CN101143858B - Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes - Google Patents

Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes Download PDF

Info

Publication number
CN101143858B
CN101143858B CN200610047743A CN200610047743A CN101143858B CN 101143858 B CN101143858 B CN 101143858B CN 200610047743 A CN200610047743 A CN 200610047743A CN 200610047743 A CN200610047743 A CN 200610047743A CN 101143858 B CN101143858 B CN 101143858B
Authority
CN
China
Prior art keywords
taxol
reaction
acetyl
trifluoromethanesulfonic acid
hydroxyl
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.)
Active
Application number
CN200610047743A
Other languages
Chinese (zh)
Other versions
CN101143858A (en
Inventor
杨凌
张延延
葛广波
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.)
Zhangjiagang Institute Of Industrial Technology Dalian Institute Of Chemical Physics China Academy Of Sciences
Original Assignee
Dalian Institute of Chemical Physics of CAS
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.)
Filing date
Publication date
Application filed by Dalian Institute of Chemical Physics of CAS filed Critical Dalian Institute of Chemical Physics of CAS
Priority to CN200610047743A priority Critical patent/CN101143858B/en
Publication of CN101143858A publication Critical patent/CN101143858A/en
Application granted granted Critical
Publication of CN101143858B publication Critical patent/CN101143858B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Epoxy Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The invention relates to a preparation method of paclitaxel and other taxanes. By using trifluoromethanesulfonic salt as catalyst, the method is realized by selectively acylating the hydroxyls at C (10) and C (2') of a 10-deacetyl-taxane compound. The produced taxane with acylated hydroxyls at C (10) and C (2') can be used as an important intermidiate for preparing the paclitaxel and other taxanes.

