AP750A - Method for preparing 4,10-diacetoxy-2a-benzoyloxy-5b, 20-epoxy-1, 7b-dihydroxy-9-oxo-tax-11-en-13a-y) (2r,3s) -3-benzoylamono-2-hydroxy-3-Phenylpropionate trihydrate. - Google Patents
Method for preparing 4,10-diacetoxy-2a-benzoyloxy-5b, 20-epoxy-1, 7b-dihydroxy-9-oxo-tax-11-en-13a-y) (2r,3s) -3-benzoylamono-2-hydroxy-3-Phenylpropionate trihydrate. Download PDFInfo
- Publication number
- AP750A AP750A APAP/P/1997/001035A AP9701035A AP750A AP 750 A AP750 A AP 750A AP 9701035 A AP9701035 A AP 9701035A AP 750 A AP750 A AP 750A
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- AP
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- Prior art keywords
- hydroxy
- diacetoxy
- benzoyloxy
- dihydroxy
- epoxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002425 crystallisation Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- HYJVYOWKYPNSTK-UONOGXRCSA-N (2r,3s)-3-benzamido-2-hydroxy-3-phenylpropanoic acid Chemical compound N([C@H]([C@@H](O)C(O)=O)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 HYJVYOWKYPNSTK-UONOGXRCSA-N 0.000 claims description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- RRGNLQYIUYOTQC-LQFAMLORSA-N (2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoic acid trihydrate Chemical compound O.O.O.C(C1=CC=CC=C1)(=O)N[C@H]([C@H](C(=O)O)O)C1=CC=CC=C1 RRGNLQYIUYOTQC-LQFAMLORSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 4
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- VOFNTYSIOLSAMB-UHFFFAOYSA-N phenyl propanoate trihydrate Chemical compound O.O.O.C1(=CC=CC=C1)OC(CC)=O VOFNTYSIOLSAMB-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 229930014667 baccatin III Natural products 0.000 claims description 2
- RZARFIRJROUVLM-GVHYBUMESA-N (3r)-3-amino-2-hydroxy-3-phenylpropanoic acid Chemical class OC(=O)C(O)[C@H](N)C1=CC=CC=C1 RZARFIRJROUVLM-GVHYBUMESA-N 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 abstract description 4
- 229960001592 paclitaxel Drugs 0.000 abstract description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract description 4
- 150000004684 trihydrates Chemical class 0.000 abstract description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000004593 Epoxy Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- RDVJYGYJBUIIOE-ZOAFEQKISA-N (4s,5r)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1N(C(=O)C=2C=CC=CC=2)[C@@H](C=2C=CC=CC=2)[C@H](C(O)=O)O1 RDVJYGYJBUIIOE-ZOAFEQKISA-N 0.000 description 1
- YWLXLRUDGLRYDR-SKXCCXORSA-N 10-dab iii Chemical compound O([C@H]1C2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-SKXCCXORSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 241001116498 Taxus baccata Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- POALUPLKPJWUJR-UHFFFAOYSA-N phenyl 1,3-oxazolidine-5-carboxylate Chemical compound O=C(Oc1ccccc1)C1CNCO1 POALUPLKPJWUJR-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical group C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A method for preparing by crystallisation from a water/alcohol solution of the trihydrate of paclitaxel of formula:
Description
ORIGINAL
PROCESS FOR THE PREPARATION OF 4,10-DIACETQXY2or-BENZOYLOXY-5g, 20-EPOXY-1 , 7ff-PIHYDROXY-9.-OXOTAX-ll-EN-13oi-YL (2R, 3S) -3-BENZOYLAMINO-2HYDROXY-3-PHENYLPROPIONATE TRIHYDRATE
The present invention relates to a process for the preparation of 4 , lO-diacetoxy-Por-benzoyloxyS/S, 20-epoxy-l, 7/3-dihydroxy-9-oxotax-11 -en- 13a-yl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropionate trihydrate .
4,10-Diacetoxy-2a-benzoyloxy-5/S, 20-epoxy1,7/3-dihydroxy-9-oxotax-ll-en-13cr-yl (2R,3S) -3benzoylamino-2-hydroxy-3-phenylpropionate (or t
paclitaxel) has noteworthy anticancer and antileukaemia properties .
