Heriot Watt University played host on Wednesday 22nd February 2023 to a fascinating seminar titled “Advances in continuous flow: from photochemistry to heterogeneous chemistry” by Dr. Manuel Nuno, the Chief Scientific Officer at Vapourtec. The seminar covered a wide range of topics in organic chemistry, from the functionalisation of C-H bonds to solid-phase approaches to peptide synthesis, and different strategies for carrying out heterogeneous reactions in continuous flow.
One of the key takeaways from the seminar was the development of photoinduced processes for functionalising C-H bonds, which have seen significant progress in recent years. The use of high power UV LED has led to a breakthrough in photocyclisation and photocatalysed C-H functionalisation reactions. The photon density that irradiates the reagents has been identified as the limiting factor in these reactions.
During his seminar at Heriot Watt University, Dr. Manuel Nuno discussed the advantages of using continuous flow for peptide synthesis. Dr. Nuno explained how the implementation of continuous flow has led to a new renaissance in peptide synthesis. By using a Variable Bed Flow Reactor (VBFR), peptides can be synthesized more efficiently, and real-time data such as UV spectra or reactor volume change can be accessed.
Working in continuous flow offers several advantages over traditional batch-wise peptide synthesis. First, it allows for a single pass of reagents through a compact resin bed which results in higher purity peptides and reduced solvent usage. Second, it provides excellent control over reaction conditions, such as mixing, temperature, pressure, and reaction time. This results in a higher yield and improved reproducibility of the reaction.
Moreover, continuous flow peptide synthesis allows for the development of anti-racemisation strategies and cleavage in flow, which can yield higher crude purity and repeatable results. Using Glucagon-like peptide-1 (GLP-1) as an example, Dr. Nuno explained how he developed anti-racemisation strategies and cleavage in flow, yielding a crude purity of over 80%.
Finally, Dr. Nuno discussed different strategies for carrying out heterogeneous reactions in continuous flow. The use of magnesium chips in a VBFR has been shown to be an effective method for generating grignard reagents, while suspended solids in flow can be handled as a slurry in tubular reactors. Dr. Nuno also highlighted the challenges associated with packing Pd on charcoal in a column without causing blockages, and highlighting the breakthrough in achieving a 6 g/h throughput of an API intermediate in a 3-phase hydrogenation reaction with the same Pd on charcoal pumped through the tubular reactor as a slurry.
Dr. Nuno’s seminar provided an intriguing glimpse into the latest advancements in organic chemistry, with the potential to significantly impact the field. His research into continuous flow for synthesising peptides and conducting heterogeneous reactions are promising areas for further exploration. The seminar’s findings are sure to spark interest in the scientific community and inspire further research and development in this field.