Description

The method of a kind of selectively acylating taxone C (10) and C (2') position hydroxyl
Technical field:
The present invention relates to the preparation method of a kind of taxol and other Taxan; relate in particular under the catalytic condition of fluoroform sulphonate; go acetyl-bearing taxanes to be converted into the Taxan of C (10) and C (2 ') position acylated hydroxy 10-by a step selectively acylating reaction, and the latter can be used as the important intermediate for preparing taxol and analogue thereof.
Background technology:
Taxol (Paclitaxel, formula II, 1) and Docetaxel (Docetaxel) currently are widely used in the different sorts tumor treatment as a clinical line medication.
Figure G200610047743XD00011
1.R=Ac taxol (Paclitaxel) 3.10-removes acetyl-baccatin III
2.R=H 10-removes acetyl-taxol
Formula II taxol, 10-go acetyl-taxol and 10-to remove acetyl-baccatin III
Extract culture plant cell, biosynthesizing by Chinese yew genus plants, means such as fungi fermentation and chemistry are semi-synthetic can obtain a large amount of 10-and remove acetyl-bearing taxanes, remove acetyl-taxol (formula II, 2) as 10-, 10-removes acetyl-baccatin III (10-DAB, formula II, 3) etc.Can obtain taxol (Taxol) or other bearing taxanes of high antitumour activity by the hydroxyl of acidylate C (10) position.Acidylate work at such Taxan at present mainly concentrates on following two aspects:
(1) adopt acid binding agent catalytie esterification 10-to remove acetyl-taxol (alkane)
People such as Rao (J.Heterocycl.Chem., 1997,34, pp.675) utilize periodate oxidation cracking C (7) position xylosyl, pyridine as the condition of acid binding agent under after the glycoloylization with C (10) and C (2 ') position, slough residual group on C (7) position with phenylhydrazine again, thereby obtain the acetylizad taxol in C (2 ') position, use dimethylamine selective hydrolysis C (2 ') position ethanoyl promptly to obtain taxol (US5200534; US5367086).
People such as Sisti (US5914411) go the acetyl baccatin III to be dissolved in the THF reaction system 10-, and the hydroxyl to wherein adding lithium salts activation C (10) position adds TEA again and makes acid binding agent, and Acetyl Chloride 98Min. has optionally obtained baccatin III as acylating agent.Its subsequently patent (US6048990, US6066749) in, they expand to this method after C (2 ') position hydroxyl is protected, highly selective acylation C (10) position hydroxyl obtains the protected taxol of C (2 ') position hydroxyl.
People such as Chattopadhyay (US5856532) will obtain 10-and remove the acetyl taxane compounds; after silicon ether is protected the hydroxyl of its C (7) and C (2 ') position; acetylize C (10) position hydroxyl under the condition that pyridine exists again, last desiliconization ether protecting group obtains target product.
People such as Fang (chemical wall bulletin; 8 (10); 1997; pp.847) find that 7-table-10-goes C in acetyl-taxol (7) hydroxyl at pyridine, is difficult to be acetylation under the condition of Acetyl Chloride 98Min.. therefore, they protect C (2 with chlorotriethyl silane;) the position hydroxyl; acetylize C (10) position hydroxyl under pyridine catalysis, slough C (2 ') position silicon ether protecting group after, obtain 7-table-taxol.
(2) adopt Lewis acid catalysis acidylate 10-to remove acetyl-taxol (alkane)
People such as Holton (Tetrahedron Letters; 1998,39, pp.2883) find; Lewis acid is being arranged; as cerous compounds, zinc chloride is under the situation that tin chloride etc. exist; taxol after going acetyl baccatin III or C (2 ') position hydroxyl protected for 10-; the hydroxyl that the hydroxyl of C (10) position can have precedence over C (7) position by the selectivity acidylate (CN125196C, WO1999/009021, US6706896).But in its research work, do not relate to that to have the Taxan of free hydroxyl with C (2 ') position be raw material, the problem of acidylate C (2 ') position hydroxyl.
People such as Damen (Tetrahedron Letters, 1998,39, pp.6081) find, under the fluoroform sulphonate catalysis of rare earth element, adopt diacetyl oxide can with 10-DAB optionally acetyl turn to baccatin III.If adopt other acid anhydrides, by C (10) the position hydroxyl of selectively acylating 10-DAB, can obtain different derivatives (EP0875508, US5874595, JP10298171).Yet in its research work, do not relate to the Taxan that there is side chain in C (13) position, do not relate to C under this reaction conditions (1) yet, C (7), C (10), the selectively acylating problem between each hydroxyl of C (2 ') position.
People such as Tang Dingning (CN1640871A; WO2005/073209) find in reaction system, to contain rare earth chloride; rare earth hydrate; the oxychlorination rare earth; or during the double sulphate of rare earth element; can adopt diacetyl oxide to come highly selective acylation 10-to remove acetyl-taxol C (10) and C (2 ') position hydroxyl, slough C (2 ') position ethanoyl again and can obtain taxol.
The fluoroform sulphonate of IIIB family metallic element is the novel acylation reaction catalyst of developing in recent years of a class (Yamamoto et al., J.Am.Chem.Soc., 1995,117,4413).For in C (1), C (7), C (10), there is the Taxan of a plurality of hydroxyls in C (2 ') position, investigates its catalytic activity to each acylated hydroxy reaction and is still a job that needs to be resolved hurrily.
Technology contents:
The object of the present invention is to provide and a kind ofly go the acetyl bearing taxanes to be converted into the taxol of C (10) and C (2 ') position acylated hydroxy or the preparation method of other Taxan 10-.The invention particularly relates to Taxan in C (1), C (10) and C (2 ') all contain hydroxyl in the position, and C (7) position can contain in the time of also can not containing free hydroxyl, use acylating agent optionally with C (10) and C (2 ') hydroxyl reaction.
