FlowCoV: Development of Flow Chemistry Methods Related to COVID-19

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The field of flow chemistry is poised to have a considerable impact on modern synthetic chemistry as it is an approach that incorporates automation, enhanced reactivity and advanced synthesis techniques into a single process that greatly enriches synthetic capabilities. New developments using flow chemistry will provide for new synthetic methods that will replace existing techniques and avoid the need for the work-up, purification and manipulation required by current methods, making syntheses shorter and greener. As part of this NSERC Alliance grant proposal, we will partner with Alphora Research Inc. to develop new flow chemistry methods that seek to solve several company-specific synthetic challenges related to COVID-19. In particular, we will focus on the development of continuous flow chemistry methods for the synthesis of guanidinium thiocyanate and guanidinium chloride, as well as routes to the synthesis of proposed COVID-19 antivirals and antiviral precursors. Specifically, we will focus our research collaboration on the development of new flow chemistry methods that will meet company-specific COVID-19 related synthetic challenges. For this research proposal, we will focus on the discovery and development of flow synthesis methods for the high-purity flow synthesis of guanidinium thiocyanate and guanidinium chloride. We will also discover and develop of flow synthesis methods for the construction of the core structure of ribonucleoside-based antivirals (such as remdesivir, a known COVID-19 antiviral that is approved in the United States for emergency use). Overall, we seek to develop flow chemistry solutions to COVID-19 specific synthetic challenges. As outlined below, flow chemistry principles allow for the development of synthetic methods that are superior to current batch processes. It is the expectation that once suitable flow chemistry methods have been developed to address the company-specific synthetic challenges outlined above, Alphora Research will attempt the translation of these flow chemistry methods to continuous manufacturing processes.