A brief analysis of the application of enzyme-catalyzed techniques in green chemistry

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Green chemistry technology represents an innovation in traditional chemistry. The development of green methods for the chemical synthesis of drugs gives priority to environmental protection by preventing the release of harmful substances into the environment, thus posing new challenges to conventional chemistry. Currently, biotechnology, represented by enzyme catalysts, not only possesses excellent selectivity but is also non-toxic and harmless, offering great prospects for development. It has already been widely applied in chemical production processes. Enzymes are important catalysts in living organisms; they are organic substances with catalytic properties that are produced by living cells. Biochemical reaction technology can utilize enzymes as catalysts and effectively employ biomass as a raw material to produce compounds. It not only helps to significantly reduce the waste of non-renewable resources but also greatly lowers the environmental pollution it causes in the surrounding area. The advantages of enzyme catalysis in terms of environmental protection and efficiency have led to its widespread use in fields such as medicine, agriculture, food processing, the chemical industry, and environmental protection. However, enzymes also have drawbacks such as instability, limited substrate specificity, and demanding reaction conditions. Enzyme catalysts exhibit the characteristics of mild reaction conditions, as well as high regioselectivity and stereoselectivity. With the advancement of science and technology as well as green chemistry techniques, enzyme catalysis has received considerable attention as an important branch of green chemistry. Over the years, Medici has made significant efforts to develop new technologies, integrating emerging approaches from green chemistry into its services for customers. By utilizing current trends such as green enzyme chemistry, photooxidoredox catalysts, and continuous flow reactions, the company is able to provide high-quality and cost-effective solutions. In the development of chemically synthesized drugs, biocatalytic processes are now able to improve certain chemical synthesis methods, such as the synthesis of chiral amines, the spatial and regioselective hydroxylation of complex molecules, and certain redox reactions. Enzyme-catalyzed techniques can be used to convert precursor substances into compound building blocks, as well as to produce the desired optically enantiomeric compounds with specific pharmacological effects. By combining directed evolution techniques with chemical synthesis methods, enzymes can be used to produce pharmaceutical intermediates, which can then be synthesized into active pharmaceutical ingredients. Enzyme catalysis is widely used in the pharmaceutical industry; for example, the enzymatic synthesis of the anti-diabetic compound sitagliptin, as reported in online sources, is one of the successful applications of biocatalytic processes in the pharmaceutical industry. Sitagliptin is a drug used to treat type 2 diabetes. Researchers at Code*s and Merck were the first to isolate two strains of R-type transaminases, R-ATA and ATA-117, from Arthrobacter sp., and used sitagliptin precursors as substrates for asymmetric amination reactions. Since the substrate is a highly sterically hindered compound, the catalytic activity of the wild-type transaminase is extremely low. The use of genomic shuffling, homology modeling combined with site-directed mutagenesis can significantly enhance the catalytic activity of transaminases toward highly sterically hindered substrates. After further optimization of the reaction process, under conditions of 1 mol/L i-PrNH2 and 40°C, with 50% DMSO used as a cosolvent, the 200 g/L sitagliptin precursor can be completely converted, yielding a product with an ee > 99.95%. Compared to the rhodium-catalyzed process, the biocatalytic process not only reduces substrate waste and eliminates the need for rare heavy metals (Rh), but also increases the overall yield by 10%, resulting in a 53% increase in the final yield. Furthermore, there have been reports on the use of R-type or S-type transaminases for large-scale drug synthesis, such as niraparib and Janus kinase 2 (JAK2) inhibitors. In recent years, the chemical structures of drugs have become increasingly complex, and the demands on green synthesis technologies from the environment are also rising. The pharmaceutical industry is constantly striving to find low-cost, safer, and more environmentally friendly biocatalytic processes to improve traditional chemical processes. With the advancement of protein engineering technology, it is believed that biocatalysts have even greater potential for improvement, enabling their wider use in the pharmaceutical industry and continuing to contribute to global green initiatives.