Taxone bromated analog with anticancer activity and preparation method thereof

An anticancer activity, taxane technology, applied in the field of medicine

Inactive Publication Date: 2006-01-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] This structural nuance leads to a similarity in the chromatographic behavior of cephalomannine to paclitaxel, which is difficult to separate by conventional chromatography, but also provides selective oxidation of the double bond at the end of the C13 side chain, separating the three The conversion of cephalomannine into a compound whose chromatographic behavior is quite different from that of paclitaxel, thus realizing the possibility of chromatographic separation

Method used

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  • Taxone bromated analog with anticancer activity and preparation method thereof
  • Taxone bromated analog with anticancer activity and preparation method thereof
  • Taxone bromated analog with anticancer activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Bromination of partially purified mixtures containing 7-epi-10-deacetyl-cephalomannine, cephalomannine and other taxanes

[0064] 3 g of the crude extract of Taxus chinensis was dissolved in 30 ml of chloroform under the action of a magnetic stirrer, and cooled in an ice-water bath for 0.50 hour. Slowly add 100 μl of liquid bromine dropwise to the three reaction vessels respectively, and react in an ice-water bath at 0° C., protected from light, and stirred. From the dropwise addition of liquid bromine reaction, every 10min, quantitatively pipette 1ml of the reaction solution from the reaction vessel into the separatory funnel, and then add 5ml of 10% Na 2 S 2 o 3 The solution reduces excess bromine therein. Use a dry 5ml small test tube to collect the lower organic phase, pipette 0.50ml of the solution from the separated organic phase into a dry eggplant-shaped bottle, evaporate to dryness at room temperature, dissolve in 2.50ml of methanol, and detect with HPLC . ...

Embodiment 2

[0066] Normal Phase Preparative Chromatographic Separation of Bromination Reaction Products

[0067] Dissolve 3 g of the above reaction mixture in 50 ml of 1:1 ethyl acetate and n-hexane, use a P280 high-pressure constant-flow pump to inject the sample, and use ethyl acetate:n-hexane (1:1~1:1.5) as the flow equal degree elution , A total of 30 bottles of fractions were collected, 100ml / bottle. The fractions were evaporated to dryness under reduced pressure and detected by reverse phase HPLC. All the fractions were divided into 3 parts and merged respectively, wherein fractions 1 to 10 were mainly two diastereoisomers of 2", 3"-dibromo-7-table-10-deacetyl-cephalomannine, Fractions 11-22 are mainly two diastereoisomers of 7-table 10-deacetyl paclitaxel and 2”, 3”-dibromocephalomannine, and fractions 23-30 are high-purity paclitaxel. The individual fractions were evaporated to dryness under reduced pressure. The chromatogram of the normal phase preparation process and the resu...

Embodiment 3

[0069] Separation of individual diastereoisomers of 2", 3"-dibromo-7-epi-10-deacetyl-cephalomannine and 2", 3"-dibromocephalomannine

[0070] The separation of the individual diastereoisomers of 2", 3"-dibromo-7-epi-10-deacetyl-cephalomannine and 2", 3"-dibromocephalomannine was by reversed-phase semi-preparative high-performance liquid chromatography system. 100 mg of dried solid mainly containing two diastereoisomers of 2", 3"-dibromo-7-epi-10-deacetyl-cephalomannine were dissolved in 1.5 ml of methanol, and then The sample was washed with water: acetonitrile (60:40) mobile phase, and the two diastereoisomers elute at 27.3 min and 29.1 min, respectively. The separation process of the diastereoisomers of single 2", 3"-dibromocephalomannine is basically the same as the above-mentioned process. After the injection, the mobile phase of water: acetonitrile (62:38) is used for elution, and the two Two diastereomers elute at 28.4 min and 29.6 min. The four individual diastereome...

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Abstract

The present invention relates to taxane bromo-analogues with anticancer activity and preparation method thereof. It uses bromine and taxus crude extract containing cephalotmannine and 7-epi-10-deacetyl cephalotmannine to make addition reaction, then uses normal-phase preparation-type HPLC and reversed-phase semi-preparation HPLC to obtain two new taxane analogues: (2''R,3''S)-dibromo-7-epi-10-deacetyl cephalotmannine and (2''S,3''R)-dibromo-7-epi-10-deacetyl cephalotmannine. As compared with taxol said two analogues have similar and stronger anticancer activity for human mammary cancer cell (MCF-7), human pulmonary carcinoma cell (A549) and human oophoroma cell (A2780), and can be used for preparing anticancer medicine.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a brominated taxane analog with anticancer activity and a preparation method thereof. Background technique [0002] Wall et al first reported paclitaxel (I) isolated from the bark of Taxus chinensis in 1971, and confirmed that it has 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 FDA approved the drug for the treatment of ovarian and breast cancer. 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 structure of cephalomannine (II) is similar to paclitaxel, the only difference is that its C13 side chain end is an unsaturated alkenyl group in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D305/14A61K31/337A61P35/00
Inventor 陈建民姜毅李明金晓英林海霞吴蓓莉
Owner FUDAN UNIV
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