手性萃取剂与液-液萃取拆分对映体技术研究进展

doi:10.16085/j.issn.1000-6613.2015.12.032

摘要/Abstract

摘要： 手性对映体的拆分是当前备受关注的一个研究领域。手性对映体的拆分方法有多种, 手性液-液萃取拆分法是其中有较好发展前景的一种手性对映体拆分技术。本文概述了手性液-液萃取技术的基本原理, 并进一步对酒石酸类手性萃取剂、环糊精类手性萃取剂、冠醚类手性萃取剂、金属络合物类手性萃取剂等不同种类手性萃取剂及其研究进展进行了综述。分析表明, 手性液-液萃取拆分技术对外消旋体特别是药物外消旋体的拆分有较好的效果, 随着对手性萃取剂研究的进一步深入, 手性液-液萃取有望成为一种手性化合物拆分的重要方式。

关键词: 手性萃取剂, 萃取分离, 手性拆分, 药物

Abstract: Techniques for separating enantiomers are the focus of concern currently. Among numerous techniques for separating enantiomers,such as crystallization,chromatography,enantioselective liquid-liquid extraction is one of the most promising techniques for industrial application. This review firstly introduced the basic principles of the enantioselective liquid-liquid extraction technique,and then summarized various chiral extractants including tartrates-based extractants,cyclodextrin-based extractants,crown ether based-extractants,metal complexes-based extractants,and other enantioselective extraction agents as well as their recent advances. Researches indicate that enantioselective liquid-liquid extraction shows remarkable enantioseparation ability for enantiomers especially racemic pharmaceuticals. With the developing of new chiral extractants,enantioselective liquid-liquid extraction can be an important technique for enantiomers separation.

Key words: chiral extractants, extraction separation, enantioseparation, pharmaceuticals

中图分类号:

TQ460.6

黄钰清, 鲍宗必, 邢华斌, 杨亦文, 张治国, 任其龙. 手性萃取剂与液-液萃取拆分对映体技术研究进展[J]. 化工进展, 2015, 34(12): 4324-4332.

HUANG Yuqing, BAO Zongbi, XING Huabin, YANG Yiwen, ZHANG Zhiguo, REN Qilong. Chiral extractants and enantioselective liquid-liquid extraction[J]. Chemical Industry and Engineering Progree, 2015, 34(12): 4324-4332.

