72 results about "10-Deacetylbaccatin" patented technology

A process for the preparation of taxanes comprising

wherein R is a tert. butoxycarbonyl or benzoyl group; PMP is p-methoxyphenyl group; G₁ is acetyl group; G₂ is haloacetyl group comprising

• • a) protecting the C-7 hydroxyl group of 10-deacetylbaccatin III with haloacetyl chlorides and then acetylating the C-10 hydroxyl group with acetyl chloride to obtain a protected 10-deacetylbaccatin III (1);
  • b) subjecting the protected 10-deacetylbaccatin III (1) to coupling with an oxazolidine-5-caboxylic acid of formula 2

wherein R is tert. butoxycarbonyl or benzoyl; PMP is p-methoxyphenyl group in the presence of a condensation agent and an activating agent to obtain C-13 esters of formula 3;

c) treating the coupled products 3 with weak acidic medium to open the oxazolidine ring to obtain intermediates of formula 4;

wherein R is a tert. butoxycarbonyl or benzoyl group; G₁ is acetyl group; G₂ is haloacetyl group

d) subjecting the intermediates of compound 4 to selective deprotection of haloacyl group in the presence of acetyl group under mild alkaline condition at −20 to +40° C. for 6-24 h in the presence of ammonia or aliphatic amine or aromatic amines or their combination to obtain paclitaxel or docetaxel.

The invention relates to a method for using specific resin and silicon gel column chromatography purification via negative pressure cavitation water extraction to high-efficiency produce 10-deacetylbaccatin III and 7-xylose-10-deacetylpaclitaxel, which uses taxus branch leaves as raw material, dries and breaks to process negative pressure cavitation water extraction, filters and uses AB-8 resin to process dynamic absorption on filter liquor to concentrate 10-deacetylbaccatin III and 7-xylose-10-deacetylpaclitaxel and process further purification via middle pressure silicon gel column chromatography, to obtain the 10-deacetylbaccatin III of at least 60% purity and 7-xylose-10-deacetylpaclitaxel of at least 67% purity. The invention can use renewable taxus branch leaves to protect ecological resource and effectively extract effective component and biological semi synthesis precursor materials, with simple operation, support for industrial application and important industrial production value.

The invention relates to 10-deacetylbaccatin III and a method for methoxylation of its derivative, which belongs to the medicine synthesis technical field. The invention is characterized in that the under the condition that 10-DAB, the 7 position and the 10 position of its derivative are hydroxy or one of them is hydroxyl, a phase transfer catalyst quaternary ammonium salt N<+>R4X<-> is added under the existence of a methylating agent, and dissolved according to a weight ratio of 1:10-100 of solute to organic solvent, and reacted with low temperature, a lower layer water phase is separated after finishing the reaction, an organic phase is washed by a saturated salt solution, and the organic phase is concentrated by concentrated acid, a petroleum ether is added for completely deposing, filtered, deposed and dried to obtain the product. The invention provides a simple and easy method for preparing the 10-DAB and a methoxy compound of the 7 position and the 10 position hydroxy of its derivative. The method for large scale intermediate preparation enables possibility of preparation of docetaxel with large dosage, and is a key step for preparing cabazitaxel.

The invention relates to a 10-deacetylbaccatin-9(R)-hydrogenation-1-deoxidized paclitaxel analog and a preparation method thereof. The structural formula of the analog is as the right; in the method of the invention, 1-deoxidized baccatin VI is taken as a material for synthesizing the 1-deoxidized paclitaxel analog. The method of the invention maintains the ring skeleton and the necessary functional group of taxanes and selects the taxanes as a semi-synthetic precursor or carries out structure decoration on the taxanes; the obtained output 10-deacetylbaccatin-9(R)-hydrogenation-1-deoxidized paclitaxel analog has the biological activity of antitumor of the natural paclitaxel and has a certain application prospect in the aspects of reducing the multidrug resistance and the side effects of the natural paclitaxel. The method has the advantages of easily obtained materials, simple and convenient operation, good selectivity and high yield.

The invention discloses a method for extracting 10-deacetylbaccatin III from taxus chinensis. The method comprises the following steps: soaking and extracting 10-deacetylbaccatin III in taxus chinensis by adopting an aqueous solution containing a stability maintainer; and extracting, performing discoloring and flocculating treatment, recrystallizing and the like, thereby obtaining the high-purity10-deacetylbaccatin III. The method disclosed by the invention is clean, low in cost, non-harsh in extraction conditions, less in by-products, less in pigments and high in extraction rate, and is applicable to industrialized production and market popularization and application.

A process is provided for the semi-synthesis and isolation of taxane intermediates useful in the preparation of paclitaxel and docetaxel, in particular, the semi-synthesis and isolation of 10-deacetylbaccatin III, the semi-synthesis of a mixture of 10-deacetylbaccatin III and baccatin III, and protected derivatives thereof, from a mixture of taxanes.

The invention provides a preparation method of docetaxel. The method comprises the following steps: 1) dissolving 10-deacetylbaccatin III in an solvent, and reacting with a protective agent to selectively protect the 7-hydroxyl group and 10-hydroxyl group in the 10-deacetylbaccatin III; 2) preparing a side chain intermediate; 3) performing an esterification reaction on the products obtained in the step 1) and the step 2); 4) removing the protective groups on the side chain of the esterification product under the acidic condition; 5) protecting amino on the side chain with the protective group under the alkaline condition; and 6) removing the protective groups on the hydroxyl groups to produce docetaxel. The invention provides the new preparation method of docetaxel, wherein the new related side chains are synthesized to prepare docetaxel; and the method has significances to utilize various taxanes which are extracted and separated from natural products and have similar structures with the target compound, optimize the technological process, increase the yield, reduce the cost, reduce the product price, comprehensively utilize resources and the like.

