High-Throughput Classical Chiral Resolution Screening of Synthetic Intermediates: Effects of Resolving Agents, Crystallization Solvents, and Other Factors
Jun Qiu, Jason M. Stevens
Abstract
Using a statistical Z-score methodology, enantiomeric excess (ee) data from our historical high-throughput classical chiral resolution screens were analyzed. In total, 19 of the screens used chiral acids as resolving agents, and 20 used chiral bases. The results show clear trends in terms of the selection of chiral acids/bases in conjunction with a crystallization solvent. We rank ordered resolving agents, solvents, and resolving agent/solvent combinations by applying the Z-score method on the ee of isolated solids, and provided recommendations on executing more efficient classical chiral resolution screening for synthetic intermediates.
Topics & Concepts
EnantiomerCrystallizationResolution (logic)Chiral resolutionSolventChemistryCombinatorial chemistryEnantiomeric excessChiral derivatizing agentThroughputOrganic chemistryChiral column chromatographyEnantioselective synthesisComputer scienceCatalysisTelecommunicationsArtificial intelligenceWirelessAnalytical Chemistry and ChromatographyComputational Drug Discovery MethodsCrystallization and Solubility Studies