Concrete enforcement of the present invention be by with the fluoroform sulphonate of IIIB family metallic element as catalyzer; in inert organic solvents, go acetyl-taxol (alkane) raw material to mix with 10-; under the condition of acid anhydrides as acylating agent; these catalyzer can optionally activate C (10) and C (2 ') position hydroxyl, thereby make C (10) and C (2 ') position hydroxyl prior to C (1) and hydroxyl position, C (7) position acidylate.Simultaneously, protected or when being replaced when C (1) and C (7) position hydroxyl by other group, adopt method of the present invention, also can obtain the Taxan of C (10) and C (2 ') acylated hydroxy.And the latter can obtain taxol or other Taxan by selective hydrolysis C (2 ') position acyl group under the alkaline condition.
This selectively acylating reaction is preferably carried out in ether solvent, as tetrahydrofuran (THF), and ether etc.But at methylene dichloride, chloroform, reaction also can take place in the good solvent of Taxans such as ethyl acetate, and just the reaction times slightly prolongs.This reaction system is preferably the solvent that strictness dewaters, and when the moisture in the system surpasses when a certain amount of, can reduce speed of response, even cause reaction to carry out.
This selectively acylating reacts the catalyzer that is adopted, and comes from the fluoroform sulphonate of IIIB family metallic element in the periodic table of elements.Preferably from the trifluoromethanesulfonic acid scandium, Ytterbiumtriflate, trifluoromethanesulfonic acid erbium, trifluoromethanesulfonic acid lanthanum, trifluoromethanesulfonic acid rubidium, trifluoromethanesulfonic acid samarium, trifluoromethanesulfonic acid dysprosium.
The reaction of this selectively acylating at room temperature can be carried out smoothly, helps reaction and reaches balance as early as possible but suitably heat up, and general preferably carries out at-80 ℃ to 100 ℃.
Described 10-goes acetyl-Taxan to have the structure of following general formula I
Figure G200610047743XD00041
Formula I
Wherein R1 is-H ,-OR ,-OSi (R) 3 or-COR; R2 and R3 can be the same or different, and are-H ,-R or-OR; Wherein R is H, the straight chain of C1 to C20, side chain or ring-like alkyl, and aryl, aralkyl, and the substituent of above-mentioned three kinds of alkyl, substituting group comprises hydroxyl, the alkoxyl group of C1 to C8, acetal, ketal, halogen, nitro and amino.
Especially, acetal as referred to herein and ketal partly have general structure
Figure G200610047743XD00042
X1 wherein; X2; X3; X4 acute pyogenic infection of finger tip hydrogen or alkyl, and alkyl can replace by any substituting group defined herein, and this part can comprise from carbohydrate or replace acetal or the ketal (KoppakaV.Rao that carbohydrate such as glucose or wood sugar are made; J.Heterocyclic Chem.34; 676 (1997)), when the protecting group that is used as C (7) position hydroxyl when this part enters in the Taxan of the present invention, X1 or X2 acute pyogenic infection of finger tip Taxan part.
The acylating agent that can be used for this selectively acylating reaction comprises various acid anhydrides, for example, diacetyl oxide, sym-dichloroacetic anhydride, trifluoroacetic anhydride, benzoyl oxide etc., the structure of described acid anhydrides has general structure
Figure G200610047743XD00051
Wherein R ' is straight chain, side chain or the ring-like alkyl of C1 to C20, aryl, and the halides of above-mentioned three kinds of alkyl.
Technical process of the present invention and chemical reaction general formula are shown in formula III.
Figure G200610047743XD00052
R1 wherein, R2, R3, R ' definition is the same.
Formula III
Taxan raw material involved in the present invention can be natural product source in C (10), the 10-that C (2 ') contains the position hydroxyl simultaneously removes acetyl-bearing taxanes monomer or its mixture.Simultaneously, via biosynthesizing, the Taxan that contains hydroxyl in above-mentioned position that the semi-synthetic or complete synthesis means of chemistry obtain also can adopt the present invention that C (10) and C (2 ') position hydroxyl are carried out selectively acylating.
Description of drawings:
Fig. 1 removes the LC-MS spectrogram of acetyl-taxol for 10-, and 10-removes the negative ion signal of acetyl-taxol: [M-H] -At m/z 810.4;
Fig. 2 is the LC-MS spectrogram of 2 '-ethanoyl-taxol, the negative ion signal of 2 '-ethanoyl-taxol: [M-H] -At m/z 894.9;
Fig. 3 is the LC-MS spectrogram of taxol, the negative ion signal of taxol: [M-H] -At m/z 852.3;
Fig. 4 removes the LC-MS spectrogram of acetyl-Cephalomannine for 10-, and 10-removes the negative ion signal of acetyl-Cephalomannine: [M-H] -At m/z788.3;
Fig. 5 is the LC-MS spectrogram of Cephalomannine, the negative ion signal of Cephalomannine: [M-H] -Atm/z830.4;
Fig. 6 removes the LC-MS spectrogram of acetyl-7-wood sugar-taxol for 10-; 10-removes the negative ion signal of acetyl-7-wood sugar-taxol: [M-H] -At m/z 942.5.
Embodiment:
The following example is in order to further specify the present invention, rather than will limit its scope.
Embodiment 1 adopts multiple fluoroform sulphonate catalytie esterification 10-to go acetyl-taxol to produce 2 '-ethanoyl-taxol
Take by weighing 10-and remove acetyl-taxol (content 90%, the LC-MS spectrogram is seen Fig. 1) sample be dissolved in the reaction solvent, the fluoroform sulphonate that adds the normal IIIB of catalysis family metallic element, behind the thorough mixing, slowly drip about 3 normal diacetyl oxides, stir under the room temperature, after the TLC detection reaction is complete, adds saturated NaHCO3 solution and extinguish reaction.Reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam 2 '-ethanoyl-taxol (the LC-MS spectrogram is seen Fig. 2).The various catalyzer that adopted, catalytic amount, reaction solvent, reaction times and yield see Table 1.
