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Method for separating and preparing paclitaxel

A technology for paclitaxel and taxane, which is applied in the field of preparation of paclitaxel raw materials, can solve the problems of unusable price, strong carcinogenicity and high cost, etc.

Active Publication Date: 2010-12-29
ZHANGJIAGANG IND TECH RES INST CO LTD DALIAN INST OF CHEM PHYSICS CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, OsO 4 The strong carcinogenicity and high price determine that this process cannot be used for the industrial production of paclitaxel raw materials

Method used

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  • Method for separating and preparing paclitaxel
  • Method for separating and preparing paclitaxel
  • Method for separating and preparing paclitaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Weigh 1.0g taxane sample (containing 37% paclitaxel, 21% cephalomannine) and dissolve in 20ml methanol, add 220mg NBS and add Lewis acid, react at room temperature, HPLC detection shows cephalomannine conversion rate After reaching 95%, the feed liquid was evaporated to dryness under reduced pressure. Dissolve about 8 ml of ethyl acetate-n-hexane (1:1) and apply to the column for separation, and elute with ethyl acetate / n-hexane (1:1). The paclitaxel (purity > 90%) fraction was obtained by classifying and collecting each fraction. Adopted various Lewis acids and their consumption, reaction time, paclitaxel yield list are as follows:

[0043] Table 1. Various Lewis acids catalyze the addition of monobromomonoalkoxy groups

[0044]

Embodiment 2

[0046] Take by weighing 1.0g taxane sample (containing 37% paclitaxel, 21% cephalomannine) and dissolve in 40ml methanol: water (3:1) system, add 220mg NBS, react at 35 ℃ for 12 hours, HPLC detection shows The conversion rate of cephalomannine reaches 95%. After the addition reaction, the product was extracted three times (40ml, 10ml, 10ml) with ethyl acetate-n-hexane (1:1), and the extracts were combined and concentrated. The concentrated solution was dissolved in about 8 ml of ethyl acetate-n-hexane (1:1), and then separated by column loading, and eluted with ethyl acetate / n-hexane (5:5). The fractions of paclitaxel were collected by classification to obtain 378mg of paclitaxel with a purity of 91%. Yield 93%.

Embodiment 3

[0048] Weigh 5.00g taxane sample (37% paclitaxel, 21% cephalomannine) and dissolve it in 100ml methanol, add 10ml water and 1g NBS, react at 35°C until cephalomannine disappears, the product is washed with ethyl acetate Ester-n-hexane (1:1) extracted three times (80ml, 40ml, 20ml), combined and concentrated. The concentrate was dissolved in 40 ml of ethyl acetate-n-hexane (1:1) and separated by column. Ethyl acetate / n-hexane (5:5)-ethyl acetate / n-hexane (4:6) was used for elution. After sorting and collecting, 1.65 g of the paclitaxel fraction was obtained, with a purity of 90%. Yield 89%.

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Abstract

The invention relates to an application of cephalomannine chemical derivation method in taxol preparation, comprising the following steps that: cephalomannine analogues having an alpha-beta unsaturated ketone structure are converted into a single-halogen single-hydroxyl or single-halogen single-alkyl product through addition reaction, and then taxol is obtained through column separation. The process is also suitable for the separation of 10-deacetylated cephalomannine, 10-deacetylated taxol, 10-deacetylated-7-xylose cephalomannine and 10-deacetylated-7-xylose taxol. The application has the advantage of applying an NBS addition method to the separation of taxol and cephalomannine (or analogues of the two) successfully, and using a conventional cheap silica gel column to realize the separation of taxol and cephalomannine so as to achieve the aim of purifying taxol. The method is suitable for the taxol mixtures with different purity and can be used for the separation of other cephalomannine type compounds and analogues. Due to the process of the invention, the taxol with the purity more than 99 percent can be obtained; the overall yield can be up to 80 percent; the overall yield of cephalomannine addition products is over 90 percent.

Description

technical field [0001] The invention relates to the field of preparation of paclitaxel raw materials, and in particular provides an application of a cephalomannine chemical derivation method in the preparation of paclitaxel. Background technique [0002] Taxol was first isolated from the bark of Taxus brevifolia in 1967. At present, paclitaxel has been approved by the US FDA for the treatment of solid cancers such as breast cancer, ovarian cancer and non-small cell lung cancer (Lancet, 2000, 355, 1176). The content of paclitaxel in the Taxus genus plant extract is extremely low; there are a wide variety of coexisting impurities, especially the analog cephalomannine ( Picture 1-1 ,2). Since they have the same core, the only difference in structure is the substituent on the 3'-amide, paclitaxel is phenyl, and cephalomannine is 2-butenyl. The similarity in structure also determines their similar physical and chemical properties and chromatographic retention behavior, so it i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D305/14
Inventor 杨凌葛广波张延延榊原和征
Owner ZHANGJIAGANG IND TECH RES INST CO LTD DALIAN INST OF CHEM PHYSICS CHINESE ACADEMY OF SCI
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