The use of enabling technologies and continuous methods to enhance chemical synthesis is a vibrant area of research, gaining increasing attention from laboratories in academia and industry. Yet many prominent synthesis procedures have not changed for decades and require significant manual intervention from bench chemists, which may lead to the waste of both human and material resources. The research described herein details how chemistry has been bridged with engineering to address this issue in a world increasingly focussed on sustainability and efficiency. This thesis is divided into four chapters. The first describes the development of a novel Internet-based process control system which is applied to automate a cycling catalytic process. The capability of the system to conduct multi-dimensional self-optimisation processes is shown, where it is integrated with an on-line mass spectrometer and inline infrared spectrometer to drive optimisation against customisable multicomponent evaluation functions. Chapter 2 details the successful synthesis of the anti-cancer drug candidate AZ82. The control system is applied to assist with a number of these steps, including facilitating the integration between batch and flow processes on a single reactor platform. A new distillation unit to assist with downstream solvent switching is also described. In Chapter 3, the cloud-based nature of the control system is exploited by moving it to servers residing in Tokyo. The ability of the system to accelerate the drug development process is highlighted with the autonomous self-optimisation and synthesis of four active pharmaceutical ingredient targets: tramadol, lidocaine, bupropion and isoniazid. In the case of bupropion, the system maintained steady-state operation of a telescoped two-step process for an extended period. A researcher in Los Angeles was able to initiate and monitor all processes, via Japan, in real-time as they occurred in our laboratory in Cambridge, UK. Finally, Chapter 4 describes the development of a new parallel column supercritical fluid chromatography (SFC) unit that is capable of separating a multicomponent product stream continuously exiting a flow reactor. The versatility of the SFC unit is showcased with the telescoped synthesis of isoniazid in which all stages, including the SFC process itself, are managed by the control system without researcher intervention.
Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:723543 |
Date | January 2017 |
Creators | Fitzpatrick, Daniel Ewert |
Contributors | Ley, Steven Victor |
Publisher | University of Cambridge |
Source Sets | Ethos UK |
Detected Language | English |
Type | Electronic Thesis or Dissertation |
Source | https://www.repository.cam.ac.uk/handle/1810/267427 |
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