The Diagnostic, PCR-based Test to Detect SARS-CoV2 RNA (COVID-19): Solving the Global Shortage of the Key Organic Building Block Using Flow Chemistry

基于 PCR 的诊断性检测 SARS-CoV2 RNA (COVID-19)：利用流动化学解决全球关键有机构件的短缺问题

• 批准号: 554166-2020
• 负责人: Organ, Michael
• 金额: $ 3.64万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=704889
• 关键词: Diagnostic; PCR; based; Test; Detect

Testing for viruses, including SARS-CoV2, the virus that caused the condition known as COVID-19, is done using a PCR-based test to detect the target viral RNA. These probes are prepared by conventional solid phase synthesis on controlled pore glass using a trifunctional linker. O-DMT-(2-N-FMOC-4'-aminobutyl)-1,3-propanediol is one of the most commonly used non-nucleoside linkers. Approximately 1 kilogram of this material has been manufactured per year for the last decade to meet all diagnostic and academic research needs; since the pandemic outbreak, the need for this material has increased more than a dozen-fold, throwing this precious material into a global backorder. Consequently, there is a concerning shortage of the test kits to diagnose patient infection for the SARS-CoV2 virus. The global supply of O-DMT-(2-N-FMOC-4'-aminobutyl)-1,3-propanediol has been provided for almost the last 20 years by Toronto Research Chemicals (TRC) in Ontario, Canada. The main step in the production of this precious material is a hydride reduction step that is very dangerous to perform, especially on a large scale. Since the need for test kits has skyrocketed, a safe and sustainable method to perform this delicate transformation has to be developed. Flow chemistry is such a method and is slowly being adopted by many small-molecule synthetic organic companies (such a pharmaceutical companies) that has been shown to be cleaner, higher yielding, and most importantly, much safer. TRC has no such expertise or facilities in house, but Prof. Michael G. Organ at the University of Ottawa is a global authority on the subject, having published and patented extensively on the subject. His group will develop a flow chemistry route for the preparation of O-DMT-(2-N-FMOC-4'-aminobutyl)-1,3-propanediol using proprietary technology invented by his team. This technology will then be transferred from his lab in Ottawa to the production facility in Toronto at TRC. This research will allow TRC to maintain it global position as the primary supplier of this important and valuable material while strengthening Canada's position as a globally recognized leader in fine chemical synthesis.

使用基于PCR的测试来检测靶病毒RNA，包括导致称为COVID-19的病毒的病毒，包括SARS-COV2，包括SARS-COV2。这些探针是通过使用三功能接头在受控孔隙玻璃上的常规固相合成来制备的。 O-DMT-（2-N-FMOC-4'-氨基丁基）-1,3-丙二醇是最常用的非核苷接头之一。在过去的十年中，每年每年制造约1公斤这种材料，以满足所有诊断和学术研究需求；自从大流行爆发以来，对这种材料的需求增加了十二倍，将这种珍贵的材料投入了全球野生储备。因此，关于SARS-COV2病毒的患者感染的测试套件短缺。 在加拿大安大略省的多伦多研究化学品（TRC）提供了几乎20年的全球O-DMT-（2-N-FMOC-4'-氨基丁基）-1,3-丙二醇的供应。生产这种珍贵材料的主要步骤是氢化物减少步骤，非常危险，尤其是在大规模上。由于需要进行测试套件的需求飞涨，因此必须开发一种安全可持续的方法来进行这种微妙的转变。流动化学是一种方法，并且正在逐渐被许多小型分子合成有机公司（此类制药公司）采用，这些公司已被证明是更清洁，产量更高，最重要的是，更安全。 TRC没有拥有这样的专业知识或设施，但是渥太华大学的Michael G. Organ教授是该主题的全球机构，已经在该主题上发表并获得了广泛的专利专利。他的小组将使用他的团队发明的专有技术来制定O-DMT-（2-N-FMOC-4'-氨基丁基）-1,3-丙二醇的流动化学途径。然后，这项技术将从他在渥太华的实验室转移到TRC多伦多的生产设施。这项研究将使TRC能够将其作为这种重要且有价值的材料的主要供应商保持全球地位，同时加强加拿大作为精细化学合成中全球认可的领导者的地位。