Process for preparing high purity taxol by column bromating method

A paclitaxel and high-purity technology, applied in the field of paclitaxel technology, can solve the problems of difficult determination of reaction time and temperature, incomplete reaction of cephalomannine, incomplete reaction time, etc., so as to improve the utilization rate of bromine, and has the advantages of Conducive to mass production and environmental protection

Inactive Publication Date: 2003-11-26
FUDAN UNIV
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  • Abstract
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AI Technical Summary

Problems solved by technology

[0005] The structure of cephalomannine is similar to paclitaxel, the only difference is that its C-13 side chain end is a butenyl group instead of the benzene ring in the structural formula of paclitaxel, and paclitaxel is obtained by column chromatography, normal pressure and low pressure chromatography and cephalomannine, but it is difficult to completely separate paclitaxel by conventional column chromatography
In this method, the time for the bromine solution to pass through the sample is largely affected by the packing of the silica gel column, and the reaction time between the sample and the bromine in the column is not completely consistent, which may easily cause the incomplete reaction of cephalomannine or the product to be eliminated. Situation of bromination
It is difficult to determine the reaction time and temperature of the bromine solution when passing through the sample
These issues add to the uncertainty of the response

Method used

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  • Process for preparing high purity taxol by column bromating method
  • Process for preparing high purity taxol by column bromating method
  • Process for preparing high purity taxol by column bromating method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] 100-200 mesh silica gel is baked at 110°C for 2 hours, take 25 grams and put it into 20×300mm 2 In a glass chromatography column, fill it up. Take by weighing 1.000 gram paclitaxel crude extracts (detect with HPLC, record the peak area content of each material in the raw material and be: paclitaxel 37.88%, cephalomannine 43.84%, 7-table-10-deacetyl paclitaxel 4.83%) , add 5ml chloroform to dissolve. Add 0.08ml of liquid bromine in an ice-water bath, keep away from light, and continuously stir, and after reacting for 5 minutes, pour the reaction solution into the installed silica gel column. First use 80mlCCl 4 Rinse to remove excess bromine in the reaction, and then elute with chloroform reagent. Each part of cuts collected is detected with HPLC, (chromatographic column filler is C 18 ), according to the detection situation, the fractions with a paclitaxel content of more than 85% were collected, concentrated, evaporated to dryness, and weighed to obtain 0.3181 gram...

Embodiment 2

[0048] Take by weighing 0.9976 gram paclitaxel crude extract (detect with HPLC, record the peak area content of each material in the raw material to be: paclitaxel 37.88%, cephalomannine 43.84%, 7-table-10-deacetyl paclitaxel 4.83%) , add 5ml chloroform to dissolve. Add 0.08ml of liquid bromine in an ice-water bath, keep away from light, and continuously stir, and after reacting for 5 minutes, pour the reaction solution into the installed silica gel column. First use 80mlCCl 4 Rinse to remove excess bromine in the reaction, then rinse with 500ml of 1:1 ethyl acetate and n-hexane solution, and finally use 100ml of ethyl acetate reagent to elute other impurities. Perform HPLC detection on each part of the fractions. According to the detection situation, more than 85% of paclitaxel fractions, more than 90% of 2”, 3”-dibrominated cephalomannine fractions, and paclitaxel and 2”, 3”-dibrominated The mixed fractions of cephalomannine were collected separately, and these three parts...

Embodiment 3

[0051] Take 2700 grams of 100-200 mesh dry silica gel and fill it into 100×1000mm 2 In the glass chromatography column, the packing height is 800mm. Take by weighing 54.13 grams of paclitaxel crude extracts (detected by HPLC, the peak area content of each material recorded in the raw material is: paclitaxel 42.14%, cephalomannine 42.61%, 7-table-10-deacetyl paclitaxel 7.16%) . The actual mass percentage of paclitaxel was determined to be 31.5% by external standard method, that is, 17.05 grams of paclitaxel in the raw material. Add 200ml chloroform to dissolve. In an ice-water bath, protected from light, and continuously stirred, add 3.5ml of liquid bromine, react for 5 minutes, and pour the reaction solution into the installed silica gel column. First use 3L of CCl 4 Rinse to remove excess bromine in the reaction, then rinse with 50L of 1:1 ethyl acetate and n-hexane solution, and finally use pure ethyl acetate reagent to elute other more polar impurities. The eluate abov...

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Abstract

The present invention is column bromating process of preparing high purity taxol. The coarse taxad extractive containing cephalotmannine is made to react with bromine, the bromide of cephalotmannineand concomitant product are then eliminated through forward filling chromatographic column separation, and through further twice re-crystallization, high purity taxol is prepared in the total yield of 85 %. Taxol with relatively lower purity is transferred to forward silica gel column for further separation. The said process is suitable for large scale production. The reagent and the solvent are recovered for reuse, and this is favorable to environment protection.

Description

technical field [0001] The invention relates to a paclitaxel process, in particular to a process for preparing high-purity paclitaxel by a column bromination method. Background technique [0002] Wall et al. reported for the first time in 1971 that paclitaxel was isolated from the bark of Taxus chinensis, and confirmed that it had anticancer activity (J.Am.Chem.Soc., 93, 2325, 1971). In 1983, the National Cancer Institute (NCI) of the United States reported that paclitaxel had anti-tumor effects on solid cancers such as human breast cancer and colon cancer. In 1993, the US FDA approved the clinical application of the drug for the treatment of conventional chemotherapy, including ovarian cancer and breast cancer, and for the treatment of lung cancer and other cancers. Paclitaxel is considered to be the most significant discovery in the field of natural anticancer drug research in the past 30 years, bringing good news to cancer patients. [0003] The research on cephalomanni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
CPCY02P20/582
Inventor 陈建民金晓英李明姜毅吴蓓莉郑志坚
Owner FUDAN UNIV
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