摘要
目的:建立茚喹诺啉[(1S/R,1’S/R)-1-(四氢吡咯-1-甲基)-2-(6-氯-2,3-二氢-茚-3-酮-1-羰基)-1,2,3,4-四氢异喹啉]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×4.6mm,5.0μm,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pH2.5)-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RR2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[（1S/R,1＇S/R）-1-（pyrrolidin-1-methyl）-2-（6-chloro-3-oxo-1,2-dihydroindene-1-carbonyl）-1,2,3,4-tetrahydroisoquinoline] 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.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2011年第5期843-846,共4页
Chinese Journal of Pharmaceutical Analysis
基金
十一五"重大新药创制"科技部重大专项(2009ZX09103-096)
