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Method for producing (S)-3-chlorobenzene phenylpropanol through carbonyl reductase catalysis

A technology of chlorophenylpropanol and reductase, which is applied in the direction of fermentation, etc., can solve the problems that cannot meet the needs of industrial production, and achieve the effect of reducing production costs

Inactive Publication Date: 2018-07-31
ZHEJIANG OCEAN UNIV
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Problems solved by technology

The biological preparation of (S)-3-chlorophenylpropanol has been reported at present, the chiral ee value is greater than 99, and the conversion efficiency is greater than 99, but its maximum substrate concentration is only 16.86 g / L ( J Mol Catal B-Enzym 2011,70: 114-118), far from meeting the needs of industrial production

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Embodiment Construction

[0011] The present invention will be described in detail below in conjunction with specific examples: A kind of method of utilizing carbonyl reductase to catalyze the production of (S)-3-chlorophenylpropanol according to the present invention, the described method comprises the steps of: utilizing existing Some carbonyl reductases are used as catalysts to catalyze the substrate 3-chloropropiophenone to produce (S)-fluoxetine intermediate (S)-3-chloropropiophenone with high chiral ee value (ee>99) .

[0012] As a preferred embodiment: the carbonyl reductase ChKRED20 is used as a catalyst, wherein the reaction system is: pH=6.0-8.0, 0.1M potassium phosphate buffer, carbonyl reductase ChKRED20, NADH (reduced coenzyme I) or NADPH ( Reduced coenzyme II) and substrates.

[0013] As a further preferred embodiment: the substrate concentration in the reaction solution of the present invention is 5-100mM, and the concentration of NADH or NADPH is greater than or equal to the molar conc...

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Abstract

The invention discloses a method for producing (S)-3-chlorobenzene phenylpropanol through carbonyl reductase catalysis. The method is characterized by comprises the following steps: utilizing existingcarbonyl reductase as a catalyst; performing catalytic production on a substrate 3-chlorobenzene phenylpropanol to produce high-chirality ee (larger than 99) value (S)-fluoxetine intermediate (S)-3-chlorobenzene phenylpropanol; utilizing carbonyl reductase ChKRED20 as a catalyst, wherein a reaction system comprises a pH equal to 6.0 to 8.0, a 0.1M potassium phosphate buffer solution, the carbonylreductase ChKRED20, NADH (reduced coenzyme I) or NADPH (reduced coenzyme II) and the substrate. According to the method disclosed by the invention, a biological-enzyme catalytic method is utilized for preparing the high-chirality ee (larger than 99) value (S)-fluoxetine intermediate (S)-3-chlorobenzene phenylpropanol, a traditional chemical synthesizing method is replaced, and production cost andenvironmental pollution are reduced.

Description

technical field [0001] The invention relates to a method for catalyzing the production of (S)-3-chlorophenylpropanol by using carbonyl reductase, and belongs to the technical field of biocatalysis. Background technique [0002] Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI), which is suitable for the treatment of various depressive disorders, including mild or severe depression, depression of bipolar affective disorder, psychogenic Sexual depression and depressive neurosis. Its mechanism of action is to inhibit the uptake of 5-hydroxytryptamine from the synaptic cleft by neurons and increase the available neurotransmitter in the gap, thereby improving the emotional state and treating depressive mental disorders. [0003] (S)-3-Chlorophenylpropanol is an important intermediate in the chemical synthesis of (S)-fluoxetine. The biological preparation of (S)-3-chlorophenylpropanol has been reported at present, the chiral ee value is greater than 99,...

Claims

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Application Information

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IPC IPC(8): C12P7/22
CPCC12P7/22
Inventor 唐云平周亚锋陈艳余方苗杨最素黄芳芳丁国芳
Owner ZHEJIANG OCEAN UNIV
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