水溶性β-环糊精包合反应萃取药物对映体的研究
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摘要
手性和手性技术是当今化学研究的前沿和热点之一。单一对映体的制备是制药和精细化学品工业急待解决的重大基础问题之一。手性溶剂萃取具有适用范围广、可连续操作、易于工业化生产、生产成本相对较低等优点,成为最具发展潜力和应用前景的一种单一对映体制备技术。手性溶剂萃取技术的发展很大程度上依赖于萃取剂的改进。水溶性β-环糊精衍生物因良好的手性选择性和亲水性,用于疏水性药物对映体的分离有着独特的优势,是一种极具潜力的手性萃取剂。
本文采用水溶性β-环糊精衍生物作为萃取剂,研究了某些疏水性药物对映体的手性溶剂萃取分离。通过实验考查了萃取条件对萃取性能的影响。进行了萃取机理的研究,建立反应萃取模型。通过模型预测和实验结果的比较,对模型进行修正。运用分配系数、分离因子、对映体过量和萃取性能因子等参数表征萃取性能,综合模型预测和实验结果对萃取体系进行优化。
第二章是理论研究部分,本文针对水溶性环糊精衍生物强亲水性及疏水性药物对映体能在两相间分配的特点,采用了水相均相反应机理。综合对映体的物理分配、离解平衡及对映体与萃取剂的包合反应平衡等,建立了反应萃取模型用于萃取体系的模拟。与已报道的模型建立过程不同,本文结合药理研究论文中关于离子态药物对映体也在两相间分配的报道,在建立的模型中引入了离子分配系数。
第三章到第六章是对四种药物对映体的手性萃取研究。实验研究了有机溶剂、环糊精衍生物类型、水相pH值、萃取剂浓度、温度等因素对萃取性能的影响,并测定了模型的相关参数。在实验研究基础上,得到了每个对映体最合适的萃取体系。结合相关参数,将模型应用于每个对映体的最合适体系,通过实验结果和模型预测的比较,对模型进行修正。在修正后的模型基础上,构建多元函数模型。经多元函数模型的模拟和优化获取最佳操作条件和参数。结果表明水溶性β-环糊精衍生物对所研究的药物对映体都有一定的识别能力,对同一药物对映体,结构不同的萃取剂优先识别的对映异构体是一致的,但识别能力各不相同。有机溶剂、水相pH值、温度、萃取剂浓度等对萃取性能有显著的影响,但对不同的分离对象影响规律有差别。本文建立的反应萃取模型需要针对具体的药物对映体进行修正,修正后的模型对所研究的四个体系的模拟都很成功,表明本文的理论研究具有普遍的适用性。离子分配的引入使模型预测的准确性大大提高。四种药物对映体都得到了各自的最佳萃取操作条件和参数。以上研究结果表明本文建立的模型是模拟药物对映体手性溶剂萃取体系的有力工具,并能为工程计算和设计提供参考。
Chirality and chiral technology play an important role in the field of chemical research, nowadays. The availability of enantiopure compounds is of primary importance in the pharmaceutical and fine chemical industry. Chiral solvent extraction is considered as a very promising technology for the production of enantiopure compounds because it possesses a wide range of applications, can be operated continuously and economically and can be scaled up to an industrial scale easily. The development of chiral solvent extraction requires efficient chiral extractants. Hydrophilicβ-cyclodextrin (β-CD) are a kind of very promising chiral extractant for the separation of hydrophobic drug enantiomers because of their good chiral recognition ability and hydrophility.
This thesis deals with the enantioselective extraction of some hydrophobic drug enantiomers to an aqueous phase of hydrophilicβ-CD solution. The influence of process variables on extraction efficiency was investigated experimentally. The extraction mechanism was investigated and a reactive extraction model was established. The model was validated by comparison of the model predictions with the experimental results. Extraction performances were evaluated using distribution ratio, enantioselectivity, enantiomeric excess and performance factor and the extraction systems were optimized by modeling and experiment.
In Chapter 2, the theory of chiral solvent extraction was studied. Consideringβ-CD derivatives are highly hydrophilic and the hydrophobic drug enantiomers can distribute over the organic and aqueous phases, homogeneous aqueous phase reaction mechanism is applied. An inclusion reactive extraction model was established involving equilibrium of physical distribution, dissociation and inclusion complexation between enantiomers andβ-CD extractant. Some pharmacological studies have reported the distribution of ionic species between organic and aqueous phases, the model in this thesis therefore contains the physical distribution coefficient of ionic enantiomers, which is different from the models that have been reported.