Many kinds of fluoroform sulphonate catalytie esterifications of table 1 10-removes acetyl-taxol
Figure G200610047743XD00071
Embodiment 2 goes acetyl-taxol to produce taxol from 10-
Take by weighing 10-and remove acetyl-taxol (content 77%, the LC-MS spectrogram is seen Fig. 1) sample 1g, be dissolved in the 20ml tetrahydrofuran (THF), after adding 0.07g Ytterbiumtriflate thorough mixing, slowly drip the 0.35ml diacetyl oxide, reaction is 1.5 hours under the room temperature, add saturated NaHCO3 solution 25ml and extinguish reaction. reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 1.05g white solid. it is dissolved in the dimethylamine methanol solution of 50ml0.1%, after reacting 1h under the room temperature, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.95g white solid. this material behind silica gel column chromatography 0.61g taxol (content 90%, yield 67.8%, the LC-MS spectrogram is seen Fig. 3).
Embodiment 3 goes acetyl-Cephalomannine to produce Cephalomannine from 10-
Take by weighing 10-and remove acetyl-Cephalomannine (content 85%, the LC-MS spectrogram is seen Fig. 4) sample 1g, be dissolved in the 20ml tetrahydrofuran (THF), after adding 0.08g Ytterbiumtriflate thorough mixing, slowly drip the 0.35ml diacetyl oxide, reaction is 1.5 hours under the room temperature, adds saturated NaHCO3 solution 25ml and extinguishes reaction.Reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 0.93g white solid.It is dissolved in the dimethylamine methanol solution of 50ml0.1%, under the room temperature reaction 1h after, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.86g white solid.This material obtains 0.77g Cephalomannine (the LC-MS spectrogram is seen Fig. 5 for content 90%, yield 77.4%) behind silica gel column chromatography.
Embodiment 4 goes acetyl-7-wood sugar-taxol to produce taxol from 10-
Take by weighing 10-and remove the sample 1g of acetyl-7-wood sugar-taxol (content 90%, the LC-MS spectrogram is seen Fig. 6), be dissolved in the 50ml methanol (4: 1), add 0.9g sodium periodate and 3ml0.5M sulfuric acid after, reaction is 5 hours under the room temperature.Add 50ml water and extinguish reaction, reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 0.98g white solid.It is dissolved in the 20ml tetrahydrofuran (THF), behind the adding 0.08g Ytterbiumtriflate, slowly drips the 0.3ml diacetyl oxide, reaction is 1 hour under the room temperature, adds saturated NaHCO3 solution 25ml and extinguishes reaction, the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 1.03g white solid.It is dissolved in the 20ml methanol (4: 1), adds 3ml acetate and 0.5ml phenylhydrazine, 50 ℃ down reaction add 50ml water and extinguish reaction after 3 hours, the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.95g white solid.It is dissolved in the dimethylamine methanol solution of 50ml0.1%, under the room temperature reaction 1h after, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.92g white solid.This material obtains 0.53g taxol (the LC-MS spectrogram is seen Fig. 3 for content 90%, yield 58.6%) behind silica gel column chromatography.
Embodiment 5 goes acetyl-taxol to produce 10-benzoyl-10-from 10-and removes the acetyl taxol
Take by weighing 10-and remove the sample 1g of acetyl taxol (content 77%, the LC-MS spectrogram is seen Fig. 1), be dissolved in the 20ml tetrahydrofuran (THF), 0.08g behind the Ytterbiumtriflate thorough mixing, add the 0.5g benzoyl oxide, 50 ℃ were reacted 3 hours down, add saturated NaHCO3 solution 25ml and extinguish reaction.Reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 0.91g white solid.It is dissolved in the dimethylamine methanol solution of 50ml0.1%, under the room temperature reaction 1h after, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.87g white solid.This material obtains 0.72g 10-benzoyl-10-and removes acetyl taxol (content 85%, yield 69.3%) behind silica gel column chromatography.
Embodiment 6 goes acetyl-7-O-Troc-taxol to produce 10-trifluoroacetyl-10-from 10-and removes acetyl-7-O-Troc-taxol
Take by weighing 10-and remove the sample 0.5g of acetyl-7-O-Troc-taxol (content 78%), be dissolved in the 10ml tetrahydrofuran (THF), add 0.03g trifluoromethanesulfonic acid lanthanum thorough mixing after, add the 0.3g trifluoroacetic anhydride, 20 ℃ of reactions 0 down.5 hours, add saturated NaHCO3 solution 15ml and extinguish reaction.Reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 0.52g white solid.This material is dissolved in the dimethylamine methanol solution of 25ml0.1%, under the room temperature reaction 1h after, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.49g white solid.This material obtains 0.37g10-trifluoroacetyl-10-and removes acetyl-7-O-Troc-taxol (content 85%, yield 74.4%) behind silica gel column chromatography.
Embodiment 7 goes acetyl-7-O-TES-taxol to produce 10-propionyl-10-from 10-and removes acetyl-7-O-TES-taxol
Take by weighing 10-and remove the sample 0.5g of acetyl-7-O-TES-taxol (content 80%), be dissolved in the 10ml tetrahydrofuran (THF), add 0.03g trifluoromethanesulfonic acid scandium, behind the thorough mixing, add the 1.0ml propionic anhydride, 30 ℃ were reacted 1.5 hours down, add saturated NaHCO3 solution 15ml and extinguish reaction. reaction back feed liquid ethyl acetate extraction, anhydrous sodium sulfate drying, vacuum revolve steam the 0.57g white solid. this material is dissolved in the dimethylamine methanol solution of 25ml0.1%, after reacting 1h under the room temperature, use the ethyl acetate extraction feed liquid, anhydrous sodium sulfate drying, vacuum revolve steam the 0.52g white solid. this material obtains 0.38g10-propionyl-10-and removes acetyl-7-O-TES-taxol (content 80%, yield 71.5%) behind silica gel column chromatography.

