CN108069999A - A kind of synthetic method of taxanes intermediate - Google Patents
A kind of synthetic method of taxanes intermediate Download PDFInfo
- Publication number
- CN108069999A CN108069999A CN201810079487.5A CN201810079487A CN108069999A CN 108069999 A CN108069999 A CN 108069999A CN 201810079487 A CN201810079487 A CN 201810079487A CN 108069999 A CN108069999 A CN 108069999A
- Authority
- CN
- China
- Prior art keywords
- taxanes
- synthetic method
- reaction
- intermediate compound
- compound
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
-
- 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
Abstract
The present invention provides a kind of taxanes intermediate compound I, the synthetic methods of II, belong to pharmaceutical synthesis field.The synthetic method of taxanes intermediate compound I includes：Under protective gas atmosphere, make 4 phenyl of (3R, 4S) 1 (4 anisyl) 3 hydroxyl, 2 aza cyclo-butanone and 1, nucleophilic substitution occurs for 5 pairs of (halogenated diisopropyl silylation) pentanes.The synthetic method of taxanes intermediate II includes：Above-mentioned obtained taxanes intermediate compound I is taken off into PMB protecting groups with ammonium ceric nitrate, obtains compound III；The compound III and dimethyl dicarbonate butyl ester are subjected to amido protecting reaction.The reaction condition of the synthetic method is mild, at low cost, and environmentally friendly, obtained taxanes intermediate, and ee values are high, purity is big, high income, and the synthesis of taxone can be used for as chiral side chain.
Description
Technical field
The present invention relates to pharmaceutical synthesis field, in particular to a kind of synthetic method of taxanes intermediate.
Background technology
At present, cancer has become the principal disease for endangering human health, according to the statistics of WHO, global cancer patient
There are about 76,000,000 people, the death rate is up to 128.58/10 ten thousand.Meanwhile cancer causes great economic loss to society, for this purpose, doctor
Medicine circle has put into huge manpower and financial resources.Taxone is as broad-spectrum anti-tumor medicine, due to having the effect of notable, city
Field occupation rate is in ascendant trend, annual sales amount also show the situation of rapid growth year by year.2000 annual sales revenues are more than 100,000,000 beautiful
Member, 2002 annual sales amounts have reached 500,000,000 dollars.The price of international market docetaxel is about 12~150,000 dollars/kilogram, and 2005
Year, the sales volume of docetaxel and paclitaxel api will be more than antineoplastic total value in seven big medical market of the world
10%, reach 2,500,000,000 dollars or more." taxotere " sales volume of French Sanofi-Aventis company in 2010 is up to 21.22 hundred million
Euro." Docetaxel " of Hengrui Medicine Co., Ltd., Jiangsu Prov. in 2010 occupies 38.81% domestic market share, although
It is declined slightly, but still tops the list, " taxotere " of French Sanofi-Aventis and " Docetaxel " of Qilu Pharmaceutical Factory point row
2nd, three, the front three market share is up to 88.49%, and the market concentration is higher.Cabazitaxel, as one after taxol and
Granted taxone after docetaxel, has anti-prostate cancer better effects, and indication may further expand.
It may be because prostate-cancer incidence has surmounted lung cancer in the male cancer patient of European and American areas, rank first place, FDA accelerates to examine
The kind has been criticized, and has ratified to list in the U.S..
Therefore, taxone has become the kind that businessman has an optimistic view of, and it is most potential will to become anti-tumor chemotherapeutic market
One of drug.Successfully develop taxone new process, improve product quality and yield, reduce production cost establish by
Its basis introduced to the market will generate huge economic benefit and social benefit.
Taxanes is isolated anti-tumor active ingredient from plant, and the chemical combination of the active ingredient to having obtained
Object carries out structural modification, a series of derivatives of synthesis.Taxone mainly include taxol, docetaxel, kappa he
Match and the derivative with taxane-skeleton structure.Natural products taxol is by being extracted in plant yewtree bark
The effective antitumor ingredient gone out, docetaxel, Cabazitaxel are precursor (the taxanes mothers by being extracted in european yew needle
Ring) through semi-synthetic product.
