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Method for preparing taxanes by epimerization biological transformation 7-epimer taxanes

A biotransformation and taxane technology, applied in the direction of fermentation, etc., can solve the problems of low economic value, multiple products or unclear results, expensive reagents, etc.

Inactive Publication Date: 2007-11-28
YUNNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are reports of chemical conversion of 7-epimine taxane methods, the conversion reactions in these reports have formed multiple products or unclear results, and the reagents used are expensive (Kuang Yunyan et al., Chinese Journal of Medicinal Chemistry, 2005, 64 (2 ): 94-96; Zhang Zhiqiang et al., Acta Biological Engineering, 2000, 16(3): 378-382), with little economic value

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1: 1000ml of soybean flour medium was evenly distributed in 10 500ml Erlenmeyer flasks, and after cultivating at 28°C at 160rpm for 3 days, 0.1g of 7-epitaxel was dissolved in 100ml of dimethylformamide DMF . Add 10ml of N,N-dimethylformamide (DMF) solvent containing the substrate into each conical flask, transform on a shaker at 28°C at 160rpm for 3 days, combine the transformed cultures, and centrifuge the fermentation broth to obtain slag and fermentation broth. liquid, the fermentation supernatant was absorbed with 200 grams of Amberlite XAD-16 macroporous resin, with 4 times the volume of 10-30% methanol: water to wash the macroporous resin, and then with 5 times the volume of 30%-100% methanol solution Macroporous resin, the flushing liquid of this section was concentrated under reduced pressure to obtain a brown mixture. About 20 grams of the wet residue was extracted three times by adding 100 ml of acetone three times, and concentrated under reduced pre...

Embodiment 2

[0015] Example 2: 1000 ml of cultured Bacillus subtilis beef extract peptone medium was centrifuged to obtain 5 grams of wet bacteria, which were embedded in sodium alginate and packed into an immobilized cell column. Dissolve 1 g of 10-deacetyl-7-epitaxel in 100 ml of dimethyl sulfoxide (DMSO), then add 900 ml of water and 10 g of glucose, add the sample solution from the top of the column, control the flow rate to 4 drops per minute, the first 10 Hours of transformation solution was added back to the top of the column. The conversion solution was collected, concentrated under reduced pressure to evaporate the solvent, and 5 g of the conversion product was obtained, containing 0.41 g of 10-deacetylpaclitaxel, and the conversion rate was 41%.

Embodiment 3

[0016] Embodiment 3: after the cultured 3000ml Mucor echinocystis is broken through ultrasonic cell, 20%-500% by weight of ammonium sulfate is precipitated to obtain 25 grams of invertase, after the obtained invertase is adsorbed with macroporous resin, Column packing. Dissolve 1 gram of 10-deacetyl-7 epitaxel in 100ml of methanol, then add 900ml of water, add the solvent containing the substrate from the top of the immobilized column, and flow out from the lower end, the flow rate is controlled at 2 drops per minute. Concentrate the solution under reduced pressure to obtain 2 g of a mixture of converted product and unconverted substrate, containing 0.35 g of 10-deacetylpaclitaxel, which becomes paclitaxel after acetylation. Unconverted substrates can be reconstituted to continue the transformation.

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Abstract

The present invention relates to a method of forming taxane diterpene by difference transformation 7- taxane using microorganisms. The present invention comprised the following steps: 1. Completely dissolve the 7- taxane compound which has a content of over 1% into the organic solvent that can be mixed with water at any ratio; 2. Add the solution of step 1 into the microbes biological culture, or abstraction enzyme from themicro-organism. An alternative is that after the extractenzyme immobilization, the solution of step 1 is added and the conversion time is 3-100 hours; 3. Extract taxane diterpene using conventional methods from the convert product of step 2. The technical problem solved in this invention is that the no valueble 7- taxane is converted into a valuble enantiomer, so as to save the resources of Yew.

Description

technical field [0001] The invention relates to a method for converting 7-epimine taxane into taxane by means of microorganism epigenesis. technical background [0002] Paclitaxel is an expensive anticancer drug extracted from the yew plant, and the production raw materials are seriously insufficient, resulting in high prices of paclitaxel. By biotransformation, the 7-epimized taxanes, which currently have no medicinal value and are present in a large amount in the branches and leaves of Taxus chinensis, are converted into paclitaxel and the precursor of paclitaxel that can be used for semi-synthesis, which can increase the yield of paclitaxel. Has great economic value. There are many kinds of epitaxane compounds, among which 7-epitaxol, 10-deacetyl-7-epitaxol, 7-epiacephalomannine, 10-deacetyl-7- Different to tricuspid Shanning, 10-deacetyl-7-different to baccatin III and so on. Their common feature in structure is that the 7-position hydroxyl group on the taxane mother ...

Claims

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Application Information

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IPC IPC(8): C12P17/02
Inventor 王兴红李松
Owner YUNNAN UNIV
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