- Semisynthesis method for docetaxel
-
The invention relates to a semisynthesis method for docetaxel. The semisynthesis method comprises the following steps: protecting hydroxyl groups on 7-carbon and 10-carbon on 10-DAB III by using chloroformic acid-2,2,2-trichloroethyl ester so as to obtain an intermediate I, performing a condensation reaction on the intermediate I and a five-membered ring side chain so as to obtain an intermediateII, performing ring opening on the intermediate II under the action of hydrochloric acid to remove a protecting group on the five-membered ring side chain so as to obtain an intermediate III, and removing a Troc protecting group from the intermediate III under an acidic condition so as to obtain the docetaxel. The semisynthesis method provided by the invention has the advantages of simple processroute, mild reaction conditions, fewer impurities generated in the reaction process, higher yield and stable properties of obtained intermediates, and applicability to industrial large-scale production.
- -
-
-
- Method for purifying docetaxel
-
The invention discloses a method for purifying docetaxel. A docetaxel solid precipitates from a dichloromethane and toluene mixed solution. The purifying method has the advantages of great reduction of the single content of every impurity in docetaxel, introduction of few impurities, improvement of the purity of the product, and high yield, and is very suitable for industrial large-scale production, and the obtained product meets preparation demands, and can be directly used to prepare a docetaxel injection.
- -
-
-
- Docetaxel side chain 2'-derived novel taxanes antitumor compound as well as synthesis method and application thereof
-
The invention discloses a docetaxel side chain 2'-derived novel taxanes antitumor compound shown as the general structure formula (I) as well as a synthesis method and application thereof. In the formula, X is N or O, R is H or acetyl, and R' is H, nitryl, cyano, methoxyl or a halogen group. The synthesis method takes 10-deacetylbaccatin is used as a raw material; after 7-OH and 10-OH are protected, condensation with phenylisoserine (side chain) protecting 3'-NHBoc and 2'-OH in the presence of condensation agents DCC (Dicyclohexylcarbodiimide) and DMAP (Dimethylaminopyridine) is performed; esterification with substituted phenyl isoxazole carboxylic acid or substituted phenyl oxadiazole methyl carboxylic acid in the presence of the DCC and the DMAP is performed; finally, a protecting group is removed to obtain the compound. The compound disclosed by the invention has relatively high activity on tumor cells.
- -
-
-
- METHOD FOR PREPARING TAXANE DERIVATIVES
-
Provided is a method for preparing a taxane derivative, comprising: carrying out condensation of a phenylisoserine derivatives having a protective group introduced thereto or a mixture of isomers thereof, as a side chain, with a baccatin III derivative or 10-deacetyl-baccatin III derivative to obtain a mixture of isomers; separating the isomers via chromatography; and carrying out a reversion of the stereochemical structure of a selectively separated isomer, which is suitable for producing a taxane derivative in a large scale with high yield.
- -
-
-
- METHOD FOR PREPARING TAXANE DERIVATIVES
-
Provided is a method for preparing a taxane derivative, comprising: carrying out condensation of a phenylisoserine derivatives having a protective group introduced thereto or a mixture of isomers thereof, as a side chain, with a baccatin III derivative or 10-deacetyl-baccatin III derivative to obtain a mixture of isomers; separating the isomers via chromatography; and carrying out a selective reversion of the stereochemical structure of a separated isomer, which is suitable for producing a taxane derivative in a large scale with high yield.
- -
-
Page/Page column 16
(2010/11/05)
-
- Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: Hemisynthesis of Taxotere through Ru-DIFLUORPHOS asymmetric hydrogenation
-
The dynamic kinetic resolution (DKR) of racemic α-chloro β-ketoesters and α-chloro β-ketophosphonates through ruthenium-mediated asymmetric hydrogenation is reported. The corresponding α-chloro β-hydroxyesters and α-chloro β- hydroxyphosphonates were obtained in good to high enantio- and diastereomeric excesses using, in particular, the atropisomeric ligand DIFLUORPHOS. This methodology allowed an efficient preparation of the anti phenylisoserine side chain of Taxotere which has been used for the hemisynthesis of the cancer therapeutic agent itself. In addition, 13C NMR in chiral oriented solvents was used to investigate the DKR effect.
- Prevost, Sebastien,Gauthier, Sebastien,De Andrade, Maria Cristina Cano,Mordant, Celine,Touati, Ali Rhida,Lesot, Philippe,Savignac, Philippe,Ayad, Tahar,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Genet, Jean-Pierre
-
experimental part
p. 1436 - 1446
(2010/11/03)
-
- METHOD OF PREPARING TAXANE DERIVATIVES AND INTERMEDIATES USED THEREIN
-
The present invention relates to a novel method of preparing a taxane derivative having an anti-tumor and anti-leukemia activity, and intermediates used therein.
- -
-
Page/Page column 6-7
(2010/12/29)
-
- PREPARATION OF DOCETAXEL
-
The present invention relates to docetaxel and processes for preparing docetaxel, including process-related intermediates. The present invention also relates to processes for preparing substantially pure docetaxel and intermediates.
- -
-
Page/Page column 24
(2010/07/10)
-
- METHOD OF PREPARING TAXANE DERIVATIVES AND INTERMEDIATES USED THEREIN
-
The present invention relates to a novel method of preparing a taxane derivative having an anti-tumor and anti-leukemia activity, and intermediates used therein.
- -
-
Page/Page column 15-16
(2008/12/06)
-
- Synthesis of taxoids 4. Novel and versatile methods for preparation of new taxoids by employing cis- or trans-phenyl glycidic acid
-
A novel route to the synthesis of docetaxel using esterification of (2R,3R)-or (2R,3S)-glycidic acid with 7,10-bis-O-(2,2,2- trichloroethoxycarbonyl)-10-deacetylbaccatin III is described. Related novel taxoids which have new side chains were synthesized from these synthetic intermediates.
- Yamaguchi, Tetsuo,Harada, Naoyuki,Ozaki, Kunihiko,Hayashi, Masahito,Arakawa, Hiroaki,Hashiyama, Tomiki
-
p. 1005 - 1016
(2007/10/03)
-
- Improved protection and esterification of a precursor of the taxotere and taxol side chains
-
(4S,5R)-N-BOC-2,2-dimethyl-4-phenyl-5-oxazolidinecarboxylic acid 8 was prepared and efficiently esterified by conveniently protected baccatins 9a,b. Smooth deprotection in formic acid gave the N-deprotected intermediates of Taxotere and taxol. This protocol did not generate any epimerization at C-2′ and constitutes a pratical method to prepare Taxotere, taxol and analogs.
- Commercon,Bezard,Bernard,Bourzat
-
p. 5185 - 5188
(2007/10/02)
-