Since natural Japanese yew alcohol extracting is extremely inefficient, the synthesis of taxone is main still from 10- deacetylates bar
The taxaneses female rings such as card booth III (10-DAB) are set out, and are coupled with chiral side chain, are obtained using a series of processing.Taxanes
Female ring and the price of chiral side chain are the critical components of the production of raw medicine, and cost accounting is high.And taxanes female ring is day
Right extract, therefore, if can by low cost, low environment pollution in a manner of synthesis of chiral side chain, will be synthesized in taxone
Middle acquisition great advantage.
WO2007051306A1 and WO2014072996A2 report respectively using the chiral lactam containing leaving group as
Key intermediate is the method for 13 side chain donors, and the taxone that is used for that 13 side chains are a very advantageous synthesizes
Chiral side chain.But it is had not been reported for wherein mesosome synthetic method.In view of this, the present invention provides a kind of synthesis key
The preparation method of intermediate.
The content of the invention
It is an object of the invention to provide a kind of taxanes intermediate compound I, the synthetic method of II, the reaction conditions of this method
Mildly, at low cost and environmentally friendly, obtained taxanes intermediate can be used as chiral side chain to be used for taxone
Synthesis.
In order to realize the above-mentioned purpose of the present invention, spy uses following technical scheme：
A kind of synthetic method of taxanes intermediate compound I, the structural formula of taxanes intermediate compound I are
The synthetic method includes：Under protective gas atmosphere, make (3R, 4S) -1- (4- anisyls) -3- hydroxy-4-phenyls -
With 1,5- double (halogenated diisopropyl silylation) pentanes nucleophilic substitution occurs for 2- aza cyclo-butanones.
Further, in preferred embodiments of the present invention, 1,5- double (halogenated diisopropyl silylation) pentanes are double for 1,5-
(chloro diisopropyl silylation) pentane.
Further, in preferred embodiments of the present invention, nucleophilic substitution be in the presence of nucleophilic catalyst into
Capable.
Further, in preferred embodiments of the present invention, nucleophilic catalyst includes 4-dimethylaminopyridine or 4- tetrahydrochysenes
Pyrroles's yl pyridines.
Further, in preferred embodiments of the present invention, the reaction dissolvent of nucleophilic substitution is ether solvent.
Further, in preferred embodiments of the present invention, ether solvent includes tetrahydrofuran, ether, methyl ether and epoxy
At least one of ethane.
Further, in preferred embodiments of the present invention, the reaction temperature of nucleophilic substitution is -5~10 DEG C.
Further, in preferred embodiments of the present invention, protection gas is nitrogen or inert gas.
A kind of synthetic method of taxanes intermediate II, the structural formula of taxanes intermediate II are
Synthetic method includes：By taxanes intermediate compound I nitre made from the synthetic method of any one of claim 1~6
Sour cerium ammonium takes off PMB protecting groups, obtains compound III, and structural formula isIt will
Compound III carries out amido protecting reaction with dimethyl dicarbonate butyl ester.
Further, in preferred embodiments of the present invention, in the reaction that PMB protecting groups are taken off with ammonium ceric nitrate, reaction is molten
Agent is acetone or acetonitrile.
Further, in preferred embodiments of the present invention, in the reaction that PMB protecting groups are taken off with ammonium ceric nitrate, reaction temperature
It spends for -5~10 DEG C.
Further, in preferred embodiments of the present invention, the reaction temperature of amido protecting reaction is 20~30 DEG C, reaction
Solvent is tetrahydrofuran or dichloromethane.
Compared with prior art, beneficial effects of the present invention for example including：
This taxanes intermediate compound I provided by the invention, the synthetic method of II, with (3R, 4S) -1- (4- methoxy benzene
Base) -3- hydroxy-4-phenyl -2- aza cyclo-butanones be raw material, reacted with chlorosilane, reaction condition is mild, at low cost, and
Environmentally friendly, the ee values of obtained taxanes intermediate compound I and II are high, purity is big, high income, chiral side chain can be used as to use
In the synthesis of taxone, the manufacturing cost of taxone can be effectively reduced.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person, the condition suggested according to normal condition or manufacturer carry out.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
The feature and performance of the present invention are described in further detail with reference to embodiments：
A kind of synthetic method of taxanes intermediate compound I of first embodiment
Embodiment 1
The present embodiment provides a kind of synthetic methods of taxanes intermediate compound I：
Under nitrogen protection, (3R, 4S) -1- (4- anisyls) -3- hydroxy-4-phenyl -2- nitrogen is put into reaction bulb
Heterocycle butanone 11.2g, tetrahydrofuran 150g are cooled to 0-5 degree, add in 4-dimethylaminopyridine 10.1g, stirring, then to anti-
It answers and double (chloro diisopropyl silylation) the pentane 15.5g of 1,5- is added dropwise in system, finish, when reaction 2 is small, add in water 200g, stir,
Layering, organic phase drying concentration, obtains intermediate compound I, can directly carry out next step reaction without processing.HPLC purity 94.4%, ee
Value 100.0%.
