Preparation method of quininone reductase RrQR, and application of quininone reductase RrQR in preparation of (R)-3-quinuclidinol

Abstract

The invention discloses a preparation method of quininone reductase RrQR, and applications of the quininone reductase RrQR. The applications of the quininone reductase RrQR comprise: an application of the RrQR as quininone reductase; an application of biomaterials related with the RrQR in the preparation of quininone reductase; an application of the RrQR in synthesis of R-3-quinuclidinol; and an application of the biomaterials related with the RrQR in the synthesis of the R-3-quinuclidinol. Experiments prove that the quininone reductase RrQR has high specific vitality and thermal stability and can asymmetrically reduce 3-quininone into optically active R-3-quinuclidinol.

Description

technical field [0001] The invention relates to a preparation method and application of a quinine reductase RrQR in the field of biotechnology. Background technique [0002] R-3-quinine alcohol is an important intermediate of many anticholinergic drugs, such as solifenacin, ravatorate, etc. are the latest anticholinergic drugs containing R-3-quinine alcohol structure, for the treatment of urinary incontinence and chronic obstruction Pulmonary disease (COPD) has a very good effect. There are two kinds of synthesis of R-3-quinine alcohol, chemical method and biological method. The chemical synthesis of R-3-quinine alcohol will leave metal catalysts in the product. Compared with the chemical method, the biological method has many advantages such as mild reaction conditions, high conversion rate, and strong stereoselectivity. Therefore, the biological method is developed to The synthesis of R-3-quinine alcohol is the direction of industrial production. [0003] The use of qui...

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Problems solved by technology

After 1.5 hours, 1M quinine was completely converted into R)-3-quinine alcohol, and the enantiomeric excess value (ee) was greater than 99% (patent application number: 201310422722.1); Xu Jianhe and others screened out The specific activity of quinine ketone reductase is 198U / mg, but its thermal stability is not good enough (ORGANIC LETTERS 2013Vol.15, No.194917–4919). Quinone reductase is an urgently needed technology for the production of R-3-quinine alcohol by reductase method

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