4 ,10 - Diace toxy-2 a-benz oy loxy - 5/3, 20-epoxy1,7/3-dihydroxy-9-oxotax-ll-en-13ar-yl (2R,3S) -3benzoylamino-2-hydroxy-3-phenylpropionate may either be isolated from yew bark or prepared from baccatin III or from 10-desacetylbaccatin III according to the processes which are described more particularly in European patent applications EP 0,336,840 or EP 0,400,971 or in PCT international application WO
94/07378.
It has been found that 4,10-diacetoxy-2a25 benzoyloxy-5/S,20-epoxy-l, 7/S-dihydroxy-9-oxo tax-11-en13a-yl (2R,3£)-3-benzoylamino-2-hydroxy-3phenylpropionats trihydrate hss a stability which is
AP/P/ 97/01035
AP . Ο Ο 7 5 Ο markedly superior to that of the anhydrous product.
According to the invention, 4,10-diacetoxy2a-benzcyloxy- 5/3, 2 0 - epoxy-1,7/5-dihydroxy - 9-oxotax-11en-13oi-yl (2R, 3S) - 3-benzoylamino-2 -hydroxy-3 5 phenylpropionate trihydrate may be obtained after' crystallization of 4,10 - diacetoxy-2o:-benzoyloxy-5/5, 20epoxy-l,7β-dihydroxy-9 -oxotax-11-en-13a-yl (2R,3S)-3benzoylamino-2-hydroxy-3-phenylpropionate from a mixture of water and an aliphatic alcohol containing 1 to 3 carbon atoms, followed by drying of the product obtained then is dried under reduced pressure and then maintained in a relative humidity of greater than 20% at a temperature in the region of 25 °C.
In order to carry out the process according to the invention, it may be particularly advantageous
- to dissolve or suspend the 4,10-diacetoxy-2ofbenzoyloxy - 5/3, 2 0 - epoxy-1,7 β- dihydroxy- 9 - oxo tax-11 - en13o:-yl (2R, 3S) -3-benzoylamino-2-hydroxy-3 phenylpropionate in an aliphatic alcohol containing 1 to 3 carbon atoms,
- to treat the solution or the suspension with water optionally containing an inorganic base such as sodium hydrogen carbonate,
- to separate the crystals obtained, then
- to dry them under reduced pressure, and then
- optionally to maintain them in an atmosphere whose relative humidity is greater than 20% at a temperature in the region of 25 °C.
AP/P/ 9 7 / 0 1 0 3 5
AP .0 0 7 5 0
Generally, the 4,10-diacetoxy-2a:-beiizoyloxy5,3,20 - epoxy-1,7/3- dihydroxy - 9 - oxo tax -11- en-13or-yl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropionate is di BEolved in an excess of the aliphatic alcohol, preferably methanol. The amount of alcohol is preferably between 6 and 12 parts by weight relative to the 4,10-diacetoxy-2n-benzoyloxy-5/3, 2 0-epoxy-l, Ί βdihydroxy-9-oxotax-ll-en-13a-yl (2R,3S)-3-benzoylamino2-hydroxy-3-phenylpropionate used.
Generally, water is added such that the water/alcohol weight ratio is between 3/1 and 1/3. The water added may contain up to 10% (w/v) of an inorganic base such as sodium hydrogen carbonate, so that the pH of the reaction mixture is above or equal to 7, preferably between 7 and 8, before separation of the crystals .
The 4,10-diacetoxy-2a-benzoyloxy-5β,20-epoxy1, Ίβ-dihydroxy-9-oxotax-11-en-13ff-yl (2R,3S)-3benzoylamino-2-hydroxy-3-phenylpropionate trihydrate which crystallizes is separated out, preferably by filtration or centrifugation, and then dried. The drying is carried out under reduced pressure, between 1 and 7 kPa, at a temperature in the region of 40 °C and the product obtained is optionally maintained in an atmosphere whose relative humidity is greater than 20% and at a temperature of between 0 and 60°C, preferably in the region of 25°C.
In order to carry out the process, it may be
AP/P/ 9 7 / 0 1 0 3 5
AP.00750 advantageous to perform the crystallization in the presence of ascorbic acid which is added during the dissolution or suspending of the 4,10-diacetoxy-2abenzoyloxy-5/3, 20- epoxy-1, Ί β- dihydroxy- 9 -oxo tax-11-en13a-yl (2R,3S)-3-benzoylamino-2-hydroxy-3 phenylpropionate in the alcohol. It is possible to use up to 1% by weight of ascorbic acid.
4,10 -Diacetoxy-2a-benzoyloxy-5/3, 20-epoxy1,7/S-dihydroxy-9-oxotax- 11-en- 13cf-yl (2R,3S) -3benzoylamino-2-hydroxy-3-phenylpropionate trihydrate has been studied by thermogravimetrie and differential calorimetric analyses and by X-ray diffraction.
