |
| CA1046508A (en) | Process for the preparation of daunomycins | |
| EP0199920B1 (en) | New antitumor anthracyclines | |
| US4393052A (en) | Antitumor anthracycline glycosides, their preparation, intermediates therefor, and compositions and use thereof | |
| US4839346A (en) | Antitumor anthracycline glycosides, intermediates thereof, and composition and use thereof | |
| US4183919A (en) | Antitumor glycosides, process for their preparation including intermediates therefor and their use | |
| US4267116A (en) | Novel daunomycin derivatives, their aglycones and the use thereof | |
| US4322412A (en) | Anthracycline glycosides, their preparation, use and compositions thereof | |
| CA1080702A (en) | Process for the preparation of disaccharide, analogs of antitumor anthracyclines | |
| US4216157A (en) | Substituted antitumor anthracyclines | |
| US4131649A (en) | Daunorubicin derivatives, their preparation and their use | |
| US4522815A (en) | Anthracycline glycosides | |
| DE3905431A1 (de) | Neue 4-demethyl-4-0-(p-fluorobenzolsulfonyl)anthracyclinglycoside | |
| US4098798A (en) | Adriamycins, process for their preparation and uses thereof | |
| US4276289A (en) | Antitumor glycosides, their preparation and use | |
| GB2034707A (en) | Anthracycline glycosides | |
| EP0639581A1 (en) | Anthracycline antibiotics |