参考文献

[1] Lorenz H,Seidel-Morgenstern A. Processes to separate enantiomers[J]. Angewandte Chemie International Edition,2014,53(5):1218-1250.
[2] 王彦广,吕萍,张殊佳,等. 有机化学[M]. 北京:化学工业出版社,2008:59-60.
[3] 黄蓓,杨立荣,吴坚平. 手性拆分技术的工业应用[J]. 化工进展,2002,21(6):375-380.
[4] Xu D,Li Z,Ma S. Novozym-435-catalyzed enzymatic separation of racemic propargylic alcohols. A facile route to optically active terminal aryl propargylic alcohols[J]. Tetrahedron Letters,2003,44(33):6343-6346.
[5] Lorenz H,Perlberg A,Sapoundjiev D,et al. Crystallization of enantiomers[J]. Chemical Engineering and Processing:Process Intensification,2006,45(10):863-873.
[6] Feitsma K G,Drenth B F H. Chromatographic separation of enantiomers[J]. Pharmaceutisch Weekblad,1988,10(1):1-11.
[7] Schuur B,Verkuijl B J V,Minnaard A J,et al. Chiral separation by enantioselective liquid-liquid extraction[J]. Organic & Biomolecular Chemistry,2011,9(1):36-51.
[8] 李俊,蔡水洪. 手性化合物的萃取拆分研究[J]. 化学世界,2001,42(5):233-236.
[9] Bowman N S,McCloud G T,Schweitzer G K. Partial resolutionn of some organic racemates by solvent extraction[J]. Journal of the American Chemical Society,1968,90(14):3848-3852.
[10] 岑仲浙,蔡水洪. 手性溶剂萃取麻黄碱差向异构体[J]. 化工学报,2000,51(3):418-420.
[11] 易健民,陈立根,唐课文,等. 手性溶剂萃取分离顺式二氯菊酸对映体[J]. 化学通报,2008,71(9):701-705.
[12] Ren Z,Zeng Y,Hua Y,et al. Enantioselective liquid-liquid extraction of racemic ibuprofen by l-tartaric acid derivatives[J]. Journal of Chemical & Engineering Data,2014,59(8):2517-2522.
[13] 唐课文,周春山. L-酒石酸酯立体选择性萃取分离扁桃酸对映体[J]. 应用化学,2003,20(11):1108-1110.
[14] 周丹,刘佳佳,唐课文. 手性酯类萃取剂萃取拆分a-环己基扁桃酸外消旋体[J]. 分析测试学报,2006,25(6):49-52.
[15] 黄可龙,胡卫国,焦飞鹏,等. 组合手性萃取拆分克伦特罗外消旋体[J]. 分析科学学报,2007,23(3):283-286.
[16] Tan B,Luo G S,Qi X,et al. Enantioselective extraction of d,l-tryptophan by a new chiral selector:Complex formation with di(2-ethylhexyl) phosphoric acid and O,O'-dibenzoyl-(2R,3R)-tartaric acid[J]. Separation and Purification Technology,2006,49(2):186-191.
[17] Tan B,Luo G,Wang J. Enantioseparation of amino acids by co-extractants with di (2-ethylhexyl) phosphoric acid and tartaric acid derivatives[J]. Tetrahedron:Asymmetry,2006,17(6):883-891.
[18] Jiao F,Yang W,Huang D,et al. Enantioseparation of ofloxacin enantiomers by mixed extractants in biphasic system[J]. Separation Science and Technology,2012,47(13):1971-1976.
[19] Sunsandee N,Pancharoen U,Rashatasakhon P,et al. Enantioselective separation of racemic amlodipine by two-phase chiral extraction containing O,O'-Dibenzoyl-(2S,3S)-tartaric acid as chiral selector[J]. Separation Science and Technology,2013,48(15):2363-2371.
[20] Tan B,Luo G,Wang J. Extractive separation of amino acid enantiomers with co-extractants of tartaric acid derivative and Aliquat-336[J]. Separation and Purification Technology,2007,53(3):330-336.
[21] 松丽涛. 对映体手性萃取分离及包结作用研究[D]. 长沙:中南大学,2010.
[22] 苗家兵. 包合反应手性萃取分离芳香酸对映体及其动力学研究[D]. 长沙:中南大学,2010
[23] Zhou C S,Xu P,Tang K W,et al. Enantioselective extraction of clorprenaline enantiomers with hydrophilic selector of sulfobutylether-β-cyclodextrin by experiment and modeling[J]. Journal of Central South University,2014,21:891-899.
[24] 唐课文,陈圆圆,刘佳佳. 双相 (O/W) 识别手性萃取分离萘普生对映体[J]. 中国药学杂志,2008,43(8):620-623.
[25] 陈圆圆. 双相(O/W)识别手性萃取分离对映体的研究[D]. 长沙:中南大学,2008
[26] Szwed K,Górecki M,Frelek J,et al. Enantioselective extraction system containing binary chiral selectors and chromatographic enantioseparation method for determination of the absolute configuration of enantiomers of cyclopentolate[J]. Chromatographia,2013,76(23-24):1603-1611.
[27] Tang K,Yi J,Huang K,et al. Biphasic recognition chiral extraction:A novel method for separation of mandelic acid enantiomers[J]. Chirality,2009,21(3):390-395.
[28] 高明章,杨奕群,许遵乐. 手性冠醚的研究进展[J]. 有机化学,2001,21(7):477-484.
[29] Colera M,Costero A M,Gaviña P,et al. Synthesis of chiral 18-crown-6 ethers containing lipophilic chains and their enantiomeric recognition of chiral ammonium picrates[J]. Tetrahedron:Asymmetry,2005,16(15):2673-2679.
[30] Bredikhina Z A,Eliseenkova R M,Fayzullin R R,et al. Synthesis and extraction properties of some lariat ethers derived from the spontaneously resolved guaifenesin,3-(2-methoxyphenoxy) propane-1,2-diol[J]. Arkivoc,2011,10:16-32.