In Chapters 3-6, chiral solvent extraction of four drug enantiomers was investigated. The effects of process variables such as types of organic solvents andβ-CD derivatives, concentration of selector, pH and temperature, on extraction efficiency were investigated and important parameters of the model were determined experimentally. The most suitable extraction system for each drug enantiomers was obtained by experiment. Reactive extraction model was applied for each drug enantiomers. The models were then validated by comparison of the model predictions with the experimental results. Multivariate function models were then established based on the validated models. Modeling and optimization based on the multivariate function models were carried out to obtained the optimal extraction conditions and coefficients. Results show thatβ-CD derivatives can recognize all the drug enantiomers studied. For typical drug enantiomers,β-CD derivatives with different chemical structures preferentially recognize the same enantiomer but with different recognition abilities. Organic solvents type, concentration of extractant, pH and temperature strongly influence the extraction efficiency, but the pattern of their influence is different on different enantiomers. Application of the reactive extraction model need to be adjusted to each specific system and all the four systems are modeled successfully after the adjustment, which indicate the theory investigation of this thesis can be generally applied. Addition of the ionic physical distribution greatly improve the accuracy of the model predictions. The optimum conditions and coefficients of the four enantiomers were srparately obtained. The presented data indicates that the model is a powerful tool for modeling chiral solvent extraction system and can provide information for the engineering calculation and design.
本文采用水溶性β-环糊精衍生物作为萃取剂,研究了某些疏水性药物对映体的手性溶剂萃取分离。通过实验考查了萃取条件对萃取性能的影响。进行了萃取机理的研究,建立反应萃取模型。通过模型预测和实验结果的比较,对模型进行修正。运用分配系数、分离因子、对映体过量和萃取性能因子等参数表征萃取性能,综合模型预测和实验结果对萃取体系进行优化。
第二章是理论研究部分,本文针对水溶性环糊精衍生物强亲水性及疏水性药物对映体能在两相间分配的特点,采用了水相均相反应机理。综合对映体的物理分配、离解平衡及对映体与萃取剂的包合反应平衡等,建立了反应萃取模型用于萃取体系的模拟。与已报道的模型建立过程不同,本文结合药理研究论文中关于离子态药物对映体也在两相间分配的报道,在建立的模型中引入了离子分配系数。
第三章到第六章是对四种药物对映体的手性萃取研究。实验研究了有机溶剂、环糊精衍生物类型、水相pH值、萃取剂浓度、温度等因素对萃取性能的影响,并测定了模型的相关参数。在实验研究基础上,得到了每个对映体最合适的萃取体系。结合相关参数,将模型应用于每个对映体的最合适体系,通过实验结果和模型预测的比较,对模型进行修正。在修正后的模型基础上,构建多元函数模型。经多元函数模型的模拟和优化获取最佳操作条件和参数。结果表明水溶性β-环糊精衍生物对所研究的药物对映体都有一定的识别能力,对同一药物对映体,结构不同的萃取剂优先识别的对映异构体是一致的,但识别能力各不相同。有机溶剂、水相pH值、温度、萃取剂浓度等对萃取性能有显著的影响,但对不同的分离对象影响规律有差别。本文建立的反应萃取模型需要针对具体的药物对映体进行修正,修正后的模型对所研究的四个体系的模拟都很成功,表明本文的理论研究具有普遍的适用性。离子分配的引入使模型预测的准确性大大提高。四种药物对映体都得到了各自的最佳萃取操作条件和参数。以上研究结果表明本文建立的模型是模拟药物对映体手性溶剂萃取体系的有力工具,并能为工程计算和设计提供参考。
Chirality and chiral technology play an important role in the field of chemical research, nowadays. The availability of enantiopure compounds is of primary importance in the pharmaceutical and fine chemical industry. Chiral solvent extraction is considered as a very promising technology for the production of enantiopure compounds because it possesses a wide range of applications, can be operated continuously and economically and can be scaled up to an industrial scale easily. The development of chiral solvent extraction requires efficient chiral extractants. Hydrophilicβ-cyclodextrin (β-CD) are a kind of very promising chiral extractant for the separation of hydrophobic drug enantiomers because of their good chiral recognition ability and hydrophility.
This thesis deals with the enantioselective extraction of some hydrophobic drug enantiomers to an aqueous phase of hydrophilicβ-CD solution. The influence of process variables on extraction efficiency was investigated experimentally. The extraction mechanism was investigated and a reactive extraction model was established. The model was validated by comparison of the model predictions with the experimental results. Extraction performances were evaluated using distribution ratio, enantioselectivity, enantiomeric excess and performance factor and the extraction systems were optimized by modeling and experiment.
In Chapter 2, the theory of chiral solvent extraction was studied. Consideringβ-CD derivatives are highly hydrophilic and the hydrophobic drug enantiomers can distribute over the organic and aqueous phases, homogeneous aqueous phase reaction mechanism is applied. An inclusion reactive extraction model was established involving equilibrium of physical distribution, dissociation and inclusion complexation between enantiomers andβ-CD extractant. Some pharmacological studies have reported the distribution of ionic species between organic and aqueous phases, the model in this thesis therefore contains the physical distribution coefficient of ionic enantiomers, which is different from the models that have been reported.
