Preparation method of 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose

An acetyl and ribose technology, applied in the preparation of sugar derivatives, chemical instruments and methods, sugar derivatives, etc., can solve the problems of many by-products, low purity, long operation time, etc., and achieve simple and moderate conditions and high yield. Effect

Active Publication Date: 2010-09-08
SUQIAN KEYLAB BIOCHEMICAL CO LTD
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  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this method is: the cost of iodine/imidazole/triphenylphosphine system is high, and the acetylation temperature is high, there are many by-products, and it is difficult to crystallize
The disadvantage of this step is: (1) This step uses a large amount of pyridine or triethylamine, which is extremely harmful to the environment
(2) Since it takes a lot of time and energy to remove water in the reaction system when using acetic anhydride
[0007] The ratio of β:α isomers in the 1,2,3-tri-O-acetyl-5-deoxy-D-ribose finall

Method used

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  • Preparation method of 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1）

[0026] The method of the present embodiment has the following steps:

[0027] ①Add 50.3g of 2,3-O-isopropylidene-5-deoxy-D-furanoside to 300mL of 1wt% hydrochloric acid solution, and 2,3-O-isopropylidene Propylene-5-deoxy-D-furanoside undergoes a hydrolysis reaction of 5-deoxy-D-ribose for 4 hours, and TLC (thin layer chromatography) monitors until the raw material point disappears (dichloromethane:methanol=1:1), After the reaction, 297.3 g of an aqueous solution containing 5-deoxy-D-ribose was obtained.

[0028] ② Add 303.0 g of acetylation reagent vinyl acetate to the aqueous solution containing 5-deoxy-D-ribose obtained in step ①, and generate 1,2,3-tri-O-acetyl at a temperature of 15°C to 25°C The acetylation reaction of base-5-deoxy-D-ribose was carried out for 3 hours. During the reaction, 5% NaOH solution was added dropwise to keep the pH at 10. An aqueous solution containing 1,2,3-tri-O-acetyl-5-deoxy-D-ribose was obtained.

[0029]③ After the acetylation reaction, ...

Embodiment 2）

[0034] The method of the present embodiment has the following steps:

[0035] ①Add 51.2g of 2,3-O-isopropylidene-5-deoxy-D-furanoside to 250mL of sulfuric acid solution with a concentration of 1wt%. Propylene-5-deoxy-D-methylfuranoside undergoes a hydrolysis reaction of 5-deoxy-D-ribose for 3 hours, and TLC monitors until the raw material point disappears (dichloromethane:methanol=1:1). After the reaction, the obtained 237.2 g of an aqueous solution containing 5-deoxy-D-ribose.

[0036] ② Add 242.2 g of acetylation reagent vinyl acetate to the aqueous solution containing 5-deoxy-D-ribose obtained in step ①, and generate 1,2,3-tri-O-acetyl at a temperature of 15°C to 25°C The acetylation reaction of base-5-deoxy-D-ribose was 4h, and the concentration of 10% Na was added dropwise during the reaction 3 PO 4 solution to maintain a pH of 10. An aqueous solution containing 1,2,3-tri-O-acetyl-5-deoxy-D-ribose was obtained.

[0037] ③ After the acetylation reaction, carry out pos...

Embodiment 3）

[0042] The method of the present embodiment has the following steps:

[0043] ①Add 50.4g of 2,3-O-isopropylidene-5-deoxy-D-furanoside to 250mL of sulfuric acid solution with a concentration of 1wt%. Propylene-5-deoxy-D-methylfuranoside undergoes a hydrolysis reaction of 5-deoxy-D-ribose for 3 hours, and TLC monitors until the raw material point disappears (dichloromethane:methanol=1:1). After the reaction, the obtained 230.3 g of an aqueous solution containing 5-deoxy-D-ribose.

[0044] ② Add 232.1 g of acetylation reagent isopropenyl acetate to the aqueous solution containing 5-deoxy-D-ribose obtained in step ①, and generate 1,2,3-tri-O- The acetylation reaction of acetyl-5-deoxy-D-ribose was 3h, and the concentration of 10% Na was added dropwise during the reaction 2 CO 3 solution to maintain a pH of 10. An aqueous solution containing 1,2,3-tri-O-acetyl-5-deoxy-D-ribose was obtained.

[0045] ③ After the acetylation reaction, carry out post-treatment to obtain the crude...

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Abstract

The invention discloses a preparation method of 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose. The preparation method comprises the following steps of: (1) carrying out a hydrolysis reaction on 2,3-O-isopropylidene-5-deoxidization-D-furan glucoside and aqueous acid; (2) adding an acetylation reagent to the aqueous solution obtained in the step (1) to carry out an acetylation reaction, wherein the acetylation reagent is vinyl acetate or isopropenyl acetate; (3) post-treating the aqueous solution obtained in the step (2) to obtain a crude 1,2,3-tri-O-acetyl-5-deoxidization-D-ribose product; and (4) separating the crude product to obtain the 1,2,3-tri-O-acetyl-5-deoxidization-beta-D-ribose the purity of which is not lower than 99.5 percent. In the invention, the vinyl acetate or the isopropenyl acetate is adopted to directly carry out the acetylation reaction with 5-deoxidization-D-ribose in the aqueous solution, and the 1,2,3-tri-O-acetyl-5-deoxidization-D-ribose with higher beta isomer purity is finally obtained.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose. Background technique [0002] Capecitabine (trade name Xeloda) is a nucleoside anticancer drug mainly used in the treatment of breast and rectal cancer. U.S. Patent Document US5453497A discloses a method of condensing 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose with 5-fluorocytosine, then acylation, and finally hydrolysis to obtain The method of capecitabine. [0003] There are several methods for preparing 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose: [0004] Chinese patent document CN101012252 (Application No.: 200710019873.7) discloses a method that uses inosine as a raw material, first performs iodination reaction with iodine, then performs liquid-phase hydrogenation with hydrogen, then performs acetylation reaction with acetic anhydride, and finally breaks the bond Deglycosides give 1,2,3-tri-O-acet...

Claims

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Application Information

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IPC IPC(8): C07H13/06C07H1/00
Inventor 李庆毅张寅孙海江
Owner SUQIAN KEYLAB BIOCHEMICAL CO LTD
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