High-Throughput Classical Chiral Resolution Screening of Synthetic Intermediates: Effects of Resolving Agents, Crystallization Solvents, and Other Factors

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.

采用统计学的Z分数方法，对历史高通量经典手性分辨筛选中的对映过量（ee）数据进行了分析。总计19个筛选过程中使用了手性酸作为分辨剂，而20个筛选过程中则使用了手性碱。结果表明，在手性酸/碱与结晶溶剂的选择上呈现了明显的趋势。通过将Z分数方法应用于分离固体样品的ee，我们对分辨剂、溶剂以及分辨剂/溶剂组合进行了排序，并针对合成中间体的经典手性分辨筛选提出了优化建议。