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Method for synthesizing taxol side chains

A technology of paclitaxel side chain and synthesis method, which is applied in chemical instruments and methods, preparation of organic compounds, production of bulk chemicals, etc., can solve the problems of low yield, high cost, long route and the like, and achieves high yield and easy access. Easy to control and synthesize effects

Active Publication Date: 2013-07-31
SHANGHAI JINHE BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to provide a method for synthesizing paclitaxel side chains with lower production costs in view of the defects of long route, need for resolution, low yield and high cost in the existing numerous patents

Method used

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  • Method for synthesizing taxol side chains
  • Method for synthesizing taxol side chains
  • Method for synthesizing taxol side chains

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 1, the preparation of the compound of structural formula 2

[0029] Get a dry single-necked round bottom flask and place it on the oil bath, cis-epoxy compound 1 (1.78g, 10mmol, methyl ester), low-pressure freeze-dried Na 2 CO 3 (0.11g, 1mmol) and trifluoromethanesulfonamide (TfNH 2 ) (2.98g, 20mmol) into a single-necked bottle, under nitrogen protection, the temperature of the oil bath was raised to about 120°C under stirring, and detected by TLC. When the epoxy compound disappeared, the reaction temperature was lowered to room temperature, and 100mL di Chloromethane, stirred for about 5 minutes and then filtered. The solution was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain 2.5 g of the compound of structural formula 2 (yield: 74%, ee: 99.2%).

[0030] 2. Deprotection to prepare the compound of structural formula 3

[0031] Add liquid ammonia (200mL) to THF (100mL) frozen to -40°C, a...

Embodiment 2

[0035] 1, the preparation of the compound of structural formula 2

[0036] With cis-epoxy compound 1 (89g, 0.5mol, methyl ester), Na 2 CO 3 (5.3g, 50mmol) and trifluoromethanesulfonamide (TfNH 2 ) (149g, 1.0mmol) was added to a dry three-necked flask, mechanically stirred at 500rpm, and placed on an oil bath under nitrogen protection, and the oil bath was heated to about 120°C under stirring, and detected by TLC until the epoxy compound Disappeared, removed the oil bath, lowered the reaction temperature to room temperature, added 4L of dichloromethane to the reaction flask, stirred for about 15 minutes, filtered, took the solution and concentrated it under reduced pressure to obtain a crude product, purified by silica gel column chromatography to obtain 117.8g of the compound of structural formula 2 (Yield: 72%, ee: 99%).

[0037] 2. Deprotection to prepare the compound of structural formula 3

[0038] Add liquid ammonia (1.5L) into THF (1L) frozen to -40°C, add sodium chi...

Embodiment 3

[0042] 1, the preparation of the compound of structural formula 2

[0043] Get a dry single-necked round bottom flask and place it on the oil bath, cis-epoxy compound 1 (1.78g, 10mmol, methyl ester), low-pressure freeze-dried Na 2 CO 3 (0.11g, 1mmol) and trifluoromethanesulfonamide (TfNH 2 ) (2.98g, 20mmol) was added to a single-necked bottle, under nitrogen protection, the oil bath was heated to about 90°C under stirring, and detected by TLC. The epoxy compound disappeared after a reaction time of about 10 hours, and the reaction temperature was lowered to room temperature. Add 100 mL of dichloromethane, stir for about 5 minutes and then filter. The solution is concentrated under reduced pressure to obtain a crude product, which is purified by silica gel column chromatography to obtain 1.7 g of the compound of structural formula 2 (yield: 51%, ee: 96.5%).

[0044] 2. Deprotection to prepare the compound of structural formula 3

[0045] Add liquid ammonia (200mL) to THF (10...

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Abstract

The invention discloses a method for synthesizing taxol side chains, which comprises the concrete steps: 1. preparing compounds with the structural formula 2; 2. preparing compounds with the structural formula 3 through protecting group removal; and 3. preparing compounds with the structural formula 4 through acylation reaction. The method disclosed by the invention utilizes the asymmetric ring opening of cis epoxy compounds to generate chiral centers, the dismounting is not needed, and the requirement can be reached only through removing a small quantity of isomers by silica gel column chromatography, so the operation is simplified, and the loss of a large amount of the isomers is reduced. Thereby, the compound yield is improved, in addition, products with high optical purity can be obtained, and the production cost of the side chains is greatly reduced. The method disclosed the invention has the concrete reaction formula shown in the accompanying drawing.

Description

technical field [0001] The invention relates to a method for synthesizing paclitaxel side chains. Background technique [0002] Paclitaxel has a very good effect in tumor treatment, but the natural extraction of paclitaxel is limited by various conditions, and it is expensive, so most of the world's paclitaxel turns to synthesis, but due to the complex structure of the mother nucleus, multifunctional groups, and multichirality center, etc., the total synthesis is extremely difficult, so now paclitaxel is mostly prepared by semi-synthesis, and the key to semi-synthesis is to obtain chiral side chains with high optical purity, so as to realize the combination with 10-deacetylbaccatin III (10-DABIII ) derivative docking. [0003] In the existing paclitaxel side chain synthesis patents, there are many ways to prepare by splitting, but the disadvantages are that the route is long, the yield after splitting is low, the operation is too cumbersome, and the investment in cost is to...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C233/87C07C231/02
CPCY02P20/55
Inventor 张伟中王权勇张爱平仝泽彬尹中船黄武蔡志香高卅
Owner SHANGHAI JINHE BIO TECH