Advances in industrial organic synthesis are essential for the successful commercialization of innovative and efficient processes. From the production of ammonia by artificial nitrogen fixation through to modern manufacturing workflows for peptide therapeutics, these important developments in process chemistry would be impossible without cutting-edge technologies and collaboration across disciplines.
The Journal of Organic Chemistry published a Special Issue, put together by guest editors Spencer Dreher at Merck and John Ragan at Pfizer, celebrating advances in industrial organic synthesis that are currently shaping process chemistry’s future. Featuring papers from more than 40 different organizations across 14 countries, this Special Issue highlights the research that is driving more effective and efficient outcomes in process chemistry and includes perspectives on tomorrow’s workflows from leaders at some of the world’s most influential research-based organizations.
Below, we look at some of the topics featured in this Special Issue and the impact these advances in chemical technology are expected to have on industrial organic synthesis in the years to come.
Industrial Organic Synthesis: Celebrating Progress
As highlighted by the issue’s guest editors in their Editorial, “Excellence in Industrial Organic Synthesis 2019: The Past, Present, and Future,” industrial chemists have made a profound impact on the modern world. The list of scientists who have been awarded the Nobel Prize in Chemistry in recognition of industrial research is as long as it is diverse. Alfred Nobel was himself a highly successful industrial chemist.
Industrial organic synthesis has long played a key role in addressing society’s healthcare challenges, and the advances made along the way have shaped other industries too. Take the discovery and development of antibiotics such as the glycopeptide vancomycin, for example. The advances in chemistry that led to its production not only had an immediate clinical benefit but accelerated research in other fields, including biosynthesis, total synthesis, and analytical chemistry. Similarly, the advanced industrial processes used to develop anti-HIV protease inhibitors have had a lasting impact beyond medicine and helped to usher in today’s ‘quality by design’ paradigm of process development.
Process optimization remains front and center in industrial-scale pharmaceutical synthesis, and as part of this Special Issue, Shawn Walker and colleagues at Amgen Inc. have highlighted aspects of their work in the development of robust chemical processes for molecules on a multi-kilogram scale. Their Perspective, “Molecular Complexity as a Driver for Chemical Process Innovation in the Pharmaceutical Industry,” features a focus on fragment design, asymmetric synthesis, and novel synthetic reagents. These and other advances in process chemistry continue to accelerate the delivery of innovative and much-needed medicines to patients.
Putting Green Chemistry at the Heart of Industrial Organic Synthesis
Currently, one of the biggest drivers of change in industrial organic synthesis is the growing recognition that more must be done to minimize process chemistry’s environmental impact. As part of this Special Issue, Kai Rossen, editor-in-chief of the ACS journal Organic Process Research & Development, provided an invited Perspective, “Greening Organic Chemistry with Process Chemistry,” that discusses the importance of assessing the holistic green credentials of a process, rather than just individual steps or reagents. Here, the sharing of guidance and experience between the industrial and academic communities could play a key part in developing this mindset.
Green chemistry considerations are influencing process optimization across a wide range of industries, not least the pharmaceutical sector. In 2016, the ACS Green Chemistry Institute Pharmaceutical Roundtable identified the urgent need for greener processes for the synthesis of therapeutic peptides. In a Perspective, “Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production,” the Roundtable team summarized the current challenges in this area and highlighted possible solutions. Again, encouraging collaboration and communication between academia, pharmaceutical companies, and contract research and manufacturing organizations will be an essential part of shaping tomorrow’s processes.
Applying Novel Technologies to Advance Today’s Industrial Processes
Evolving pressures such as the increasing safety and efficacy requirements for new medicines, more challenging biological targets, greater commercial competition, and the ongoing drive to make R&D more efficient continue to push industrial chemists to find new ways of working. This Special Issue highlights a wealth of innovative synthesis tools and technologies that are already helping chemists achieve better outcomes using fewer resources.
New technologies for the miniaturization of chemical processes and experimentation using parallel synthesis techniques are bringing forth opportunities for process chemistry on a scale previously inaccessible to most laboratories and production lines. The use of high-throughput experimentation to guide process optimization, as well as novel applications of flow chemistry and in-line monitoring, highlight the growing importance of these tools for industrial organic synthesis.
At the same time, ongoing advances in informatics are generating more valuable information more quickly to support the preparation, evaluation, and design of new molecules. Here, big data’s application to industrial processes is enabling chemists to use real-world information to optimize syntheses, and advances in machine learning and artificial intelligence are helping chemists process complex information more quickly to make more informed decisions. This Special Issue highlights the use of advanced computational algorithms to accelerate drug development, an application that’s relevant to the pharmaceutical industry and beyond.
Stay Up to Date with the Latest Advances in Your Interest Areas
The remarkable advances in industrial organic synthesis highlighted in this Special Issue reflect the diversity of technologies that are influencing this space. The latest developments in disciplines at the edge or just beyond the field of organic chemistry are continually pushing the limits of the possible and supporting the creation of industrial processes that are faster, more efficient, and have a lower environmental impact.
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