Research Output
1 - 6 of 6
Publication
Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives
2021-02-04, Leslie, Alexander, Moody, Thomas S., Smyth, Megan, Wharry, Scott, Baumann, Marcus
A continuous flow process is presented that couples a Curtius rearrangement step with a biocatalytic impurity tagging strategy to produce a series of valuable Cbz-carbamate products. Immobilized CALB was exploited as a robust hydrolase to transform residual benzyl alcohol into easily separable benzyl butyrate. The resulting telescoped flow process was effectively applied across a series of acid substrates rendering the desired carbamate structures in high yield and purity. The derivatization of these products via complementary flow-based Michael addition reactions furthermore demonstrated the creation of β-amino acid species. This strategy thus highlights the applicability of this work towards the creation of important chemical building blocks for the pharmaceutical and speciality chemical industries.
Publication
Overcoming the Hurdles and Challenges Associated with Developing Continuous Industrial Processes
2020-12-31, Baumann, Marcus, Moody, Thomas S., Smyth, Megan, Wharry, Scott
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.
Publication
Tandem Continuous Flow Curtius Rearrangement and Subsequent Enzyme-Mediated Impurity Tagging
2021, Baumann, Marcus, Leslie, Alexander, Moody, Thomas S., Smyth, Megan, Wharry, Scott
The use of continuous flow as an enabling technology within the fine chemical and pharmaceutical industries continues to gain momentum. The associated safety benefits with flow for handling of hazardous or highly reactive intermediates are often exploited to offer industrially relevant and scalable Curtius rearrangements. However, in many cases the Curtius rearrangement requires excess nucleophile for the reaction to proceed to high conversions. This can complicate work procedures to deliver high-purity products. However, tandem processing and coupling of the Curtius rearrangement with an immobilized enzyme can elegantly facilitate chemoselective tagging of the residual reagent, resulting in a facile purification process under continuous flow.
Publication
A Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry
2020-01-10, Baumann, Marcus, Moody, Thomas S., Smyth, Megan, Wharry, Scott
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.
Publication
Continuous Flow Synthesis of Cyclobutenes Using LED Technology
2023-05-04, Smyth, Megan, Moody, Thomas S., Wharry, Scott, Baumann, Marcus
Cyclobutenes are highly strained ring systems of considerable synthetic interest that can be accessed via cycloaddition reactions between alkenes and alkynes. However, their traditional preparation relies on photochemical [2+2]-cycloadditions that exploit low wavelength UV radiation emitted from inefficient medium-pressure Hg-lamps. This paper reports on the development of a modern approach using a high-power LED set-up emitting at the boundary of UV-A and visible light in conjunction with a continuous flow reactor. The resulting flow process renders a series of cyclobutenes from maleimides and various commercial alkynes. This provides a more energy-efficient approach that is readily scalable to access multigram quantities of cyclobutenes in high chemical yields and short residence times. The value of these products is exemplified by flow-based hydrogenations yielding highly substituted cyclobutanes which represent sought after building blocks in modern medicinal chemistry programs.
Publication
Evaluating the Green Credentials of Flow Chemistry towards Industrial Applications
2021-08-16, Baumann, Marcus, Moody, Thomas S., Smyth, Megan, Wharry, Scott
Continuous flow chemistry is becoming an established technology platform that finds frequent application in industrial chemical manufacture with support and endorsements by the FDA for pharmaceuticals. Amongst the various advantages that are commonly cited for flow chemistry over batch processing, sustainability continues to require further advances and joint efforts by chemists and chemical engineers in both academia and industry. This short review highlights developments between 2015 and early 2021 that positively impact on the green credentials associated with flow chemistry, specifically when applied to the preparation of pharmaceuticals. An industrial perspective on current challenges is provided to whet discussion and stimulate further investment towards achieving greener modern synthetic technologies.