More particularly, the thermogravimetrie e
analysis shows a loss of mass between 25 and 140°C in the region of 6%, which corresponds to three molecules of water per one molecule of 4,10-diacetoxy-2abenzoyloxy- 5/5, 20 - epoxy-1,7/3-dihydroxy-9 - oxotax - 11-en13of-yl {2R, 3S) -3-benzoylamino-2 -hydroxy-3phenylpropionate.
In order to carry out the process according to the invention, when semi-synthetic paclitaxel is used, which is obtained according to the processes described, for example, in European patents EP 0,336,840 or EP 0,400,971 or in PCT international application WO 94/07878 which lead to a paclitaxel intermediate whose hydroxyl functions are protected, it is possible to work directly on the 4,10-diacetoxy-2abexizoyloxy-5β, 20-epoxy-1,7,5-dihydroxy-9-oxo tax-ll-enir κ
c τ*
C r*· c
Q
Q <
AP.00750
13cK-yl (2R, 3S) -3 -benzoylamino-2 - hydroxy-3 phenylpropionate solution or suspension obtained after removal of the protecting groups from the hydroxyl functions of the taxane ring and of the side chain. For example, by working under the conditions of PCT international application WO 94/07878, the intermediate
4,10 - diace toxy- 2a-b enzoy loxy- 5/3,2 0 - epoxy-1-hydroxy-Ίβfcriethylsilyloxy-9-oxotax-ll-en-13ar-yl (4S, 5R) -3benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-510 carboxylate is obtained in which the protecting groups may be removed using trifluoroacetic acid in methanol.
The examples which follow illustrate the present invention.
EXAMPLE 1 t
5.014 g of 4,10-diacetoxy-2a-benzoyloxy5)3,20 - epoxy-1-hydroxy-7β-triethylsilyloxy-9-oxotax-11en-13a-yl (4S,5R)-3-benzoyl-2-{4-methoxyphenyl)-4phenyl-1,3-oxazolidine-5-carboxylate assaying at 98% (4.52 mmol) and 50 cm3 of methanol are introduced into a reactor sheltered from the light. 7 cm3 of trifluoroacetic acid are added rapidly to the stirred white suspension. The temperature rises to about 35°CAfter cooling to a temperature of about 5 °C, 110 cm3 of agueous 6% (w’/v) sodium hydrogen carbonate solution are ’added. The pH is equal to 7. The crystals are separated out by filtration on a sinter funnel and are washed with 4 times 15 cm3 of a methanol/water mixture (30/70 by volume). After drying under reduced pressure at
AP/P/ 9 7 / 0 1 0 3 5
AP 00750
35°C, 3.676 g of 4,10-diacetoxy-2a-benzoyloxy-5/3,20epoxy-1,7/3-dihydroxy-9 - oxotax-11-en-13a-yl (2R, 3S)-3 benzoylanino-2-hydroxy-3-phenylpropionate assaying at 93.1% and containing about 4.8% water are obtained.
The yield of pure product is 89.3% relative to the ester used.
When maintained under relative humidity conditions of greater than 20%, the product stabilizes with a water content of about 6%. The XRPD diagram b
(X-ray powder diagram) shows that the product thus obtained is in the form of a trihydrate (theoretical *
value of the water content in the 4,10-diacetoxy-2of- c benzoyloxy-5/3, 20-epoxy - 1,7/3-dihydroxy-9-oxotax-11-enβ
13α-yl (2R,3S)-3-benzoylamino-2-hydroxy-3 15 phenylpropionate trihydrate of 5.95%).
EXAMPLE 2
3.006 g of 4,10-diacetoxy-2a-benzoyloxy5/3,20 -epoxy -1-hydroxy-7/3-tri ethyl si lyloxy-9-oxo tax-lien-13o;-yl (4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-420 phenyl-1,3-oxazolidine-5-carboxylate assaying at 98% (2.70 mmol) and 30 cm3 of'methanol are introduced into a reactor sheltered from the light. 6.3 cm3 of 99% trifluoroacetic acid are added to the stirred white suspension. After cooling to a temperature of about
5°C, 7.5 cm3 of demineralized water are added over 15 minutes. The crystals are separated out by filtration on a sinter funnel and are washed with 3 times 5 cm3 of a methanol/water mixture (80/20 by volume) at 5°C.
