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

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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.