A new biocatalysis method for the synthesis of 1- benzyl oct
As the skeleton structure of many bioactive natural products and drugs (such as the cough suppressant dexamethadine), moralane can be obtained from the key intermediate 1-benzyl octahydroisoquinoline derivatives by three-step chemical reaction.The synthesis methods of the intermediate include classical separation, asymmetric catalytic hydrogenation of transition metal and desematization of cyclohexamine oxidase and boramine, but these methods generally have disadvantages such as poor stereoselective, high production cost, poor atomic economy or serious environmental pollution.
Tianjin institute of industrial biotechnology, Chinese academy of sciences researcher Zhu Duiming, Wu Qia lead the biocatalysis and green chemical team, using Imine Reductase (Imine Reductase, IRED) antipodal selective reduction of a series of alpha, beta unsaturated Imine (1 - benzyl six hydrogen isoquinoline derivatives), the successful preparation of the corresponding 1 - benzyl eight hydrogen isoquinoline derivatives, for this class of compound synthesis provides an effective method of biological catalysis.
In this study, the imine reductase library was screened by using the precursor substrate of dextromethorphan, and it was found that two of the enzymes showed the highest and complementary stereoselective, with the enantiomer throughput up to 98% (S) and >.The catalytic efficiency was 5.4×10-2 and 24.1×10-2 s-1 mm-1, respectively.On this basis, a laboratory-scale preparation reaction was established, and the separation yield of the product was 74% and 80% respectively.Subsequently, an enzyme with higher spatial adaptability was obtained in the preparation of derivatives containing different substituents in the p-position and ortho-position of precursor substrates, which could obtain high stereoselectivity and separation yield for all eight substrates, and had significant competitive advantages over the existing synthesis methods of these compounds.
The research was supported by the national natural science foundation of China (21778072) and tianjin science and technology commission (15PTCYSY00020 and 15PTGCCX00060).The research was recently published in the journal Advanced catalysis & catalysis, and has been selected as the Hot Topic of bicatalysis.Yao peiyuan, an associate researcher at tianjin institute of technology, and xu zefei, a graduate student, are co-lead authors of the paper.
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