Preparation of 10-deacetyl 7-xylose baccatin or 7-xylose baccatin

A technology for removing acetylation and xylose, which is applied in the fields of sugar derivatives, bulk chemical production, organic chemistry, etc., to achieve the effects of simple process, wide application range and low cost

Inactive Publication Date: 2008-03-12
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 1993, Carver et al. developed a method for removing the C-13 group of taxane by using borohydride and Lewis acid together. Under anhydrous solvent system, borohydride, especially organic borohydride and Specific Lewis acids can convert taxanes into baccatin or 10-DAB under low temperature conditions, but this process does not include 7-xyloside taxanes in the scope of protection (US5256801, US5202448)

Method used

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  • Preparation of 10-deacetyl 7-xylose baccatin or 7-xylose baccatin
  • Preparation of 10-deacetyl 7-xylose baccatin or 7-xylose baccatin
  • Preparation of 10-deacetyl 7-xylose baccatin or 7-xylose baccatin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Conversion of 10-DAXT to 10-DAXB

[0043] 1.0 g of 7-xylose taxane mixture containing 10-deacetyl 7-xylose paclitaxel (51%) was dissolved in 10 ml of THF, and 0.36 g of NaBH was added 4 , after stirring for 2 hours, the reactant was poured into 50% acetic acid-water solution, stirred for 10 minutes, and NaBH that did not participate in the reaction was removed 4 , and extracted three times with ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate for 6 hours. After filtration, it was concentrated to obtain 1.12 g of crude product with a 10-DAXB content of 54%.

Embodiment 210-D

[0044] Purification of embodiment 2.10-DAXB

[0045] Pack 15 grams of silica gel into a column (column diameter 1.9 cm, column bed height 9.5 cm), dissolve 1.12 grams of 10-DAXB crude product in dichloromethane; use 90% dichloromethane / methanol as eluent, elute 800 ml and then TLC After testing and concentrating the same components, 0.47 g of 85% 10-DAXB was obtained with a yield of 112% (the raw material contains other xylose taxanes). Dissolve 0.47 g of 85% 10-DAXB in 40 ml of hot ethanol, add 5 ml of triple-distilled water dropwise under ultrasound; leave it at room temperature for 6 hours, then move it to the refrigerator for 24 hours and filter to obtain 0.33 g of white crystals. The purity was determined by HPLC 95%, the mother liquor continues to crystallize to obtain high-purity 10-DAXB:

Embodiment 3

[0046] Example 3: Conversion of 10-DAXC to 10-DAXB

[0047] 0.10 g of 10-deacetyl 7-xylose cephalomannine (91%) was dissolved in 2 ml of THF, and 0.04 g of (Me) 4 NBH 4 , stirred at room temperature for 2 hours. After the reaction, the reactant was poured into cold glacial acetic acid-water solution and stirred for 10 minutes to remove NaBH that did not participate in the reaction. 4 . Extracted 3 times with ethyl acetate, combined the organic phases and dried over anhydrous sodium sulfate for 6 hours. After filtration and concentration, 0.11 g of 87% 10-DAXB was obtained.

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Abstract

The present invention relates to the prepation of 10 - acetyl 7 - baccatin xylose or 7 - xylose baccatin. 7 - xylose taxanecompounds with C-13 side chain are used as the raw materials; the product 10 - acetyl 7 - baccatin xylose or 7 - xylose baccatin is achieve through the selective deoxidization reaction of borohydride which removes the C-13 side chain from the C-13 ester. The present invention has the advantages of low manufacturing cost, high efficiency and controllable cleaning. The present invention is suitable for the mass production of 10-DAXB and XB.

Description

technical field [0001] The invention relates to a preparation process of an important taxane intermediate (10-deacetyl) 7-xylose baccatin. Under the action of borohydride, the C-13 side chain of taxane 7-xylosides can be removed and transformed into 10-deacetyl 7-xylose baccatin (10-DAXB) or 7-xylose Baccatin (XB). The obtained compound can be converted into baccatin or 10-deacetylbaccatin (10-DAB), the key intermediate semi-synthesized of paclitaxel and docetaxel after hydrolysis of the 7-position xylosyl group, and this product can also be used to synthesize other drugs with special pharmacological properties. active taxanes. Background technique [0002] Taxanes are a class of diterpenoids, widely present in the stems, leaves and bark of Taxus plants, and more than 300 taxane diterpenoids have been isolated (J.Nat.Prod.1999, 62 , 1448). Paclitaxel isolated from Taxus and its semi-synthetic analogue docetaxel are currently widely used in the treatment of breast cancer,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/04C07D305/14
CPCY02P20/55
Inventor 杨凌葛广波张延延
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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