新型氨基酸衍生物手性固定相的制备及应用

doi:10.11944/j.issn.1000-0518.2018.01.170030

摘要/Abstract

摘要：

氨基酸是手性小分子,其选择和固定化的方法,有助于开发新的“刷型”手性固定相(CSP)。分别以L-缬氨酸和L-丙氨酸为原料制备了10种新型氨基酸衍生物手性固定相(CSPs),包括8种氨基酸三嗪衍生物CSPs(CSP-1~CSP-8)和两种对甲基苯甲酰氨基酸CSPs(CSP-9~CSP-10),在正相色谱条件下,考察了所合成的CSPs对邻、间和对硝基苯酚位置异构体以及萘普生乙酯、丙环唑、苯醚甲环唑、戊唑醇、己唑醇和联萘酚6种外消旋样品的分离能力。结果表明,硝基苯酚的3种位置异构体在CSP-1~CSP-3和CSP-6~CSP-8上获得较好分离。相同条件下,由丙氨酸制得的CSPs对外消旋样品表现出更好的手性识别能力,萘普生乙酯在CSP-6上获得基线分离。由化学软件Gaussian 09计算出的L-丙氨酸三取代三嗪衍生物CSP-Ⅵ与萘普生乙酯的两个光学异构体之间相互作用的结合能分别为52.51和133.9 kJ/mol,也说明了手性选择子与R、S形成的非对映配合物的稳定性不同,Gaussian 09所给出的结合构型图显示手性选择子与样品之间有明显的氢键作用。 Gaussian 09的计算结果有助于认识CSPs的手性识别机理。

关键词: 氨基酸衍生物, 手性固定相, 手性拆分, Gaussian 09

Abstract:

Ten novel amino acid derived chiral stationary phases(CSPs), including eight amino acid modified triazine derived CSPs(CSP-1~CSP-8) and two N-p-methylbenzoyl L-amino acid CSPs(CSP-9~CSP-10), were prepared from L-valine and L-alanine. The chiral recognition ability of these CSPs was evaluated for regioisomers of o-, m-, p-nitrophenol and six racemates of naproxen ethyl ester, propiconazole, difenoconazole, tebuconazole, hexaconazole, 1,1'-bi-2-naphthol, under normal phase mode. The results show that CSP-1~CSP-3 and CSP-6~CSP-8 exhibit good selectivity for three regioisomers of nitrophenol. The CSPs obtained from L-alanine show better enantioselective recognition toward the racemates, which leads to a baseline separation of naproxen ethyl ester on CSP-6. Meanwhile, the binding mode and association energy of L-alanine three-substituted triazine derivative CSP Ⅵ with R or S naproxen ethyl ester were investigated by computational simulation with Gaussian 09 software, and hydrogen bonding was found to be a significant factor on the enantioselective recognition.

Key words: amino acid derivatives, chiral stationary phases, chiral separation, Gaussian 09

韩小茜, 蔺云云, 李臻, 刘文华, 石宁宁, 王农. 新型氨基酸衍生物手性固定相的制备及应用[J]. 应用化学, 2018, 35(1): 68-74.

HAN Xiaoqian, LIN Yunyun, LI Zhen, LIU Wenhua, SHI Ningning, WANG Nong. Preparation and Application of Novel Bonded L-Valine and L-Alanine Derived Chiral Stationary Phases[J]. Chinese Journal of Applied Chemistry, 2018, 35(1): 68-74.