[31] Steensma M,Kuipers N J M,De Haan A B,et al. Identification of enantioselective extractants for chiral separation of amines and aminoalcohols[J]. Chirality,2006,18(5):314-328.
[32] Demirel N,Bulut Y,Hoşgören H. Enantioselective transport and liquid-liquid extraction of amino acids as their potassium and sodium salts by optically active diaza-18-crown-6 ethers[J]. Chirality,2004,16(6):347-350.
[33] 唐课文,陈国斌,易健民,等. 基于手性配体交换反应立体选择性萃取分离氧氟沙星对映体[J]. 化学学报,2004,62(17):1621-1625.
[34] Verkuijl B J V,Minnaard A J,de Vries J G,et al. Chiral separation of underivatized amino acids by reactive extraction with palladium-BINAP complexes[J]. The Journal of Organic Chemistry,2009,74(17):6526-6533.
[35] Verkuijl B J V,Schuur B,Minnaard A J,et al. Chiral separation of substituted phenylalanine analogues using chiral palladium phosphine complexes with enantioselective liquid-liquid extraction[J]. Organic & Biomolecular Chemistry,2010,8(13):3045-3054.
[36] Tang K W,Fu T,Zhang P L. Enantioselective liquid-liquid extraction of (D,L)-valine using metal-BINAP complex as chiral extractant[J]. Journal of Chemical Technology and Biotechnology,2013,88(10):1920-1929.
[37] Zhang P L,Liu C,Tang K W,et al. Studies on enantioselective liquid-liquid extraction of amino-(4-nitro-phenyl)-acetic acid enantiomers:Modeling and optimization[J]. Chirality,2014,26(2):79-87.
[38] Zhang P L,Luo J J,Tang K W,et al. Kinetics of enantioselective liquid-liquid extraction of phenylglycine enantiomers using a BINAP-copper complex as chiral selector[J]. Chemical Papers,2014,68(10):1317-1324.
[39] Zhang P,Liu C,Tang K,et al. Modeling and optimizing the biphasic enantioselective partitioning of 2-fluoro-phenylalanine enantiomers with binap-metal complexes as chiral selector[J]. Journal of Solution Chemistry,2015,44(1):112-130.
[40] Verkuijl B J V,Schoonen A K,Minnaard A J,et al. The use of N-type ligands in the enantioselective liquid-liquid extraction of underivatized amino acids[J]. European Journal of Organic Chemistry,2010,2010(27):5197-5202.
[41] Tsukube H,Shinoda S,Uenishi J,et al. Molecular recognition with lanthanide (Ⅲ) tris (β-diketonate) complexes:Extraction,transport,and chiral recognition of unprotected amino acids[J]. Inorganic Chemistry,1998,37(7):1585-1591.
[42] Reeve T B,Cros J P,Gennari C,et al. A practical approach to the resolution of racemic N-benzyl-a-amino acids by liquid-liquid extraction with a lipophilic chiral salen-cobalt (III) complex[J]. Angewandte Chemie International Edition,2006,45(15):2449-2453.
[43] Schuur B,Floure J,Hallett A J,et al. Continuous chiral separation of amino acid derivatives by enantioselective liquid-liquid extraction in centrifugal contactor separators[J]. Organic Process Research & Development,2008,12(5):950-955.
[44] Schuur B,Winkelman J G M,de Vries J G,et al. Experimental and modeling studies on the enantio-separation of 3,5-dinitrobenzoyl-(R),(S)-leucine by continuous liquid-liquid extraction in a cascade of centrifugal contactor separators[J]. Chemical Engineering Science,2010,65(16):4682-4690.
[45] Huang H,Nandhakumar R,Choi M,et al. Enantioselective liquid-liquid extractions of underivatized general amino acids with a chiral ketone extractant[J]. Journal of the American Chemical Society,2013,135(7):2653-2658.
[46] Verkuijl B J V,de Vries J G,Feringa B L. 3,3'-diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines[J]. Chirality,2011,23(1):34-43.
[47] Lacour J,Goujon G C,Torche H S,et al. Efficient enantioselective extraction of tris (diimine) ruthenium (II) complexes by chiral,lipophilic TRISPHAT anions[J]. Angewandte Chemie International Edition,2000,39(20):3695-3697.
[48] Baragaña B,Blackburn A G,Breccia P,et al. Enantioselective transport by a steroidal guanidinium receptor[J]. Chemistry:A European Journal,2002,8(13):2931-2936.
[49] Peng Y,He Q,Zuo B,et al. Enantioselective liquid-liquid extraction of zopiclone with mandelic acid ester derivatives[J]. Chirality,2013,25(12):952-956.
[50] Schuur B,Blahušiak M,Vitasari C R,et al. Selector screening for enantioseparation of DL-α-methyl phenylglycine amide by liquid-liquid extraction[J]. Chirality,2015,27(2):123-130.