Embodiment 2
The present embodiment provides a kind of synthetic methods of taxanes intermediate compound I：
Under nitrogen protection, (3R, 4S) -1- (4- anisyls) -3- hydroxy-4-phenyl -2- nitrogen is put into reaction bulb
Heterocycle butanone 22.91g, ether 200g are cooled to 0-5 degree, add in 20.67g4- nafoxidine yl pyridines, stirring, then to anti-
It answers and double (chloro diisopropyl silylation) the pentane 32g of 1,5- is added dropwise in system, finish, when reaction 1 is small, add in 400 grams of water, stir,
Layering, organic phase drying concentration, obtains intermediate compound I, can directly carry out next step reaction without processing.HPLC purity 95.4%, ee
Value 99.8%.
Embodiment 3
The present embodiment provides a kind of synthetic methods of taxanes intermediate compound I：
Under argon gas gas shielded, (3R, 4S) -1- (4- anisyls) -3- hydroxy-4-phenyls -2- is put into reaction bulb
Aza cyclo-butanone 22.91g, ethylene oxide 200g are cooled to -5~5 DEG C, add in 20.67g 4- nafoxidine yl pyridines, stir,
Then double (chloro diisopropyl silylation) the pentane 32g of 1,5- are added dropwise into reaction system, finish, when reaction 1 is small, add in water 400
Gram, it stirs, layering, organic phase drying concentration obtains intermediate compound I, can directly carry out next step reaction without processing.HPLC purity
95.0%, ee value 99.9%.
A kind of synthetic method of taxanes intermediate II of second embodiment
Embodiment 4
The present embodiment provides a kind of synthetic method of taxanes intermediate II, including：
Step a：Using intermediate compound I made from embodiment 1 as raw material, intermediate compound I 10g is taken, adds 150g acetone solutions, is cooled down
To 0-5 degree, 25% ammonium ceric nitrate aqueous solution 200g is added dropwise, after the completion of reaction, the 200g that adds methylene chloride layerings, saturation sulfurous acid
Sodium solution washs organic layer, anhydrous sodium sulfate drying, and filtering is concentrated to give compound III.
Step b：Compound III20g is added in reaction bulb, tetrahydrofuran 300g dissolvings is then added in, stirs 30 minutes
(system is in rufous clear liquid), 20~30 DEG C of addition dimethylamino naphthyridine 2g of control temperature, is cooled to 0~5 DEG C.Then to reaction
Di-tert-butyl dicarbonate 24g is added in system, after completion of the reaction, adds water washing, anhydrous sodium sulfate drying is concentrated to give intermediate
II.3 step total recoverys 65.9%, HPLC contents 94.8%, HPLC purity 97.9%, ee values 99.8%.Nuclear magnetic data：1H NMR
(acetone-d6,600MHz), 7.36 (o of б；4H, Ph-3m)；7.30(o；4H, Ph-3o)；7.30(t；2H, Ph-3p)；5.29(d；
2H, H2)；5.15(d；2H, H3)；1.35(s；18H, C-O-Me3)；0.86-0.80(o.d；24H, Me2)；0.64(septet；
2H, Si-CH)；-0.18(s；2H, Si-CH2-Si).
Embodiment 5
The present embodiment provides a kind of synthetic method of taxanes intermediate II, including：
Step a：Using intermediate compound I made from embodiment 1 as raw material, intermediate compound I 20g is taken, 200g acetonitriles is added to dissolve, cooling
To 0-5 degree, 25% ammonium ceric nitrate aqueous solution 300g is added dropwise, after the completion of reaction, the 400g that adds methylene chloride layerings, saturation sulfurous acid
Sodium solution washs organic layer, anhydrous sodium sulfate drying, and filtering is concentrated to give compound III.
