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

流动化学领域将对现代合成化学产生相当大的影响，因为它是一种将自动化、增强反应性和先进合成技术融合到单一过程中的方法，极大地丰富了合成能力。流动化学的新发展将提供新的合成方法，取代现有的技术，避免了现有方法所需的加工、净化和操作，使合成时间更短，更环保。作为NSERC联盟拨款提案的一部分，我们将与Alphora Research Inc.合作开发新的流动化学方法，以解决与COVID-19相关的公司特定合成挑战。特别是，我们将重点开发合成硫氰酸胍和氯化胍的连续流化学方法，以及合成新冠病毒抗病毒药物和抗病毒前体的途径。具体而言，我们将把研究合作重点放在开发新的流动化学方法上，以应对公司特定的COVID-19相关合成挑战。本课题将重点探索和开发高纯度硫氰酸胍和氯化胍的流动合成方法。我们还将发现和开发流动合成方法，用于构建基于核糖核苷的抗病毒药物的核心结构（如remdesivir，一种已知的COVID-19抗病毒药物，在美国被批准用于紧急用途）。总体而言，我们寻求开发针对COVID-19特定合成挑战的流动化学解决方案。如下所述，流动化学原理允许开发优于当前批处理工艺的合成方法。一旦开发出合适的流动化学方法来解决上述公司特定的合成挑战，Alphora Research将尝试将这些流动化学方法转化为连续制造工艺。

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.