A process is provided for the semi-synthesis and isolation of taxane intermediates useful in the preparation of paclitaxel and docetaxel, in particular, the semi-synthesis and isolation of 10-deacetylbaccatin III, and protected derivatives thereof, from a mixture of taxanes.

A novel process of making 7,10-dialkyl-10-DAB of formula (I)

which is useful as a key intermediate for the preparation of cabazitaxel, comprises selective elaboration of positions 7 and 10 of 10-deacetylbaccatin III.

A process for the preparation of taxane derivatives by reacting 10-deacetylbaccatin III protected at the 7-and 1-positions with trichloroacetyl groups with a compound of formula

and subsequent removal of the protective groups and hydrolysis of the oxazolidine ring.

The invention discloses a method for improving yield of 10-deacetylbaccatin III produced by fungi. The method comprises the following steps: culturing in a culture medium to produce 10-deacetylbaccatin III, specifically, culturing at 25 DEG C for three days, then culturing at 10 DEG C for six hours, then culturing at 25 DEG C for 12 hours, and then culturing at 30 DEG C for six hours, and circulating like this at 12 variable temperatures. Therefore, the yield of 10-deacetylbaccatin III produced by fungi is stimulated by circulating excitation of high and low temperatures. Compared with the traditional culturing method, the method provided by the invention has the advantages that the yield of 10-deacetylbaccatin III is obviously improved, the operation is simple, the production cost is low, the purpose of improving the yield is achieved simply by changing the temperature, and the yield of 10-deacetylbaccatin III can be improved by 2.4 times.

9-dihydro-13-acetylbaccatin III, one of the chemicals obtained from Taxus canadensis is used to produce, inter alia, 10-decetylbaccatin III, a useful intermediate for the preparation of paclitaxel and analogues thereof The 9-dihydro-13-acetylbaccatin III is converted into the 10-deacetylbaccatin III by a simple three step process involving (a) replacement of the C-7 hydroxyl group of the 9-dihydro compound with a protecting group, (b) the oxidizing of the C-7 protected compound to produce a C-9 keytone, and (c) the deprotecting of the C-9 keytone to produce 10-deacetylbaccatin III

The invention relates to a method for semisynthesis of Docetaxel and an intermediate of the Docetaxel. The method provided by the invention comprises the steps of firstly, carrying out hydroxyl protection on C7 and C10 of 10-DAB III (10-deacetylbaccatin III) by using 2,2,2-trichloroethylchloroformate so as to obtain an intermediate I, subjecting the intermediate I to a reaction with a side chain radical compound so as to prepare an intermediate II, subjecting the intermediate II to a hydrogenation reaction under the catalysis of palladium-charcoal so as to prepare an intermediate III, subjecting the intermediate III to a reaction under acidic conditions so as to obtain a Docetaxel crude product, and subjecting the Docetaxel crude product to purification, thereby obtaining a purified product. According to the method provided by the invention, the 10-DAB III raw material can be sufficiently utilized, finally-produced byproducts are few, the final product Docetaxel has the purity of 99.6% to 99.9%, the mole yield reaches up to 73% to 82%, and the utilization ratio of the 10-DAB III can be greatly increased.

The invention relates to a semi-synthesis method of antitumor drug taxol, and more particularly relates to a method for preparing taxol by the processes of taking 10-deacetylbaccatin III (10-DAB) as an initial material, selective acetylation, protection, condensation, open loop, and deprotection.

A disclosed crystallization purification method for 10-deacetylbaccatin III (10-DAB III) is performed according to the following steps: a, adding acetone into a 10-DAB III crude product, and performing ultrasonic stirring so as to completely dissolve 10-DAB III; b, adding acetonitrile when 10-DAB III is in the state of ultrasonic stirring, and filtering after a crystal is precipitated, so as to obtain a wet crystal; and c, drying the wet crystal, so as to obtain a high-purity 10-DAB III crystal. According to the crystallization purification method for 10-DAB III, by employing the acetone-acetonitrile mixed solvent for crystallization, the purity of the 10-DAB III crude product possessing the purity of 35% and being subjected to once crystallization is improved to 90% or more, the yield is 65% or more, the crystal purity is high, the yield is high, and the method is simple and convenient to operate, and helps to substantially improved the purification yield of 10-DAB III.

The invention provides a preparation method for a docetaxel impurity, namely, 10-dichloroethoxycarbonyl docetaxel. The preparation method comprises the following steps: (1) taking 7-triethyl silicon-10-deacetylbaccatin III as a raw material and reacting with chloroformic-2,2-dichloro ethyl ester, thereby acquiring a product I; (2) triggering the product I to react with polysillic acid under the effect of a condensing agent, thereby acquiring a product II; (3) triggering the product III to react under the effect of hydrochloric acid, thereby acquiring the 10-dichloroethoxycarbonyl docetaxel. The method is simple in operation, high in yield and high in product purity. The acquired product has a great significance in researching docetaxel quality.