【摘要】：脂肪族手性胺類化合物是醫(yī)藥原藥和中間體的常見化合物結(jié)構(gòu),其一般無紫外吸收或紫外吸收很弱,建立并確定脂肪族手性胺e.e.值測定方法具有重要的意義。本文采用使無紫外吸收的脂肪族胺衍生化為芳香胺進(jìn)行液相分析。方法一采用普通衍生化試劑對樣品進(jìn)行衍生化,增強(qiáng)紫外吸收,然后采用手性色譜柱進(jìn)行檢測。以3-氨基哌啶與仲丁胺為例進(jìn)行探索。首先3-氨基哌啶以苯甲酰氯為衍生化試劑,產(chǎn)物在波長254 nm、柱溫30℃、流速0.8 mL/min采用HPLC-UV方法CHIRAL-AGP檢測e.e.值。3-氨基哌啶與苯甲酰氯的單取代產(chǎn)物,檢測流動相為2:98(V:V)的異丙醇:15 mmol/L KH2PO4(pH=6.5),(S)和(R)-衍生物的保留時間7.15min、9.910min。3-氨基哌啶與苯甲酰氯的雙取代產(chǎn)物,檢測流動相為8%乙腈+92%15 mmol/L KH2PO4(pH=6.5),(R)和(S)-衍生物的保留時間23.047 min、37.967min。其次仲丁胺與苯甲酰氯衍生化反應(yīng)產(chǎn)物進(jìn)行HPLC-UV分析,其液相條件:色譜柱為CHIRAL-AGP;流動相為2%異丙醇+98%15 mmol/L磷酸二氫鉀(用磷酸氫二鉀調(diào)pH=6.0);檢測波長254 nm;流速0.8 mL/min;柱溫30℃。(S)和(R)-衍生物保留時間2.793 min、5.445 min。方法二采用手性衍生化試劑對樣品進(jìn)行衍生化,由對映異構(gòu)體變成非對映異構(gòu)體,然后采用普通色譜柱進(jìn)行檢測。以3-氨基丁醇和2-氨基丁醇為例進(jìn)行研究。3-氨基丁醇和2-氨基丁醇衍生物,在波長254 nm、檢測溫度30℃、流速1.0 mL采用HPLC-UV法迪馬C18色譜柱測定e.e.值。首先3-氨基丁醇的檢測,其與(R)-1-甲基-2-萘乙酰氯反應(yīng)產(chǎn)物,檢測流動相為40%乙腈-60%NaH2PO4(c=0.1%,pH4.5),(R)和(S)-衍生物的保留時間5.747 min、7.662 min。3-氨基丁醇與(R)-1-苯基乙磺酰氯反應(yīng)產(chǎn)物,檢測流動相為乙腈-水(體積比80:20),(R)和(S)-衍生物的保留時間2.652 min、3.172min。其次2-氨基丁醇的檢測,其與(R)-1-甲基-2-萘乙酰氯反應(yīng)產(chǎn)物,檢測流動相為80%甲醇-20%鹽酸溶液(c=0.2 mol/L),(S)和(R)-衍生物的保留時間6.123 min、4.143min。2-氨基丁醇與(R)-1-苯基乙磺酰氯反應(yīng)產(chǎn)物,檢測流動相70%甲醇-30%50mmol/L醋酸鈉水溶液,(R)和(S)-衍生物的保留時間6.538 min、11.356 min。通過HPLC-UV測定纈氨酸e.e.值。液相條件為:色譜柱為SUMICHIRAL OA-6100手性柱;流動相為2 mmol/L CuSO4;檢測波長為220 nm;流速為0.8 mL/min;柱溫為30℃。D與L-纈氨酸保留時間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，

本文編號：2265558