Strategic use of preparative chiral chromatography for the synthesis of a preclinical pharmaceutical candidate

摘要: The modern use of preparative chromatography in pharmaceutical development is illustrated by the case a recent preclinical candidate from these laboratories. synthesis employed coupling two enantiopure intermediates, each which could be resolved using chiral chromatography. SFC screening was to identify enantioselective stationary phases, and semipreparative methods derived this were used produce gram amounts intermediate for initial studies. However, larger scale resolution required translation HPLC conditions. Preparative on 30-cm i.d. column then intermediates coupled give 170 g candidate. Subsequent preparation at later-stage clinical evaluation an improved one component constructed asymmetric synthesis. Resolution other component, now more advanced intermediate, carried out newly obtained large-scale equipment. Some discussion presented varying strategies whereby can support either short-term or long-term synthetic goals development. Chirality, 2007. © 2007 Wiley-Liss, Inc.