阅读说明：本技术 一种d-丝氨酸的制备方法 (Preparation method of D-serine ) 是由 陈艳辉 于 2019-11-13 设计创作，主要内容包括：本发明公开了一种D-丝氨酸的制备方法,涉及药物中间体制备领域,包括如下步骤：步骤一：L-丝氨酸水解；步骤二：DL-丝氨酸的制备；步骤三：D-丝氨酸的制备；步骤四：结晶处理；步骤五：干燥,测试包装,所述步骤一的具体工艺为,在15～45℃和pH7～9条件下,将0.15～0.6mol/L L-丝氨酸在催化剂催化下水解6-32h,反应完成后,抽滤,除去催化剂。本发明通过L-丝氨酸水解、DL-丝氨酸的制备、D-丝氨酸的制备、结晶处理、干燥,测试包装等工序,有效提高了制得的D-丝氨酸的光学纯度和收率,保证了D-丝氨酸的高光学活性,且工艺流程简单,大大的降低了工艺成本,适合进行大规模工业化生产,具有广阔的经济发展前景。(The invention discloses a preparation method of D-serine, relating to the field of preparation of drug intermediates and comprising the following steps: the method comprises the following steps: l-serine hydrolysis; step two: preparing DL-serine; step three: preparing D-serine; step four: crystallization treatment; step five: drying, testing and packaging, wherein the specific process in the first step is to hydrolyze 0.15-0.6 mol/L L-serine under the catalysis of a catalyst for 6-32h at 15-45 ℃ and at the pH of 7-9, and after the reaction is finished, performing suction filtration to remove the catalyst. According to the invention, through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like, the optical purity and yield of the prepared D-serine are effectively improved, the high optical activity of the D-serine is ensured, the process flow is simple, the process cost is greatly reduced, the method is suitable for large-scale industrial production, and the method has a wide economic development prospect.)

1. A preparation method of D-serine is characterized by comprising the following steps:

the method comprises the following steps: l-serine hydrolysis;

step two: preparing DL-serine;

step three: preparing D-serine;

step four: crystallization treatment;

step five: drying, testing and packaging.

2. The preparation method of D-serine according to claim 1, wherein the specific process of the first step is to hydrolyze 0.15-0.6 mol/L L-serine under the catalysis of a catalyst for 6-32h at 15-45 ℃ and pH 7-9, and after the reaction is completed, suction filtration is performed to remove the catalyst.

3. The process according to claim 1, wherein the step two comprises adding an amino acid racemase to the product obtained in the step one, followed by racemization to obtain DL-serine.

4. The method according to claim 1, wherein the step three comprises adding L-amino acid oxidase to the product DL-serine of the step two, and cleaving the mixture to obtain D-serine.

5. The method according to claim 1, wherein the step four comprises the specific step of injecting the concentrate from the step three into a crystallization tank, and heating the crystallization tank to crystallize the D-serine.

6. The method for preparing D-serine according to claim 1, wherein the specific process of the fifth step is that the wet sample obtained in the fourth step is placed into a dryer for drying, then a sampling test is carried out, and after the test is passed, a qualified product is packaged.

7. The method according to claim 1, wherein the mass ratio of the catalyst to the L-serine is 1: 3 to 10.

8. The process according to claim 1, wherein the crystallization time in step four is 15-50 min.

9. The method as claimed in claim 1, wherein the temperature of the crystallization tank in the fourth step is increased to 110-200 ℃.

10. The method as claimed in claim 1, wherein the drying time in the step five is 10-60min, and the drying temperature in the step five is 100-170 ℃.

Technical Field

The invention relates to the field of preparation of drug intermediates, in particular to a preparation method of D-serine.

Background

D-serine is an endogenous brain information synergic substance, can be used for preventing or treating brain injury caused by cerebral ischemia or anoxia, D-serine is also an important intermediate of some chiral drugs such as cycloserine, lacosamide and the like, a 25-peptide corticotropin analogue artificially synthesized by D-serine has 6 times stronger action than natural corticotropin and corticotropin 24 peptide and longer maintenance time, intravenous injection can last for 8 hours, is used for treating inflammatory patients such as temporal arteritis, multiple rheumatism and the like, and can also be used for biochemical research, preparation of tissue culture medium, reaction by taking DL-serine and chloroacetyl chloride as raw materials under alkaline condition, extraction by ethyl acetate after reduced pressure evaporation, and products are obtained after activated carbon treatment and acylase resolution, the optical purity and the yield in the preparation process of D-serine in the prior art are lower, and the high optical activity of the D-serine is difficult to ensure, the process flow is complex, the production process cost is high, and the method is not suitable for large-scale industrial production.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides a preparation method of D-serine.

In order to achieve the purpose, the invention adopts the following technical scheme:

a preparation method of D-serine comprises the following steps:

the method comprises the following steps: l-serine hydrolysis;

step two: preparing DL-serine;

step three: preparing D-serine;

step four: crystallization treatment;

step five: drying, testing and packaging.

Preferably, the specific process of the first step is that 0.15-0.6 mol/L L-serine is hydrolyzed under the catalysis of a catalyst for 6-32 hours at 15-45 ℃ and at the pH of 7-9, and after the reaction is finished, the catalyst is removed by suction filtration.

Preferably, the specific process of the second step is to add amino acid racemase to the product of the first step, and obtain DL-serine through racemization.

Preferably, the specific process of the third step is to add L-amino acid oxidase to the product DL-serine in the second step, and obtain D-serine through splitting.

Preferably, the specific process of the step four is to inject the concentrated solution in the step three into a crystallization tank, heat the temperature of the crystallization tank, and crystallize.

Preferably, the specific process of the fifth step is that the wet sample in the fourth step is put into a dryer for drying, then a sampling test is carried out, and after the test is qualified, a qualified product is packaged.

Preferably, the mass ratio of the catalyst to the L-serine is 1: 3 to 10.

Preferably, the crystallization time in the fourth step is 15-50 min.

Preferably, the temperature of the crystallization tank in the fourth step is heated to 110-200 ℃.

Preferably, the drying time in the step five is 10-60min, and the drying temperature in the step five is 100-170 ℃.

The invention has the beneficial effects that:

according to the invention, through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like, the optical purity and yield of the prepared D-serine are effectively improved, the high optical activity of the D-serine is ensured, the process flow is simple, the process cost is greatly reduced, the method is suitable for large-scale industrial production, and the method has a wide economic development prospect.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.