Step b：Compound III50g is added in reaction bulb, dichloromethane 200g dissolvings is then added in, stirs 30 minutes
(system is in rufous clear liquid), 20~30 DEG C of addition dimethylamino naphthyridine 6g of control temperature, is cooled to 0~5 DEG C.Then to reaction
Di-tert-butyl dicarbonate 75g is added in system, after completion of the reaction, adds water washing, anhydrous sodium sulfate drying is concentrated to give intermediate
II.3 step total recoverys 62.4%, HPLC contents 96.1%, HPLC purity 98.5%, ee values 99.9%.
It is to sum up shown, present embodiment provide this taxanes intermediate compound I, the synthetic method of II, with (3R, 4S)-
1- (4- anisyls) -3- hydroxy-4-phenyl -2- aza cyclo-butanones are raw material, are reacted with chlorosilane, reaction condition temperature
With at low cost and environmentally friendly, the ee values of obtained taxanes intermediate compound I and II are high, purity is big, high income, Ke Yizuo
The synthesis of taxone is used for for chiral side chain, the manufacturing cost of taxone can be effectively reduced.
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from the present invention's
Many other change and modification can be made in the case of spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of synthetic method of taxanes intermediate compound I, which is characterized in that the structural formula of the taxanes intermediate compound I is
The synthetic method includes：Under protective gas atmosphere, make (3R, 4S) -1- (4- anisyls) -3- hydroxy-4-phenyls -2-
With 1,5- double (halogenated diisopropyl silylation) pentanes nucleophilic substitution occurs for aza cyclo-butanone.
2. the synthetic method of taxanes intermediate compound I according to claim 1, which is characterized in that the nucleophilic displacement of fluorine is anti-
It should be carried out in the presence of nucleophilic catalyst.
3. the synthetic method of taxanes intermediate compound I according to claim 2, which is characterized in that the nucleophilic catalyst
Including 4-dimethylaminopyridine or 4- nafoxidine yl pyridines.
4. the synthetic method of taxanes intermediate compound I according to claim 1, which is characterized in that the nucleophilic displacement of fluorine is anti-
The reaction dissolvent answered is ether solvent.
5. the synthetic method of taxanes intermediate compound I according to claim 4, which is characterized in that the ether solvent bag
Include at least one of tetrahydrofuran, ether, methyl ether and ethylene oxide.
6. the synthetic method of taxanes intermediate compound I according to claim 1, which is characterized in that the nucleophilic displacement of fluorine is anti-
The reaction temperature answered is -5~10 DEG C.
A kind of 7. synthetic method of taxanes intermediate II, which is characterized in that the structural formula of the taxanes intermediate II
For
The synthetic method includes：By taxanes intermediate compound I made from claim 1~6 any one of them synthetic method
PMB protecting groups are taken off with ammonium ceric nitrate, obtain compound III, structural formula is
The compound III and dimethyl dicarbonate butyl ester are subjected to amido protecting reaction.
8. the synthetic method of taxanes intermediate II according to claim 7, which is characterized in that take off institute with ammonium ceric nitrate
In the reaction for stating PMB protecting groups, reaction dissolvent is acetone or acetonitrile.
9. the synthetic method of taxanes intermediate II according to claim 7, which is characterized in that take off institute with ammonium ceric nitrate
In the reaction for stating PMB protecting groups, reaction temperature is -5~10 DEG C.
