超临界二氧化碳流体色谱拆分帕罗醇对映体的研究.pdfVIP

中国化学会第四届全国分子手性学术研讨会暨2011 绿色手性论坛 手性分子合成与拆分 超临界二氧化碳流体色谱拆分帕罗醇对映体的研究 * 鲍宗必 ，邢华斌，苏宝根，杨亦文，任其龙 (浙江大学化学工程与生物工程学系) 摘要：帕罗醇是合成手性抗抑郁药帕罗西汀的关键中间体，有效拆分帕罗醇对映体是制备帕罗 西汀工艺的重要步骤。本文研究了醇改性超临界二氧化碳流体色谱法拆分帕罗醇对映体，以多糖衍 生化手性柱Chiralpak AD-H 为固定相，重点考察了甲醇、乙醇和异丙醇等改性剂对手性识别性能的 影响，研究改性剂含量、超临界流体的压力和温度对帕罗醇对映体保留因子、对映体选择性和分离 度的影响规律。实验采用的改性剂含量范围为3~20% （体积百分比），压力范围为10~24 MPa，温 度为30~45ºC 。研究结果表明：相同改性剂含量下，甲醇为改性剂时，色谱峰形最窄，分离度最高， 甲醇为最佳改性剂；保留因子随着改性剂含量的增加而下降，对映体选择性几乎不受改性剂含量变 化的影响，但随着温度的升高而下降，低温对分离有利；压力变化对选择性的影响很小，随着压力 升高保留因子减小。 关键词：帕罗醇；手性拆分；超临界流体色谱；手性固定相 Enantioseparation of racemic paroxol on a polysaccharide-type chiral stationary phase by supercritical fluid chromatography Zongbi Bao, Huabin Xing, Baogen Su, Yiwen Yang, Qilong Ren (Zhejiang University) Abstract: Enantioseparation of paroxol, a key intermediate for synthesis of paroxetine, is of importance to preparation of paroxetine. This study demonstrated resolution of racemic paroxol on an amylose-based chiral stationary phase, i.e. Chiralpak AD-H by supercritical fluid chromatography. The effects of modifiers’ nature and content as well as pressure and temperature on the retention and selectivity were studied. The content of modifiers ranged from 3% to 20 %, and pressure varied from 10 to 24 MPa and temperature from 30 to 45ºC. This work showed that methanol is the best additive with the best resolution and narrow peak shape among the studied modifiers. It was found that retention factors decreased as increasing content of modifier while minor change in separation factor were observed. The selectivities were significantly affected by alternation of temperature. This parameter in