Microscale purification in support of high-throughput medicinal chemistry
2021
Barhate, Chandan L. | Donnell, Andrew F. | Davies, Merrill | Li, Ling | Zhang, Yong | Yang, Fukang | Black, Regina | Zipp, Greg | Zhang, Yingru | Cavallaro, Cullen L. | Priestley, E Scott | Weller, Harold N.
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 μmol 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.
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