参考文献

[1]	Silvia R,Anna R,Joseph J P,et al.Enantiomers Separation by Nano-liquid Chromatography:Use of a Novel Sub-2 μm Vancomycin Silica Hydride Stationary Phase[J]. J Chromatogr A,2015,1381:149-159.
[2]	Elodie L,Claude V,Saïd Y,et al.Design of Experiments for Enantiomeric Separation in Supercriticalfluid Chromatography[J]. J Pharm Biomed Anal,2016,120:297-305.
[3]	Patel D C,Wahab M F,Armstrong D W,et al.Advances in High-throughput and High-efficiency Chiral Liquid Chromatographic Separations[J]. J Chromatogr A,2016,1467:2-18.
[4]	CAO Zhigang,LI Laisheng,CHENG Biaoping,et al.Separation and Determination of Diniconazole Enantiomers in Pear on β-Cyclodextrin-based Stationary Phase by HPLC[J]. J Instrum Anal,2016,35(1):16-22(in Chinese). 曹志刚,李来生,程彪平,等. β-环糊精液相色谱固定相拆分和测定梨中烯唑醇对映体含量[J]. 分析测试学报,2016,35(1):16-22.
[5]	Scriba G K E. Chiral Recognition in Separation Science[J]. J Chromatogr A,2016,1467:56-78.
[6]	BIN Qin,FU Keqin,ZHANG Junjun,et al.Preparation and Application of Novel Brush-type Chiral Stationary Phases Based on Phenylglycine Derivatives[J]. Chinese J Synth Chem,2015,23(1):1-6(in Chinese). 宾琴,付克勤,张俊俊,等. 新型苯甘氨酸衍生物“刷型”手性固定相的制备及其应用[J]. 合成化学,2015,23(1):1-6.
[7]	HE Xinrui,WU Zhongyong,YE Yongli,et al.Research Progress on Detection of Amino Acids by High Performance Liquid Chromatography[J]. J Instrum Anal,2016,35(7):922-928(in Chinese). 赫欣睿,武中庸,叶永丽,等. 高效液相色谱法测定氨基酸的研究进展[J]. 分析测试学报,2016,35(7):922-928.
[8]	CHANG Yinxia,ZHOU Lingling,XIANG Lan,et al.Separation of Various Racemates Using D-Phenylglycine as Chiral Stationary Phase[J]. J Instrum Anal,2007,26(1):107-109(in Chinese). 常银霞,周玲玲,向兰,等. D-苯甘氨酸手性固定相的制备及对多种手性化合物的拆分[J]. 分析测试学报,2007,26(1):107-109.
[9]	SHEN Conghua,LI Ping,TANG Tao,et al.Preparation of a New Stationary Phase with s-Triazine and Amide Embedded and Its Application in Separation of Basic Compounds[J]. Chinese J Chromatogr,2013,31(11):1035-1039(in Chinese). 沈从华,李萍,唐涛,等. 一种内嵌三嗪环酰胺极性基团新型固定相的制备及其在碱性化合物分离中的应用[J]. 色谱,2013,31(11):1035-1039.
[10]	WANG Quan,WANG Kun,SUN Lehua. Synthesis of 2,4,6-Tris(amino acids)-1,3,5-triazine[J]. Chem Reag,2012,34(12):1148-1150(in Chinese). 汪权,王坤,孙乐花. 2,4,6-三氨基酸取代-1,3,5-均三嗪衍生物的合成研究[J]. 化学试剂,2012,34(12):1148-1150.
[11]	Chen Z L,Fuyumuro T,Watabe K,et al.Influence of Spacers and Organic Modifiers on Chromatographic Behaviors on Chiral Diamide Stationary Phase with N-(3,5-Dimethylbenzoyl)-d-phenylglycine[J]. Anal Chim Acta,2004,518:181-189.
[12]	NONG Ruiyu,KONG Jiao,ZHANG Junhui,et al.Chiral Metal-organic Framework {[Co(L-trp)(bpe)(H2O)]·H2O·NO3}n Used for High Performance Liquid Chromatographic Separation[J]. Chem J Chinese Univ,2016,37(1):19-25(in Chinese). 农蕊瑜,孔娇,章俊辉,等. 手性金属-有机骨架材料{[Co(L-trp)( bpe)(H2O)]·H2O·NO3}n用于高效液相色谱的拆分性能[J]. 高等学校化学学报,2016,37(1):19-25.
[13]	WEI Enqi,LI Lirong,WU Yufeng,et al.Progress on Analysis Methods for Nitroaromatic Pollutants in Water Matrix[J]. J Instrum Anal,2016,35(8):1071-1078(in Chinese). 魏恩棋,李利荣,吴宇峰,等. 水体中硝基芳烃类有机污染物分析方法研究进展[J]. 分析测试学报,2016,35(8):1071-1078.
[14]	LIU Yu,ZHANG Tonglai,YANG Li,et al.Simultaneous Determination of 14 Nitrophenol Compounds by QuEChERS-Ultra Performance Liquid Chromatography[J]. Chinese J Energ Mater,2015,23(1):73-79(in Chinese). 刘玉,张同来,杨利,等. QuEChERS-超高效液相色谱法同时测定硝基酚类物质方法的研究[J]. 含能材料,2015,23(1):73-79.
[15]	GOU Gaozhang,WANG Zefeng,HUANG Zhaolong,et al.Application of Gaussian 09 Software in Electronic Circular Dichroism Spectroscopy Teaching[J]. Chinese J Chem Edu,2016,37(2):61-64(in Chinese). 苟高章,王泽锋,黄兆龙,等. Gaussian 09软件在电子圆二色谱教学中的应用[J]. 化学教育,2016,37(2):61-64.