茚喹诺啉对映体的手性拆分及转化研究

目的: 建立茚喹诺啉 对映体的高效液相色谱拆分方法并研究它的对映体转化。 方法: 采用Chiralcel OD-RH(150 mm×4.6 mm,5.0 μm,Daicel公司)手性色谱柱在反相条件下直接拆分茚喹诺啉对映体,考察了流动相pH和比例等对茚喹诺啉对映体分离的影响。确定了较佳的拆分流动相条件为0.05 mol·L^-1磷酸二氢钾缓冲溶液(磷酸调pH 2.5)-乙腈(70∶ 30,v/v)。 结果: 发现具有两手性中心的茚喹诺啉在非不对称合成条件下仅生成SS和RR 2种光学异构体;在给质子溶剂如甲醇或水溶液中,尤其在加热或碱催化下,由于茚-3-酮-1-羰基的手性碳存在明显的消旋化,可生成4个光学异构体。 结论: 茚喹诺啉的4种光学异构体可在Chiralcel OD-RH手性色谱条件下获得良好的分离和检测,可用于其制备控制和质量检验。

Objective: To establish an HPLC method for the chiral separation and transformation study of indiquinoline enantiomers. Methods: The chiral separation of indiquinoline was achieved by using a Chiralcel OD-RH chiral (150 mm×4.6 mm,5.0 μm,Daicel) column with the mobile phase of 0.05 mol·L^-1 phosphate buffer(pH 2.5)-acetonitrile(70∶ 30,v/v).The influences of the pH,mobile phase ratios on the chiral separation have been studied. Results: The results showed that only two indiquinoline enantiomers of SS and RR were produced under non-asymmetric synthetic conditions in non-protonic solvents.But the chiral carbon in the 3-oxo-1,2-dihydroindene-1-carboxyl moiety underwent obviously racemic transformation in protonic solvents,such as methanol or aqueous solutions.The transformation can be accelerated by alkaline or elevated temperature. Conclusion: The four indiquinoline enantiomers can be separated and detected well under chiral chromatographic condition of Chiralcel OD-RH,which may be used for its preparation control and quality monitoring.