阅读说明：本技术 一种4-硫代核苷类化合物提纯方法 (Method for purifying 4-thionucleoside compound ) 是由 李德鹏 王玉婷 张晓辉 于 2020-07-27 设计创作，主要内容包括：本发明属于化学化工技术领域,公开了一种4-硫代核苷类化合物提纯方法。4-硫代核苷粗产物先经过柱层析分离法分离后,得到分离产物,将得到的分离产物进行提纯,提纯步骤为：先溶解于极性小的溶剂中,再将其放置在冷却环境即0℃以下、10-30分钟后再加入极性大的溶剂混合搅拌后；在0.1MPa以下,50℃-70℃条件下进行减压旋蒸,旋蒸后得到提纯固体产物。本发明提供一种4-硫代核苷类化合物提纯方法,可以替代重结晶法,可以使产品的产率大大提高,该方法操作简便,适用范围广。(The invention belongs to the technical field of chemistry and chemical engineering, and discloses a method for purifying a 4-thio nucleoside compound. Separating the crude 4-thionucleoside product by column chromatography to obtain a separated product, and purifying the separated product, wherein the purification steps are as follows: dissolving in solvent with small polarity, placing in cooling environment at 0 deg.C below for 10-30 min, adding solvent with large polarity, mixing and stirring; performing reduced pressure rotary evaporation at 50-70 deg.C under 0.1MPa to obtain purified solid product. The invention provides a method for purifying 4-thionucleoside compounds, which can replace a recrystallization method, greatly improve the yield of products, and has simple and convenient operation and wide application range.)

1. A method for purifying 4-thio nucleoside compounds is characterized in that a crude 4-thio nucleoside product is separated by a column chromatography separation method to obtain a separation product, the obtained separation product is purified, and the purification steps are as follows: dissolving in solvent with small polarity, placing in cooling environment at 0 deg.C below for 10-30 min, adding solvent with large polarity, mixing and stirring; performing reduced pressure rotary evaporation at 50-70 deg.C under 0.1MPa to obtain purified solid product.

2. The method of claim 1, wherein the purification of 4-thionucleosides is carried out by subjecting the nucleoside derivative to a purification step,

the preparation conditions of the crude 4-thionucleoside product are as follows:

introducing ammonia methanol solution into the 4-sulfur-2 ',3',5' -O-triacetyl nucleoside compound, fully stirring at room temperature, monitoring the reaction by TCL, completely reacting for 4-7 hours, and distilling off the solvent under the reduced pressure of 40-50 ℃ to obtain a crude product of the 4-sulfur nucleoside.

3. The method of claim 2, wherein the purification of 4-thionucleoside compounds,

the column chromatography separation conditions are as follows: the crude 4-thiocucleoside product was isolated by column chromatography (CHCl)₂:CH₃OH 15-30:1) to obtain the viscous 4-thionucleoside compound.

4. The method of claim 3, wherein the purification of 4-thionucleoside compounds,

the solvent with low polarity is CHCl₂。

5. The method of claim 4, wherein the highly polar solvent is CH₃OH。

6. The method for purifying 4-thionucleoside compounds as claimed in claim 5, wherein the purification step comprises: dissolving the separated viscous 4-sulfur nucleoside compound in CHCl solvent₂Placing in a cooling environment, i.e. below 0 deg.C for 10-30 min, adding CH₃OH is mixed and stirred, and then is subjected to reduced pressure rotary evaporation at the temperature of 50-70 ℃ under reduced pressure, and a purified solid product, namely the 4-thionucleoside compound is obtained after the rotary evaporation.

Technical Field

The invention belongs to the technical field of chemistry and chemical engineering, and relates to a method for purifying 4-thionucleoside.

Background

It is known that the death rate caused by cancer is higher and higher, and the main reason for causing cancer is that DNA damage can not be repaired, and the current methods for treating cancer include radiotherapy, chemotherapy and surgical treatment, which all have the defects that the methods can bring side effects to human bodies, and the photodynamic therapy is developed later, and the method uses photosensitive substances to react with cancer cells under the irradiation of light with certain wavelength to achieve the effect of treating the cancer cells.