Α Ο/Π/ Λ -7
AP . Ο 0 7 5 0
After drying under reduced pressure at 35°C, 1.989 g of
4,10 -diacetoxy- 2o,-benzoyloxy- 5/5, 2 0 - epoxy-1,7/5dihydroxy-9-oxotax-ll-en-13of-yl (2R., 33) -3 -benzoylamino2-hydroxy-3-phenylpropionate are obtained, assaying at
97.8% and containing about 6.8% water.
The yield is 84.3% relative to the ester used.
AP/P/ 9 7 / 0 1 0 3 5
AP . 00750
Claims (5)
1. Process for the preparation of 4,10diacetoxy-2a-benzoyloxy-5/7,2 0 - epoxy-1,7/3-dihydroxy- 9 oxotax-ll-en-13a-yl (2R,3S)-3-benzoylamino-2-hydroxy-3 5 phenylpropionate trihydrate, characterized in that
4,10 -diacetoxy- 2a-benzoyloxy-5)8, 2 0 - epoxy-1,7/7dihydroxy-9-oxotax-ll-en-13a-yl (2R,3S)-3-benzoylamino2-hydroxy-3-phenylpropionate is crystallized from a mixture of water and an aliphatic alcohol containing 1
10 to 3 carbon atoms, then the product obtained is dried under reduced pressure and then optionally maintained under relative humidity conditions of greater than 20%.
2. Process according to Claim 1, characterized in that the water/alcohol weight ratio is
15 between 3/1 and 1/3.
3. Process according to either of Claims 1 and 2, characterized in that the alcohol is methanol.
4. Process according to Claim 1, characterized in that the drying is carried out at a
20 temperature in the region of 40°C under reduced pressure and that the product stabilizes at about 6% water in an atmosphere in which the relative humidity is greater than 20%.
5. Process according to Claim. 1,
25 characterized in that the crystallization is carried out in the presence of ascorbic acid.
5. Process according to Claim 1, characterized in that the process is performed directly
AP/PZ 97/01015
AP . Ο Ο 7 5 Ο in situ on the ester resulting from the esterification of baccatin III, whose 13-hydroxy function is protected, with a protected β-phenylisoserine derivative after removal of the protecting groups.
5 7. 4,10-Diacetoxy-2a-benzoyloxy-5/3,20epoxy-1,7/3-dihydroxy-9 -oxotax-11-en-13a-yl (2R,3S)-3benzoylamino-2 -hydroxy-3-phenylpropionate trihydrate.
AP/P/ 9 7 / 0 1 0 3 5
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9500816A FR2729666A1 (en) | 1995-01-25 | 1995-01-25 | PROCESS FOR THE PREPARATION OF (2R, 3S) TRIHYDRATE - BENZOYLAMINO-2-HYDROXY-3-PHENYLPROPIONATE OF 4,10-DIACETOXY- 2ALPHA-BENZOYLOXY-5BETA, 20-EPOXY-1,7BETA-DIHYDROXY-9-OX 11-EN-13ALPHA-YLE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9701035A0 AP9701035A0 (en) | 1997-07-31 |
| AP750A true AP750A (en) | 1999-07-06 |
Family
ID=9475464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1997/001035A AP750A (en) | 1995-01-25 | 1996-01-23 | Method for preparing 4,10-diacetoxy-2a-benzoyloxy-5b, 20-epoxy-1, 7b-dihydroxy-9-oxo-tax-11-en-13a-y) (2r,3s) -3-benzoylamono-2-hydroxy-3-Phenylpropionate trihydrate. |
Country Status (43)
| Country | Link |
|---|---|
| US (1) | US6002022A (en) |
| EP (1) | EP0805806B1 (en) |
| JP (1) | JP3782449B2 (en) |
| KR (1) | KR100384773B1 (en) |
| CN (1) | CN1067997C (en) |
| AP (1) | AP750A (en) |
| AT (1) | ATE187719T1 (en) |
| AU (1) | AU707603B2 (en) |
| BG (1) | BG62769B1 (en) |
| BR (1) | BR9606853A (en) |
| CO (1) | CO4700286A1 (en) |
| CZ (1) | CZ287079B6 (en) |
| DE (1) | DE69605651T2 (en) |
| DK (1) | DK0805806T3 (en) |
| DZ (1) | DZ1977A1 (en) |
| EE (1) | EE03396B1 (en) |
| ES (1) | ES2139332T3 (en) |
| FI (1) | FI119245B (en) |
| FR (1) | FR2729666A1 (en) |
| GE (1) | GEP19991833B (en) |
| GR (1) | GR3032110T3 (en) |
| HU (1) | HU223352B1 (en) |
