Microscale purification in support of high-throughput medicinal chemistry

In recent years, successful assay miniaturization has enabled the exploration of synthesis scale reduction in pharmaceutical discovery. Miniaturization of pharmaceutical synthesis and purification allows a reduction in material consumption and shortens timelines, which ultimately reduces the cost per experiment without compromising data quality. Isolating and purifying the compounds of interest is a key step in the library synthesis process. In this manuscript we describe a high-throughput purification workflow in support of microscale (1-5 mu mol or 0.5-2 mg) library synthesis. The optimized microscale purification system can routinely purify 384-well reaction plates with an analysis time of 4 min per sample. Instrument optimization, critical parameters such as column loading, delay time calibration, ultrafast pre- and post-purification analysis and library purification examples are provided.

Automated summary

The successful miniaturization of assays in recent years has enabled the exploration of reducing synthesis scale in pharmaceutical discovery, leading to lower material consumption and shorter timelines without sacrificing data quality. Isolating and purifying compounds is a key step in library synthesis, and an optimized microscale purification system can efficiently purify samples.