10. the synthetic method of taxanes intermediate II according to claim 7, which is characterized in that the amido protecting
The reaction temperature of reaction is 20~30 DEG C, and reaction dissolvent is tetrahydrofuran or dichloromethane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810079487.5A CN108069999A (en) | 2018-01-26 | 2018-01-26 | A kind of synthetic method of taxanes intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810079487.5A CN108069999A (en) | 2018-01-26 | 2018-01-26 | A kind of synthetic method of taxanes intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108069999A true CN108069999A (en) | 2018-05-25 |
Family
ID=62157130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810079487.5A Withdrawn CN108069999A (en) | 2018-01-26 | 2018-01-26 | A kind of synthetic method of taxanes intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108069999A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007051306A1 (en) * | 2005-11-04 | 2007-05-10 | Bioxel Pharma Inc. | New methods for the preparation of taxanes using chiral auxiliaries |
| CN101863861A (en) * | 2009-04-16 | 2010-10-20 | 山东靶点药物研究有限公司 | Simple and efficient method for preparing paclitaxel analogue Larotaxel |
| WO2014072996A2 (en) * | 2012-11-09 | 2014-05-15 | Intas Pharmaceuticals Limited | Process for the preparation of cabazitaxel and its intermediates |
-
2018
- 2018-01-26 CN CN201810079487.5A patent/CN108069999A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007051306A1 (en) * | 2005-11-04 | 2007-05-10 | Bioxel Pharma Inc. | New methods for the preparation of taxanes using chiral auxiliaries |
| CN101863861A (en) * | 2009-04-16 | 2010-10-20 | 山东靶点药物研究有限公司 | Simple and efficient method for preparing paclitaxel analogue Larotaxel |
| WO2014072996A2 (en) * | 2012-11-09 | 2014-05-15 | Intas Pharmaceuticals Limited | Process for the preparation of cabazitaxel and its intermediates |
Non-Patent Citations (3)
| Title |
|---|
| HAIBO GE等: "Synthesis of docetaxel and butitaxel analogues through kinetic resolution of racemic β-lactams with 7-O-triethylsilylbaccatinⅢ", 《J. ORG. CHEM.》 * |
| THOTA GANESH等: "Evaluation of the Tubulin-Bound Paclitaxel Conformation: Synthesis, Biology, and SAR Studies of C-4 to C-3¢ Bridged Paclitaxel Analogues", 《J. MED. CHEM.》 * |
| 阎家麒: "紫杉醇手性侧链合成与紫杉醇半合成", 《精细与专用化学品》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Commercon et al. | Improved protection and esterification of a precursor of the taxotere® and taxol side chains | |
| TW410228B (en) | Phosphonooxymethyl ethers of taxane derivatives | |
| Zarrelli et al. | New C-23 modified of silybin and 2, 3-dehydrosilybin: Synthesis and preliminary evaluation of antioxidant properties | |
| JPH11500141A (en) | Novel taxoids, their preparation and pharmaceutical compositions containing them | |
| JPS6330479A (en) | Taxol derivatives, manufacture and pharmaceutical composition | |
| CN103814018A (en) | Crystalline forms of cabazitaxel | |
| CN102993137B (en) | Method for industrial semi-synthetic docetaxel | |
| Xue et al. | Synthesis of Taxol and Docetaxel by Using 10‐Deacetyl‐7‐xylosyltaxanes | |
| CN112250647A (en) | Taxane prodrug, preparation method and application | |
| Wei et al. | Synthesis, characterization and antitumor activity of novel ferrocene-coumarin conjugates | |
| CN114380864B (en) | Dihydroartemisinin derivative, preparation method, pharmaceutical composition and application thereof in preparation of antitumor drugs | |
| CN101838284A (en) | Dibutyltin oxide coordination compound and preparation method and application thereof | |
| CN108069999A (en) | A kind of synthetic method of taxanes intermediate | |
| CN110305118A (en) | A kind of synthetic method that suitable industrial production En Gelie is net | |
| Alizadeh et al. | Synthesis, characterization, crystal structure determination, and luminescence properties of two new gold (III) complexes with phenanthridine ligand | |
| AU784830B2 (en) | Synthesis of water soluble 9-dihydro-paclitaxel derivatives from 9-dihydro-13-acetylbaccatin III | |
| CN103012329A (en) | Preparation method of taxol anticancer drugs Cabazitaxel XRP6258 | |
| CN113402565B (en) | Tetravalent platinum complex containing posaconazole, preparation method and application thereof | |
| CN112175014B (en) | Nitric oxide donor type tetravalent platinum derivative, preparation method and medical application thereof | |
| CN113549122B (en) | Glycosylated tetravalent platinum compound targeting GLUTs, synthetic method and application thereof | |
| CN101851251B (en) | Dibutyltin (IV) complex for acyl hydrazone Schiff-base ligand and preparation method and application thereof | |
| CN103254187A (en) | Preparation method of new taxane derivative | |
| KR100345047B1 (en) | Novel taxaneterpine compounds | |
| CN102675256A (en) | Synthetic method for cabazitaxel | |
| CN103012328B (en) | Method for preparing second-generation taxol anticancer drug Cabazitaxel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180525 |
|
| WW01 | Invention patent application withdrawn after publication |