| IL (1) | IL116903A (en) |
| IN (1) | IN184427B (en) |
| IS (1) | IS2033B (en) |
| MA (1) | MA23782A1 (en) |
| MY (1) | MY113230A (en) |
| NO (1) | NO316987B1 (en) |
| NZ (1) | NZ300958A (en) |
| OA (1) | OA10438A (en) |
| PE (1) | PE64896A1 (en) |
| PL (1) | PL183773B1 (en) |
| PT (1) | PT805806E (en) |
| RO (1) | RO115728B1 (en) |
| RU (1) | RU2154642C2 (en) |
| SK (1) | SK281958B6 (en) |
| TN (1) | TNSN96011A1 (en) |
| TR (1) | TR199700676T1 (en) |
| TW (1) | TW356469B (en) |
| UA (1) | UA47420C2 (en) |
| UY (1) | UY24149A1 (en) |
| WO (1) | WO1996022984A1 (en) |
| ZA (1) | ZA96523B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL203300B1 (en) * | 2000-10-31 | 2009-09-30 | Akad Medyczna | Stable pharmacological form of anticarcinogenic drug and method of obtaining such drug in that form |
| US6891050B2 (en) * | 2001-08-10 | 2005-05-10 | Dabur India Limited | Process for the preparation of taxanes such as paclitaxel, docetaxel and structurally similar analogs |
| US6894456B2 (en) | 2001-11-07 | 2005-05-17 | Quallion Llc | Implantable medical power module |
| US6881852B2 (en) * | 2002-02-05 | 2005-04-19 | Dabur India Limited | Process of purification of paclitaxel and docetaxel |
| US7247738B2 (en) * | 2002-05-07 | 2007-07-24 | Dabur India Limited | Method of preparation of anticancer taxanes using 3-[(substituted-2-trialkylsilyl) ethoxycarbonyl]-5-oxazolidine carboxylic acids |
| US6900342B2 (en) * | 2002-05-10 | 2005-05-31 | Dabur India Limited | Anticancer taxanes such as paclitaxel, docetaxel and their structural analogs, and a method for the preparation thereof |
| US6838569B2 (en) * | 2002-12-16 | 2005-01-04 | Dabur India Limited | Process for preparation of paclitaxel trihydrate and docetaxel trihydrate |
| EP1947094A3 (en) | 2003-12-12 | 2009-02-18 | Quiral Quimica Do Brasil | Process for the preparation of taxane derivatives |
| CN100420681C (en) * | 2005-04-29 | 2008-09-24 | 上海奥锐特国际贸易有限公司 | Production of polyenoic taxad alcohol trihydrate |
| WO2009137084A2 (en) * | 2008-05-07 | 2009-11-12 | Ivax Research, Llc | Processes for preparation of taxanes and intermediates thereof |
| US8633240B2 (en) * | 2012-06-01 | 2014-01-21 | The University Of Utah Research Foundation | Paclitaxel trihydrates and methods of making thereof |
| CN103833693B (en) * | 2014-03-04 | 2016-02-24 | 悦康药业集团有限公司 | A kind of taxol compound and the pharmaceutical composition containing this taxol compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1994021662A1 (en) * | 1993-03-15 | 1994-09-29 | Yale University | Diagnosis of human inflammatory bowel diseases and nucleic acid reagents therefor |
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| FR2703049B1 (en) * | 1993-03-22 | 1995-04-21 | Rhone Poulenc Rorer Sa | Method for the purification of taxoids. |
| CA2163837C (en) * | 1994-12-13 | 1999-07-20 | Robert K. Perrone | Crystalline paclitaxel hydrates |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1994021662A1 (en) * | 1993-03-15 | 1994-09-29 | Yale University | Diagnosis of human inflammatory bowel diseases and nucleic acid reagents therefor |
Non-Patent Citations (1)
| Title |
|---|
| CHEMICAL ABSTRACTS, vol. 113, no. 75, 1990 Columbus, Ohio, US; abstract no. 14264k, GUERITE-VOEGELEIN ET AL. "STRUCTURE OF A SYNTHETIC TAXOL PRECURSOR." PAGE 723; & ACTA CRYSTALLOGR. SECT. C: CRYST. STRUCT. COMM., vol C46, no. 5, 1990 ENGL., pages 781-784 * |
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