Continuous flow manufacture is an innovative technology platform, which is gaining momentum within the pharmaceutical industry. The key advantages of continuous flow include faster and safer reactions, which can be more environmentally friendly, smaller footprint, better quality product, and critically, the ability to perform chemistry that is difficult or impossible to do in batch mode. Globally, significant efforts have been made to develop the manufacturing flexibility and robustness of processes used to produce chemicals in a continuous way, yet despite these scientific developments, a major challenge for industry is the established application of flow technology to commercially relevant examples. The identification of opportunities to apply flow solutions to current processes is also critical to the success of this new technology for pharmaceutical and fine chemical companies. This review highlights industrial hurdles and the importance of education and showcases recent (2018−2019) and relevant industrial examples where utilization of flow technology has been successfully performed.
Chiral amines are valuable building blocks for the pharmaceutical industry. ω-TAms have emerged as an exciting option for their synthesis, offering a potential "green alternative" to overcome the drawbacks associated with conventional chemical methods. In this review, we explore the application of ω-TAms for pharmaceutical production. We discuss the diverse array of reactions available involving ω-TAms and process considerations of their use in both kinetic resolution and asymmetric synthesis. With the aid of specific drug intermediates and APIs, we chart the development of ω-TAms using protein engineering and their contribution to elegant one-pot cascades with other enzymes, including carbonyl reductases (CREDs), hydrolases and monoamine oxidases (MAOs), providing a comprehensive overview of their uses, beginning with initial applications through to the present day.
Continuous flow chemistry is often viewed as a very simple concept on paper, however scientists with significant flow chemistry experience will highlight a number of challenges that need to be overcome. Critical for the successful development of any flow process is a high level of understanding of potential pitfalls that may be encountered. A collaborative and multi‐disciplinary team of chemists and chemical engineers is essential in the development of a process from lab scale through to production. This Minireview will identify and highlight relevant risks and their subsequent mitigation strategies to ensure successful flow processing.
In the pursuit of robust and reusable biocatalysts for industrial synthetic chemistry, nanobiotechnology is currently taking a significant part. Recently, enzymes have been immobilized on different nanoscaffold supports. Carbon coated metallic nanoparticles were found to be a practically useful support for enzyme immobilization due to their large surface area, high magnetic saturation, and manipulatable surface chemistry. In this study carbon coated cobalt nanoparticles were chemically functionalized (diazonium chemistry), activated for bioconjugation (N,N-disuccinimidyl carbonate), and subsequently used in enzyme immobilization. Three enzymes, β-glucosidase, α-chymotrypsin, and lipase B were successfully covalently immobilized on the magnetic nonsupport. The enzyme-particle conjugates formed retained their activity and stability after immobilization and were efficiently recycled from milliliter to liter scales in short recycle times.
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