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.

对病毒的检测，包括导致新冠肺炎的SARS-CoV2病毒，是使用基于聚合酶链式反应的测试来检测目标病毒rna的。这些探针是使用三官能团连接剂在受控多孔玻璃上通过传统的固相合成制备的。O-DMT-(2-N-FMOC-4‘-aminobutyl)-1，3-propanediol是最常用的非核苷连接物之一。在过去十年中，每年大约生产1公斤这种材料，以满足所有诊断和学术研究需求；自大流行爆发以来，对这种材料的需求增加了十几倍，使这种宝贵的材料成为全球缺货。因此，诊断患者感染SARS-CoV2病毒的检测试剂盒存在令人担忧的短缺。 近20年来，O-DMT-(2-N-FMOC-4‘-aminobutyl)-1，3-propanediol的全球供应一直由加拿大安大略省的多伦多研究化学品公司提供。生产这种贵重材料的主要步骤是氢化物还原步骤，这一步骤执行起来非常危险，特别是在大规模的情况下。由于对测试套件的需求激增，必须开发一种安全和可持续的方法来执行这种微妙的转变。流动化学就是这样一种方法，并逐渐被许多小分子合成有机公司(如制药公司)所采用，这些公司已被证明更清洁、更高产量，最重要的是，更安全。TRC内部没有这样的专业知识或设施，但渥太华大学的Michael G.Organ教授是这一主题的全球权威，他在这一主题上发表了大量的著作并获得了专利。他的团队将利用他的团队发明的专利技术，开发一条制备O-DMT-(2-N-FMOC-4‘-aminobutyl)-1，3-propanediol的流动化学路线。然后，这项技术将从他在渥太华的实验室转移到位于多伦多的TRC生产设施。这项研究将使TRC保持其作为这种重要和有价值材料的主要供应国的全球地位，同时加强加拿大作为全球公认的精细化学合成领先者的地位。