脂肪族手性胺e.e.值测定方法研究

发布时间：2018-10-12 09:06

【摘要】：脂肪族手性胺类化合物是医药原药和中间体的常见化合物结构,其一般无紫外吸收或紫外吸收很弱,建立并确定脂肪族手性胺e.e.值测定方法具有重要的意义。本文采用使无紫外吸收的脂肪族胺衍生化为芳香胺进行液相分析。方法一采用普通衍生化试剂对样品进行衍生化,增强紫外吸收,然后采用手性色谱柱进行检测。以3-氨基哌啶与仲丁胺为例进行探索。首先3-氨基哌啶以苯甲酰氯为衍生化试剂,产物在波长254 nm、柱温30℃、流速0.8 mL/min采用HPLC-UV方法CHIRAL-AGP检测e.e.值。3-氨基哌啶与苯甲酰氯的单取代产物,检测流动相为2:98(V:V)的异丙醇:15 mmol/L KH2PO4(pH=6.5),(S)和(R)-衍生物的保留时间7.15min、9.910min。3-氨基哌啶与苯甲酰氯的双取代产物,检测流动相为8%乙腈+92%15 mmol/L KH2PO4(pH=6.5),(R)和(S)-衍生物的保留时间23.047 min、37.967min。其次仲丁胺与苯甲酰氯衍生化反应产物进行HPLC-UV分析,其液相条件:色谱柱为CHIRAL-AGP;流动相为2%异丙醇+98%15 mmol/L磷酸二氢钾(用磷酸氢二钾调pH=6.0);检测波长254 nm;流速0.8 mL/min;柱温30℃。(S)和(R)-衍生物保留时间2.793 min、5.445 min。方法二采用手性衍生化试剂对样品进行衍生化,由对映异构体变成非对映异构体,然后采用普通色谱柱进行检测。以3-氨基丁醇和2-氨基丁醇为例进行研究。3-氨基丁醇和2-氨基丁醇衍生物,在波长254 nm、检测温度30℃、流速1.0 mL采用HPLC-UV法迪马C18色谱柱测定e.e.值。首先3-氨基丁醇的检测,其与(R)-1-甲基-2-萘乙酰氯反应产物,检测流动相为40%乙腈-60%NaH2PO4(c=0.1%,pH4.5),(R)和(S)-衍生物的保留时间5.747 min、7.662 min。3-氨基丁醇与(R)-1-苯基乙磺酰氯反应产物,检测流动相为乙腈-水(体积比80:20),(R)和(S)-衍生物的保留时间2.652 min、3.172min。其次2-氨基丁醇的检测,其与(R)-1-甲基-2-萘乙酰氯反应产物,检测流动相为80%甲醇-20%盐酸溶液(c=0.2 mol/L),(S)和(R)-衍生物的保留时间6.123 min、4.143min。2-氨基丁醇与(R)-1-苯基乙磺酰氯反应产物,检测流动相70%甲醇-30%50mmol/L醋酸钠水溶液,(R)和(S)-衍生物的保留时间6.538 min、11.356 min。通过HPLC-UV测定缬氨酸e.e.值。液相条件为:色谱柱为SUMICHIRAL OA-6100手性柱;流动相为2 mmol/L CuSO4;检测波长为220 nm;流速为0.8 mL/min;柱温为30℃。D与L-缬氨酸保留时间4.415 min、13.770 min。
[Abstract]:Aliphatic chiral amines are the common structures of pharmaceutical raw drugs and intermediates, which generally have no or weak UV absorption, so the aliphatic chiral amines are established and determined. The method of value determination is of great significance. In this paper, aliphatic amines without UV absorption were derivatized to aromatic amines for liquid phase analysis. Methods: the samples were derivatized by ordinary derivatization reagent to enhance UV absorption and then detected by chiral chromatographic column. Taking 3-aminoperidol and sec-butylamine as examples to explore. Firstly, 3-aminoperidol was used as derivatization reagent with benzoyl chloride as derivatization reagent. The product was determined by CHIRAL-AGP at a wavelength of 254 nm, at 30 鈩，

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