In Chapters 3-6, chiral solvent extraction of four drug enantiomers was investigated. The effects of process variables such as types of organic solvents andβ-CD derivatives, concentration of selector, pH and temperature, on extraction efficiency were investigated and important parameters of the model were determined experimentally. The most suitable extraction system for each drug enantiomers was obtained by experiment. Reactive extraction model was applied for each drug enantiomers. The models were then validated by comparison of the model predictions with the experimental results. Multivariate function models were then established based on the validated models. Modeling and optimization based on the multivariate function models were carried out to obtained the optimal extraction conditions and coefficients. Results show thatβ-CD derivatives can recognize all the drug enantiomers studied. For typical drug enantiomers,β-CD derivatives with different chemical structures preferentially recognize the same enantiomer but with different recognition abilities. Organic solvents type, concentration of extractant, pH and temperature strongly influence the extraction efficiency, but the pattern of their influence is different on different enantiomers. Application of the reactive extraction model need to be adjusted to each specific system and all the four systems are modeled successfully after the adjustment, which indicate the theory investigation of this thesis can be generally applied. Addition of the ionic physical distribution greatly improve the accuracy of the model predictions. The optimum conditions and coefficients of the four enantiomers were srparately obtained. The presented data indicates that the model is a powerful tool for modeling chiral solvent extraction system and can provide information for the engineering calculation and design.
引文
[1]Eliel E L, Wilen S H, Doyle M P. Basic organic stereochemistry. New York:John Wiley & Sons, Inc.,2001.608～611
[2]Steensma M. Chiral separation of amino-alcohols and amines by fractional reactive extraction:[Thesis]. Enschede, Netherlands:University of Twente,2005
[3]Hutt A J. Drug chirality:impact on pharmaceutical regulation. Chirality,1991,3: 161～164.
[4]郭莉娜,侯仲轲,陈灿等.不对称催化反应合成手性药物的研究进展.精细化工中间体,2006,36(2)：1～4.
[5]尤启冬,林国强.手性药物.北京：化学工业出版社,2004.3～5
[6]French A N. Clean, green chiral reactions-Just Add a Salt. Science,2010, 328(5984):1365～1366.
[7]Dondoni A, Massi A. Asymmetric Organocatalysis:From Infancy to Adolescence. Angewandte Chemie International Edition,2008,47(25):4638～4660
[8]MacMillan D W C. Commentary The advent and development of organocatalysis. Nature,2008455,304～308
[9]Knowles W S. L-Dopa process and intermediates. US Patent,4005127, 1977-01-25
[10]Glueck D S. Catalytic Asymmetric Synthesis of Chiral Phosphanes. Chemistry A European Journal,2008,14(24):7108～7117
[11]Zuend S J, Coughlin M P, Lalonde M P, et al. Scaleable catalytic asymmetric Strecker syntheses of unnatural a-amino acids. Nature,2009,461:968～970
[12]Kwiatkowski P, Beeson T D, Conrad J C, et al. Enantioselective Organocatalytic a-Fluorination of Cyclic Ketones. Journal of the American Chemical Society,2011, 133(6):1738～1741
[13]Cannon J S, Kirsch S F, Overman L E. Catalytic Asymmetric Synthesis of Chiral Allylic Esters. Journal of the American Chemical Society,2010,132 (43):15185～ 15191
[14]Gridnev I D, Watanabe M, Wang H, et al. Mechanism of Enantioselective C-C Bond Formation with Bifunctional Chiral Ru Catalysts:NMR and DFT Study. Journal of the American Chemical Society,2010,132(46):16637～16650
[15]Maier N M, Franco P, Lindner W. Separation of enantiomers:needs, challenges, perspectives. Journal of Chromatography:A,2001,906(1-2):3～33
[16]Srinivas N R, Barbhaiya R H, Midha K K. Enantiomeric drug development: Issues, considerations, and regulatory requirements. Journal of Pharmaceutical Sciences,2001,90(9):1205～1215
[17]Ward T J, Baker B A. Chiral Separations. Analytical Chemistry,2008,80 (12): 4363～4372
[18]D'Oria E, Karamertzanis P G, Price S L. Spontaneous Resolution of Enantiomers by Crystallization:Insights from Computed Crystal Energy Landscapes. Crystal Growth & Design,10(4):1749～1756
