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Analysis on the Application of Enzyme Catalysis Technology in Green Chemistry

2020-12-17
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Green chemistry technology is an innovation to traditional chemistry. The green development of chemical synthetic drugs puts the protection of the environment first and avoids the discharge of harmful substances into the environment, which brings new challenges to traditional chemistry. At present, biotechnology represented by enzyme catalysts not only has good selectivity, but also has the characteristics of non-toxic and harmless, and has good development prospects. It has been widely used in the chemical production process.

Enzyme is an important catalyst in the organism, and it is a catalytic organic matter produced by living cells. Biochemical reaction technology can use enzymes as catalysts, and effectively use biomass as raw materials to achieve the production of compounds. It can not only alleviate the waste of non-renewable resources, but also reduce the pollution impact on the surrounding environment. The advantages of enzyme catalysis in environmental protection and efficiency have made it widely used in the fields of medicine, agriculture, food, chemical industry, environmental protection, etc., but at the same time, enzymes have defects such as instability, single substrate, and harsh reaction conditions.

chemistry technology

Enzyme catalyst catalysis has the characteristics of mild reaction conditions, high regioselectivity and high stereoselectivity. With the rise of science and technology and green chemistry technology, enzyme catalysis technology has been highly valued as an important branch of green chemistry. Medicilon has been vigorously developing new technologies in recent years, integrating new green chemistry methods into customer services, and using current popular green enzyme chemistry, photo-redox catalysts, continuous reactions, etc., to provide the company with high-quality economic solutions Program.

In the current research and development of chemically synthesized drugs, biocatalytic processes have been able to improve certain chemical synthesis processes, such as the synthesis of chiral amines, the spatial and regional hydroxylation of complex molecules, and certain redox reactions. The use of enzyme catalysis technology can convert precursor substances into compound building blocks, and can also generate required optical enantiomeric compounds with special pharmacological effects. Combining directed evolution technology with chemical synthesis methods can use enzymes to generate pharmaceutical intermediates and then synthesize them into bulk drugs.

Enzyme catalysis technology is widely used in the pharmaceutical industry. For example, the enzymatic preparation of anti-diabetic compound sitagliptin reported on the Internet is one of the more successful examples of biocatalytic processes in the pharmaceutical industry. Sitagliptin is a drug for the treatment of type II diabetes. Researchers from Codexis and Merck have constructed two R-type aminotransferases R-ATA and ATA-117 from Arthrobacter sp. for the first time, and used sitagliptin precursors. Ketones are used as substrates for asymmetric amination reactions. Since the substrate is a large hindered compound, the catalytic activity of wild-type transaminase is extremely low. The use of genome walking, homology modeling and site-directed mutagenesis technology can significantly improve the catalytic activity of transaminase for large steric substrates. After further optimizing the reaction process, under the conditions of 1mol/L i-PrNH2, 40, using 50% DMSO as a co-solvent, 200g/L sitagliptin precursor ketone can be completely converted, and the product ee>99.95%. Compared with the rhodium catalytic process, the biocatalytic process not only reduces the waste of substrates and eliminates the demand for rare heavy metals (Rh), but also increases the total yield by 10%, and the final yield [kg/(L • d)] An increase of 53%. In addition, there have been reports of the use of R-type or S-type transaminase for large-scale drug synthesis, such as niraparib and Janus kinase 2 (JAK2) inhibitors.

In recent years, the chemical structure of pharmaceuticals has become more and more complex, and the environmental requirements for green synthesis technologies are also increasing. Seeking low-cost, safer and more environmentally friendly biocatalytic processes to upgrade traditional chemical processes is the goal of the pharmaceutical industry. With the development of protein engineering technology, it is believed that biocatalysts have more room for improvement, which can be more popularized in the pharmaceutical industry and continue to benefit the global green cause.

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