The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. 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, will be available in the quantities required. We used retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In several instances, the software utilizes C–H functionalization logic, and one route to umifenovir employs functionalization of six C–H bonds. The general strategy we apply can be used to identify distinct starting materials, and relieve stress on existing supply chains.

Miniaturization is a tactic employed in many technologies to accelerate discovery and enable new applications such as systems-level evaluation. The miniaturization of chemical synthesis to the limits of chemoanalytical and bioanalytical limits of detection could accelerate drug discovery by increasing the amount of experimental data collected per milligram of material consumed. Here we demonstrate the miniaturization of popular reactions used in drug discovery such as reductive amination, N-alkylation, N-Boc deprotection and Suzuki coupling for utilization in 1.2 μL reaction droplets. Reaction methods were evolved to perform in high boiling solvents at room temperature, enabling the diversification of precious starting materials, such as the complex natural product staurosporine.

<p>High throughput experimentation (HTE) is an increasingly important tool in the study of chemical synthesis. While the hardware for running HTE in the synthesis lab has evolved significantly in recent years, there remains a need for software solutions to navigate data rich experiments. We have developed the software, phactor™, to facilitate the performance and analysis of HTE in a chemical laboratory. phactor™ allows experimentalists to rapidly design arrays of chemical reactions in 24, 96, 384, or 1,536 wellplates. Users can access online reagent data, such as a lab inventory, to populate wells with experiments and produce instructions to perform the screen manually, or with the assistance of a liquid handling robot. After completion of the screen, analytical results can be uploaded for facile evaluation, and to guide the next series of experiments. All chemical data, metadata, and results are stored in a machine-readable format.</p>