Method for semi-synthesizing paclitaxel and docetaxel

A docetaxel, semi-synthetic technology, applied in the production of bulk chemicals, organic chemistry, etc., can solve the problems of low yield of final products and high production cost, and achieve the effects of easy realization, high yield and simple process

Inactive Publication Date: 2010-09-22
翟雄 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The currently disclosed method of synthesizing paclitaxel using 13-acetyl-9-dihydrobaccatin III as a raw material generally has problems such as low yield of final product and high production cost.

Method used

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  • Method for semi-synthesizing paclitaxel and docetaxel
  • Method for semi-synthesizing paclitaxel and docetaxel
  • Method for semi-synthesizing paclitaxel and docetaxel

Examples

Experimental program
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Embodiment 1

[0050] Step 1, the preparation of 9-dihydrobaccatin III (compound IM1)

[0051] 100g of 13-acetyl-9-dihydrobaccatin III (9-DHAB) was dissolved in 2L of tetrahydrofuran (THF), the temperature of the reaction system was lowered to -70°C, and then 600 ml of 1.6mol / l methyllithium was added dropwise into the reaction system and maintain the temperature of the reaction system at -70°C for 3 hours. Sampling was carried out to monitor the reaction, and until the raw materials were completely consumed, ammonium chloride solution was added to the reaction system to stop the reaction. The organic layer was washed with brine, dried and concentrated. The concentrate was recrystallized with 200 ml of dichloromethane, and filtered to obtain 74 g of 9-dihydrobaccatin III (compound IM1), with a yield of 80%.

[0052] Step 2, Preparation of 7-methyldiphenylsilyl-9-dihydrobaccatin III (Compound IM2)

[0053] 74g of compound IM1 and 35.3g of DMAP (4-dimethylaminopyridine) were dissolved in 1L o...

Embodiment 2

[0061] Step 1, the preparation of 9-dihydrobaccatin III (compound IM1)

[0062] Dissolve 100g of 13-acetyl-9-dihydrobaccatin III (9-DHAB) in 2L of tetrahydrofuran, lower the temperature of the reaction system to -70°C, and then add 600ml of 1.6mol / l methyllithium dropwise into the reaction system , the temperature of the reaction system was maintained at -70°C for 3 hours. Sampling was carried out to monitor the reaction, and until the raw materials were completely consumed, ammonium chloride solution was added to the reaction system to stop the reaction. The organic layer was washed with brine, dried and concentrated. The concentrated solution was recrystallized with 200 ml of dichloromethane, and 74 g of compound IM1 was obtained after filtration, with a yield of 80%.

[0063] Step 2, Preparation of 7-methyldiphenylsilyl-9-dihydrobaccatin III (compound IM2)

[0064] 74g of compound IM1 and 35.3g of DMAP were dissolved in 1L of dichloromethane, the temperature of the react...

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Abstract

The invention discloses a method for semi-synthesizing paclitaxel and docetaxel. The method for semi-synthesizing the paclitaxel sequentially comprises the following steps of: selectively stripping off C-13 acetyl of 13-acetyl-9-dihydro baccatin III to obtain a compound IM1; protecting C-7 hydroxy of the compound IM1 with a protective group to obtain a compound IM2; carrying out condensation reaction on the compound IM2 and a compound S1 and a compound S2 respectively to obtain a compound IM3 and a compound IM5; oxidizing C-9 hydroxy of the compound IM3 and the compound IM5 with oxidant to obtain a compound IM4 and a compound IM6 respectively; stripping off the C-7 protective group and the R3 protective group of the compound IM4 to obtain the paclitaxel; and stripping off the C-7 protective group, R3 protective group and acetyl of the compound IM6 to obtain the docetaxel. The method has the advantages of high yield of final products, low cost, and easy implementation.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a method for semi-synthesizing paclitaxel and docetaxel from 13-acetyl-9-dihydrobaccatin III. Background technique [0002] Cancer, also known as malignant tumors in medical terms, is a large class of diseases caused by abnormal control of cell growth and proliferation mechanisms, and has become one of the diseases that seriously endanger human health. In China, cancer has become the second leading cause of death after cardiovascular and cerebrovascular diseases. [0003] Paclitaxel is a diterpenoid compound isolated from the bark of the Taxus genus Taxus. It is a new type of microtubule stabilizer and has unique anticancer activity. Paclitaxel binds to cell tubulin, promotes tubulin polymerization and accumulates a large number of microtubules in cells. The accumulation of these microtubules interferes with various functions of cells, especially stops cell division in mitosis, blo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
CPCY02P20/55
Inventor 翟雄杨洋
Owner 翟雄
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