Claims (5)

  1. A selectively acylating taxone C (10) and C (2 ') position hydroxyl method, it is characterized in that:
    ---the fluoroform sulphonate that contains the normal IIIB of catalysis family metallic element in the reaction system is as catalyzer;
    ---use to be no less than 2 moles of normal acid anhydrides of substrate as acylating agent, the 10-that processing has following general structure (formula I) removes acetyl-bearing taxanes, thereby obtains the Taxan of C (10) and C (2 ') position acidylate;
    Formula I
    Wherein R1 is-H ,-OR ,-OSi (R) 3 or-OCOR; R2 is identical with R3 or different, is-H ,-R or-OR; Described R is H, the straight chain of C1 to C20, side chain or ring-like alkyl, and aryl, aralkyl, the substituent of perhaps above-mentioned three kinds of alkyl, substituting group comprises hydroxyl, the alkoxyl group of C1 to C8, acetal, ketal, halogen, nitro or amino;
    ---reaction process is carried out in inert organic solvents.
  2. 2. according to the method for the described selectively acylating taxone C of claim 1 (10) and C (2 ') position hydroxyl; it is characterized in that: described catalyzer is selected from the trifluoromethanesulfonic acid scandium; Ytterbiumtriflate; the trifluoromethanesulfonic acid erbium; the trifluoromethanesulfonic acid lanthanum; the trifluoromethanesulfonic acid rubidium, trifluoromethanesulfonic acid samarium, trifluoromethanesulfonic acid dysprosium.
  3. 3. according to the method for described selectively acylating taxone C of claim 1 (10) and C (2 ') position hydroxyl, it is characterized in that: the structure of described acid anhydrides has general structure
    Figure F200610047743XC00012
    Wherein R ' is straight chain, side chain or the ring-like alkyl of C1 to C20, aryl, and the halides of above-mentioned three kinds of alkyl.
  4. 4. according to the method for described selectively acylating taxone C of claim 1 (10) and C (2 ') position hydroxyl, it is characterized in that: described inert organic solvents is selected from tetrahydrofuran (THF), ether; ethyl acetate; dioxane, chloroform, the mixed system of one or more in the methylene dichloride.
  5. 5. according to the method for described selectively acylating taxone C of claim 1 (10) and C (2 ') position hydroxyl, it is characterized in that: described temperature of reaction is-80 ℃ to 100 ℃.
CN200610047743A 2006-09-15 2006-09-15 Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes Active CN101143858B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN200610047743A CN101143858B (en) 2006-09-15 2006-09-15 Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN200610047743A CN101143858B (en) 2006-09-15 2006-09-15 Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes

Publications (2)

Publication Number Publication Date
CN101143858A CN101143858A (en) 2008-03-19
CN101143858B true CN101143858B (en) 2010-05-12

Family

ID=39206612

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200610047743A Active CN101143858B (en) 2006-09-15 2006-09-15 Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes

Country Status (1)

Country Link
CN (1) CN101143858B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111848623B (en) * 2019-04-25 2021-11-12 中国科学院大连化学物理研究所 Method for synthesizing fluorine-containing chiral ketal amine by catalysis of chiral phosphoric acid

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5874595A (en) * 1997-05-02 1999-02-23 Pharmachemie B.V. Method for the preparation of baccatin III and derivatives thereof from 10-deacetylbaccatin III
CN1640817A (en) * 2004-01-13 2005-07-20 中国科学院过程工程研究所 Method for preparing zirconium phosphate

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5874595A (en) * 1997-05-02 1999-02-23 Pharmachemie B.V. Method for the preparation of baccatin III and derivatives thereof from 10-deacetylbaccatin III
CN1640817A (en) * 2004-01-13 2005-07-20 中国科学院过程工程研究所 Method for preparing zirconium phosphate

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
.具有抗癌活性的水溶性紫杉醇前体药物的合成.国外医药.植物药分册7(1992) 6.1992,7(1992)(6),263.
Kazuaki Ishihara, Manabu Kubota, Hideki Kurihara, HisashiYamamoto.Scandium Trifluoromethanesulfonate as an Extremely ActiveAcylation Catalyst.Jounal of the American Chemical society117(1995) 15.1995,117(1995)(15),4413-4414.
Kazuaki Ishihara, Manabu Kubota, Hideki Kurihara, HisashiYamamoto.Scandium Trifluoromethanesulfonate as an Extremely ActiveAcylation Catalyst.Jounal of the American Chemical society117(1995) 15.1995,117(1995)(15),4413-4414. *
Valentino J S
Valentino J S;.具有抗癌活性的水溶性紫杉醇前体药物的合成.国外医药.植物药分册7(1992) 6.1992,7(1992)(6),263. *

