Method for separating and preparing paclitaxel

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

Active Publication Date: 2008-11-19
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

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Problems solved by technology

However, OsO 4 The strong carcinogenicity and high price determine that this p

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
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Embodiment 1

[0039] Weigh 1.0g taxane sample (containing 37% paclitaxel, 21% cephalomannine) and dissolve it in 20ml methanol, add 220mg NBS and Lewis acid, and react at room temperature. HPLC detection shows the conversion rate of cephalomannine After reaching 95%, the material liquid was evaporated to dryness under reduced pressure. After dissolving in about 8 ml of ethyl acetate-n-hexane (1:1), the sample is separated on the column, and eluted with ethyl acetate / n-hexane (1:1). Separately collect each component to obtain paclitaxel (purity>90%). The various Lewis acids used, their dosage, reaction time, and paclitaxel yield are listed as follows:

[0040] Table 1. The addition of monobromomonoalkoxy catalyzed by various Lewis acids

[0041]

Embodiment 2

[0043] Weigh 1.0g taxane sample (containing 37% paclitaxel, 21% cephalomannine) and dissolve it in 40ml methanol:water (3:1) system, add 220mg NBS, and react at 35℃ for 12 hours. HPLC detection shows The conversion rate of cephalomannine is 95%. After the addition reaction, the product was extracted three times (40ml, 10ml, 10ml) with ethyl acetate-n-hexane (1:1), and the extracted phases were combined and concentrated. The concentrated solution was dissolved in about 8 ml of ethyl acetate-n-hexane (1:1), and then separated on a sample column, and eluted with ethyl acetate / n-hexane (5:5). Separately collect each component to obtain 378 mg of paclitaxel with a purity of 91%. The yield was 93%.

Embodiment 3

[0045] Weigh 5.00g taxane sample (37% paclitaxel, 21% cephalomannine) and dissolve it in 100ml methanol, add 10ml water and 1g NBS, react at 35℃ until cephalomannine disappears, and use ethyl acetate as the product Ester-n-hexane (1:1) was extracted three times (80ml, 40ml, 20ml), combined and concentrated. The concentrated solution was dissolved in 40 ml of ethyl acetate-n-hexane (1:1) and separated by column. Elute with ethyl acetate / n-hexane (5:5)-ethyl acetate / n-hexane (4:6). After separate collection, 1.65 g of paclitaxel was obtained, with a purity of 90%. The yield was 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 the preparation of paclitaxel raw materials, and in particular provides an application of a cephalomannine chemical derivatization method in the preparation of paclitaxel. Background technique [0002] Paclitaxel 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 breast cancer, ovarian cancer and non-small cell lung cancer and other solid cancers (Lancet, 2000, 355, 1176). The content of paclitaxel in the extracts of Taxus plants is extremely low; there are many kinds of coexisting impurities, especially the molecular structure and physical and chemical properties of paclitaxel, which is very similar to paclitaxel analogue cephalomannine ( Picture 1-1 ,2). Since they have the same core, the only difference in structure is the substituents on the 3'-amide, paclitaxel is a phenyl group, and cephalomannine is a 2-butenyl group. The simi...

Claims

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Application Information

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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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