High-throughput purification of single compounds and libraries

J Comb Chem. 2005 Jul-Aug;7(4):546-53. doi: 10.1021/cc0498128.

Abstract

The need for increasing productivity in medicinal chemistry and associated improvements in automated synthesis technologies for compound library production during the past few years have resulted in a major challenge for compound purification technology and its organization. To meet this challenge, we have recently set up three full-service chromatography units with the aid of in-house engineers, different HPLC suppliers, and several companies specializing in custom laboratory automation technologies. Our goal was to combine high-throughput purification with the high attention to detail which would be afforded by a dedicated purification service. The resulting final purification laboratory can purify up to 1000 compounds/week in amounts ranging from 5 to 300 mg, whereas the two service intermediate purification units take 100 samples per week from 0.3 to 100 g. The technologies consist of normal-phase and reversed-phase chromatography, robotic fraction pooling and reformatting, a bottling system, an automated external solvent supply and removal system, and a customized, high-capacity freeze-dryer. All work processes are linked by an electronic sample registration and tracking system.

MeSH terms

  • Automation
  • Chemical Fractionation / instrumentation
  • Chemical Fractionation / methods*
  • Combinatorial Chemistry Techniques / instrumentation
  • Combinatorial Chemistry Techniques / methods*