Bradow James, Riley Frank, Philippe Laurence, Yan Qi, Schuff Brandon, Harris Guy H
Pfizer Research & Development, Groton, CT, USA.
Dynamic Extractions, Inc., Monmouth Junction, NJ, USA.
J Sep Sci. 2015 Dec;38(23):3983-91. doi: 10.1002/jssc.201500574. Epub 2015 Dec 2.
A fully automated countercurrent chromatography system has been constructed to rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent system series and translate the results to preparative scale separations. The system utilizes "on-demand" preparation of the heptane/ethyl acetate/methanol/water solvent system upper and lower phases. Elution-extrusion countercurrent chromatography was combined with non-dynamic equilibrium injection reducing the screening time for each heptane/ethyl acetate/methanol/water system to 17 min. The result enabled solvent system development to be reduced to under 2 h. The countercurrent chromatography system was interfaced with a mass spectrometer to allow selective detection of target components in crude medicinal chemistry reaction mixtures. Mass-directed preparative countercurrent chromatography purification was demonstrated for the first time using a synthetic tetrazole epoxide derived from a routine medicinal chemistry support workflow.
已构建了一个全自动逆流色谱系统，用于快速筛选常用的庚烷/乙酸乙酯/甲醇/水溶剂体系系列，并将结果转化为制备规模的分离。该系统利用“按需”制备庚烷/乙酸乙酯/甲醇/水溶剂体系的上相和下相。洗脱-挤压逆流色谱与非动态平衡进样相结合，将每个庚烷/乙酸乙酯/甲醇/水体系的筛选时间缩短至17分钟。这一结果使溶剂体系开发时间缩短至2小时以内。该逆流色谱系统与质谱仪相连，以便选择性检测粗制药物化学反应混合物中的目标成分。首次使用源自常规药物化学支持工作流程的合成四唑环氧化物，展示了质量导向的制备型逆流色谱纯化。
