Preparation method for simvastatin by adopting enzymatic synthesis

A technology for simvastatin and enzymatic synthesis, which is applied in the field of preparation of simvastatin by enzymatic synthesis, can solve the problems of difficult acquisition, many reaction steps, and many by-products, and achieve the reduction of the number and content of impurities and the production process Ease of operation and reduction of reaction steps

Active Publication Date: 2014-04-16
福安药业集团烟台只楚药业有限公司
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  • Application Information

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Problems solved by technology

The existing simvastatin production process, such as CN1290261A, CN1612872A, CN1493570A, etc., is mainly a chemical synthesis method, not only has many and complicated reaction steps, but also has high impurities in the product, and the process has serious environmental pollution
CN102703539A discloses a method for preparing simvastatin from lovastatin through a process comprising enzymatic hydrolysis and enzymatic acylation and the enzymes

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The preparation method of enzymatically synthesizing simvastatin comprises the following steps:

[0027] 1) Add lovastatin into a stainless steel reaction tank, add purified water and sodium hydroxide at the same time, start stirring, raise the temperature to 60°C for 30 minutes, add the amount of purified water equal to the weight of lovastatin, add the amount of sodium hydroxide It is 1 / 15 of the weight of lovastatin;

[0028] 2) Take a sample of the mixed solution obtained in step 1), and detect the residue of lovastatin. When the residue of lovastatin is less than 0.5%, proceed to the next step;

[0029] 3) Cool down the solution obtained in step 2) to 30°C;

[0030] 4) Add 20mM NH4 / NH4CL to the solution obtained in step 3), adjust the pH to 8.9-9.1, and raise the temperature to 35°C;

[0031] 5) Add the filtrate obtained in step 4) to lovastatin immobilized hydrolase (purchased from CSPC), and the amount of immobilized hydrolase is equal to the weight of lovastat...

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PUM

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Abstract

The invention discloses a preparation method for simvastatin by adopting enzymatic synthesis. The method comprises the following steps: carrying out basic hydrolysis on lovastatin so as to obtain a alkaline hydrolysis product; carrying out enzyme hydrolysis on the prepared alkaline hydrolysis product under the existence of immobilized hydrolase so as to obtain enzymic hydrolysate and 2,2-dimethyl acyl-S-methyl propionate, wherein the immobilized hydrolase is a composite which is formed by immobilizing lovastatin hydrolase on porous resin; carrying out acylation reaction on the prepared enzymic hydrolysate and 2,2-dimethyl acyl-S-methyl propionate under the existence of immobilized acylase so as to obtain acylate, wherein the immobilized acylase is a composite which is formed by immobilizing lovastatin acylation enzyme on the porous resin; and carrying out cyclization on the prepared acylate so as to obtain the simvastatin. By adopting the the method disclosed by the invention, the total molar yield of the simvastatin achieves 80%, the content of total impurities in the simvastatin is smaller than or equal to 0.5%; the content of a single impurity in the simvastatin is smaller than or equal to 0.2%; the content of the lovastatin in the simvastatin is smaller than or equal to 0.2%. The technology is significantly better than an existing production technology of the simvastatin.

Description

technical field [0001] The invention relates to a method for synthesizing simvastatin, a blood lipid-lowering drug, in particular, it provides a method for preparing simvastatin by enzymatic synthesis. Belongs to the field of medicine. Background technique [0002] Simvastatin is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which is mainly used clinically to treat hypercholesterolemia and hypertriglyceridemia. The drug was first launched in Sweden in 1988, and has been widely used in more than 70 countries in 1995. In recent years, it has been found that in addition to blood lipid regulation, it also has other effects, such as anti-oxidation, anti-inflammation, inhibition of cell proliferation, promotion of bone anabolism, and treatment of heart failure. The existing simvastatin production process, such as CN1290261A, CN1612872A, CN1493570A, etc., is mainly a chemical synthesis method, not only has many and complicated reaction steps, but also has high...

Claims

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Application Information

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IPC IPC(8): C12P17/06
Inventor 葛祥斌李贤坤杨俊发马金凤张健
Owner 福安药业集团烟台只楚药业有限公司
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