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SYNTHIA COVID Cernak Lab Paper 08-05-20.pdf (4.91 MB)
Reinforcing the Supply Chain of COVID-19 Therapeutics with Expert-Coded Retrosynthetic Software
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submitted on 05.08.2020 and posted on 07.08.2020by Yingfu Lin, Zirong Zhang, Babak Mahjour, Di Wang, Rui Zhang, Eunjae Shim, Andrew McGrath, Yuning Shen, Nadia Brugger, Rachel Turnbull, Shashi Jasty, Sarah Trice, Tim Cernak
Supply chains become stressed when demand for essential products increases rapidly in times of crisis. This year, the
scourge of coronavirus highlighted the fragility of diverse supply chains, affecting the world’s pipeline of hand sanitizer,
toilet paper,2 and pharmaceutical starting materials.
3 Many drug repurposing studies are now underway.
4 If a winning
therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed
to synthesize it,5 will be available in the quantities required to satisfy global demand. We show the use of a retrosynthetic
artificial intelligence (AI)
6-10 to navigate multiple parallel synthetic sequences, and arrive at plausible alternate reagent
supply chains for twelve investigational COVID-19 therapeutics. In many instances, the AI utilizes C–H functionalization
11-13 and we have experimentally validated several syntheses, including a route to the antiviral umifenovir that
requires functionalization of six C–H bonds. This general solution to chemical supply chain reinforcement will be useful
during global disruptions, such as during a pandemic.