According to a great amount of researches at present, the nucleoside compounds modified by glycosyl and base show good antitumor activity, and the 4-thionucleoside analogues can play a role in treating cancers under the assistance of ultraviolet light due to unique chemical and physical properties, and have the characteristics of good selectivity and low toxicity, and the low energy of UVA ensures that the conditions for killing cells are mild, has potential selectivity and has no harm to human cells. And 4-sulfur nucleoside analogues are widely applied to clinical aspects as antiviral and antitumor drugs at present. The 4-thionucleoside analogue has wide application prospect.

In the method for synthesizing the 4-thionucleoside compound, the purity and the yield of the final product are influenced due to the use of the final separation and purification method, and the methods used for separating and purifying the product are column chromatography separation and recrystallization, so that the yield of the obtained product is not high.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a method for purifying 4-thionucleoside compounds, which can replace a recrystallization method, greatly improve the yield of products, and has simple and convenient operation and wide application range.

The above purpose of the invention is realized by the following technical scheme:

a4-thio nucleoside compound purification method, after the crude product of 4-thio nucleoside is separated by column chromatography separation method, the separation product is obtained, the separation product obtained is purified, the purification steps are: dissolving in solvent with small polarity, placing in cooling environment at 0 deg.C below for 10-30 min, adding solvent with large polarity, mixing and stirring; performing reduced pressure rotary evaporation at 50-70 deg.C under 0.1MPa to obtain purified solid product.

The purity of the solvent is analytically pure,

the preparation conditions of the crude 4-thionucleoside product are as follows:

introducing an ammonia methanol solution into the 4-sulfur-2 ',3',5' -O-triacetyl nucleoside compound, fully stirring at room temperature, monitoring the reaction by TCL, completely reacting for 4-7 hours, and evaporating the solvent under the reduced pressure of 40-50 ℃ to obtain a 4-sulfur nucleoside crude product;

the column chromatography separation conditions are as follows: the crude 4-thiocucleoside product was isolated by column chromatography (CHCl)₂:CH₃OH 15-30:1) to obtain a viscous 4-thionucleoside compound as a separation product;

the solvent with low polarity is CHCl₂；

The solvent with high polarity is CH₃OH；

The purification steps are specifically as follows: dissolving the separated viscous 4-sulfur nucleoside compound in CHCl solvent₂Placing in a cooling environment, i.e. below 0 deg.C for 10-30 min, adding CH₃OH is mixed and stirred, and then is subjected to reduced pressure rotary evaporation at the temperature of 50-70 ℃ under reduced pressure, and a purified solid product, namely the 4-thionucleoside compound is obtained after the rotary evaporation.

Compared with the prior art, the invention has the beneficial effects that:

the existing purification method adopts a recrystallization method for purification, and the extracted product has low purity, low purification yield and yield reaching 50 percent; the purification method of the 4-thionucleoside compound provided by the invention can replace a recrystallization method, high-temperature heating is not needed, and the recrystallization method is simple, convenient and quick to operate. Secondly, the purification method of the 4-thionucleoside compound provided by the invention can improve the yield of the product and improve the purity of the product. Provides a new idea for the separation and purification of products, can be applied to the purification method of various products, and has important significance.

Drawings

FIG. 1 is a hydrogen nuclear magnetic spectrum of 4-thiouridine, a pale yellow solid obtained in example 1.

FIG. 2 is a carbon nuclear magnetic spectrum of 4-thiouridine, a pale yellow solid obtained in example 1.

FIG. 3 is a hydrogen nuclear magnetic spectrum of 4-thiothymidine as a pale yellow solid obtained in example 2.

FIG. 4 is a carbon nuclear magnetic spectrum of 4-thiothymidine as a pale yellow solid obtained in example 2.

Detailed Description

The invention is described in more detail below with reference to specific examples, without limiting the scope of the invention. Unless otherwise specified, the experimental methods adopted by the invention are all conventional methods, and experimental equipment, materials, reagents and the like used in the experimental method can be obtained from commercial sources.