Also Published As

Publication number Publication date
CN101143858A (en) 2008-03-19

Similar Documents

Publication Publication Date Title
US7906661B2 (en) Semi-synthetic conversion of paclitaxel to docetaxel
US8293930B1 (en) One pot synthesis of taxane derivatives and their conversion to paclitaxel and docetaxel
JP3295879B2 (en) Method for producing taxane derivative
CA2569498C (en) Semi-synthesis of taxane intermediates and their conversion to paclitaxel and docetaxel
CN101088994A (en) Process of synthesizing taxol and docetaxel
TW200906813A (en) Stable anhydrous crystalline docetaxel and method for the preparation thereof
US7893283B2 (en) Semi-synthesis of taxane intermediates and their conversion to paclitaxel and docetaxel
CN101143858B (en) Method for selectively acylating hydroxyl group at C(10) and C(2) position of taxanes
CA2205745C (en) Method for the preparation of baccatin iii and derivatives thereof from 10-deacetylbaccatin iii
CN101274924B (en) Preparation for paclitaxel and derivatives thereof
CN101274923B (en) Preparation for paclitaxel, baccatin III and derivates thereof
CN102180914A (en) Preparation method of 2-deoxidizing-D-glucose
CN101139329A (en) Method for selectively acylating taxone C(10) hydroxy
CN100349882C (en) Method for preparing derivatives of baccatin iii
CN103130753B (en) The semisynthesis of antitumor drug paclitaxel
CN102050804A (en) Methods for preparing docetaxel and intermediates thereof
CN101007795B (en) Paclitaxel and docetaxel synthesis method
CZ20031534A3 (en) Process for preparing paclitaxel
CN106632160A (en) Methods for preparing semi-synthetic paclitaxel and intermediate thereof
WO2008032104A1 (en) One pot synthesis of taxane derivatives and their conversion to paclitaxel and docetaxel
CN104250235B (en) A kind of preparation method of paclitaxel
CN111484538B (en) Preparation method of homoplantaginoside
CN108440552B (en) A kind of synthetic method of high activity macrolide Ivorenolide B
EP1298128B1 (en) Process for the preparation of 10-deacetylbaccatin III
CN101245033A (en) Isoserine ester derivant and method of preparing the same

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
ASS Succession or assignment of patent right

Owner name: ZHUHAI DAORONG BIOTECHNOLOGY CO., LTD.

Free format text: FORMER OWNER: DALIAN INSTITUTE OF CHEMICAL PHYSICS, CHINESE ACADEMY OF SCIENCES

Effective date: 20111130

C41 Transfer of patent application or patent right or utility model
COR Change of bibliographic data

Free format text: CORRECT: ADDRESS; FROM: 116023 DALIAN, LIAONING PROVINCE TO: 519040 ZHUHAI, GUANGDONG PROVINCE

TR01 Transfer of patent right

Effective date of registration: 20111130

Address after: Sanzao town Jinwan District Guangdong city Zhuhai province moon building 519040 floor 21B room 2

Patentee after: Zhuhai Daorong Biotechnology Co., Ltd.

Address before: 116023 Zhongshan Road, Liaoning, No. 457,

Patentee before: Dalian Institute of Chemical Physics, Chinese Academy of Sciences

C41 Transfer of patent application or patent right or utility model
TR01 Transfer of patent right

Effective date of registration: 20151203

Address after: 116023 Zhongshan Road, Liaoning, No. 457,

Patentee after: Dalian Institute of Chemical Physics, Chinese Academy of Sciences

Address before: Sanzao town Jinwan District Guangdong city Zhuhai province moon building 519040 floor 21B room 2

Patentee before: Zhuhai Daorong Biotechnology Co., Ltd.

TR01 Transfer of patent right

Effective date of registration: 20180228

Address after: 215600 A 207 room A building center of Zhangjiagang Free Trade Zone, Suzhou Free Trade Zone, Jiangsu

Patentee after: Zhangjiagang Institute of industrial technology, Dalian Institute of Chemical Physics, China Academy of Sciences

Address before: 116023 Zhongshan Road, Liaoning, No. 457,

Patentee before: Dalian Institute of Chemical Physics, Chinese Academy of Sciences

TR01 Transfer of patent right