[19]Wood W M L. Crystal science techniques in the manufacture of chiral compounds. In:Collins A N, Sheldrake G N, Crosby J, eds. Chirality in Industry II. John Wiley &Sons Inc.,1997.119～115
[20]Bhushan R, Tanwar S. Direct TLC resolution of atenolol and propranolol into their enantiomers using three different chiral selectors as impregnating reagents. Biomedical Chromatography,2008,22(9):1028～1034
[21]朱全红,马果东,邓芹英.薄层色谱用苯基异氰酸酯衍生化的伊环糊精键合固定相的制备及应用.分析化学,2000,28(3)：349～352
[22]Bhushan R, Parshad Vineeta. Resolution of (±)-ibuprofen using L-arginine-impregnated thin-layer chromatography. Journal of Chromatography:A,1996,721(2): 369～372
[23]Bertrand M, Chabin A, Brack A, et al. Separation of amino acid enantiomers VIA chiral derivatization and non-chiral gas chromatography. Journal of Chromatography: A,2008,1180(1-2):131～137
[24]Shamoto T, Tasaki Y, Okada T. Chiral ice chromatography. Journal of the American Chemical Society,2010,132(38):13135～13137
[25]Bhushan R, Kumar V. Indirect resolution of baclofen enantiomers from pharmaceutical dosage form by reversed-phase liquid chromatography after derivatization with Marfey's reagent and its structural variants. Biomedical Chromatography,2008,22(8):906～911
[26]Karthikeyan K, Arularasu G. T, Ramadhas R, et al. Development and validation of indirect RP-HPLC method for enantiomeric purity determination of D-cycloserine drug substance. Journal of Pharmaceutical and Biomedical Analysis,2011,54(4): 850～854
[27]Ilisz I, Berkecz R, Peter A. Application of chiral derivatizing agents in the high-performance liquid chromatographic separation of amino acid enantiomers:A review. Journal of Pharmaceutical and Biomedical Analysis,2008,47(1):1～15
[28]Ameyibor E, Stewart J T. Enantiomeric HPLC Separation of Selected Chiral Drugs Using Native and Derivatized β-Cyclodextrins as Chiral Mobile Phase Additives. Journal of Liquid Chromatography & Related Technologies,1997,20(6): 855～869
[29]Surapaneni S, Khalil S KW. Resolution of terfenadine enantiomers by reversed phase-high performance liquid chromatography using β-cyclodextrin as mobile phase additive. Journal of Pharmaceutical and Biomedical Analysis,1996,14:1631～1634
[30]Van Overbeke A, Baeyens W, Oda H, et al. Direct Enantiomeric HPLC Separation of Several 2-Arylpropionic Acids, Barbituric Acids and Benzodiazepines on Chiralcel OJ-R Chiral Stationary Phase. Chromatographia,1996,43(11-12):599～ 606
[31]Hoffmann C V, Pell R, Lmmerhofer M, et al. Synergistic Effects on Enantioselectivity of Zwitterionic Chiral Stationary Phases for Separations of Chiral Acids, Bases, and Amino Acids by HPLC. Analytical Chemistry,2008,80 (22): 8780～8789
[32]Rubioa N, Minguillon C. Preparative enantioseparation of (±)-N-(3,4-cis-3-decyl-1,2,3,4-tetrahydrophenanthren-4-yl)-3,5-dinitrobenzamide by centrifugal partition chromatography. Journal of Chromatography:A,2010,1217(8):1183～1190
[33]Gomes P S, Zabkova M, Zabka M, et al. Separation of chiral mixtures in real SMB units:The Flex SMB-LSRE. AIChE Journal,2010,56(1):125～142
[34]Petersson P, Markides K E. Chiral separation performed by supercritical fluid chromatography. Journal of Chromatography:A,1994,666(1-2):381～394
[35]Taylor L T. Supercritical Fluid Chromatography. Analytical Chemistry,2010,82 (12):4925～4935
[36]Mangelings D, Heyden Y V. Chiral separations in sub-and supercritical fluid chromatography. Journal of Separation Science,2008,31(8):1252～1273
[37]Shamsi S A, Danielson N D. Utility of ionic liquids in analytical separations. Journal of Separation Science,2007,30(11):1729～1750
[38]Stalcup A M. Chiral separations by capillary electrophoresis. Journal of the American Chemical Society,2010,132(24):8525～8526.
[39]Kostal V, Katzenmeyer J, Arriaga E A. Capillary Electrophoresis in Bioanalysis. Analytical Chemistry,2008,80 (12):4533～4550
[40]Juvancz Z, Kendrovics R B, Ivanyi R, et al. The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis,2008,29(8):1701～1712
[41]Zhang Z, Wu R, Wu M, et al. Recent progress of chiral monolithic stationary phases in CEC and capillary LC. Electrophoresis,2010,31(9):1457～1466
[42]Martinez-Giron A B, Crego A L, Gonzalez M J, et al. Enantiomeric separation of chiral polycyclic musks by capillary electrophoresis:Application to the analysis of cosmetic samples. Journal of Chromatography:A,2010,1217(7):1157～1165
[43]Lau S Y, Uzir M H, Kamaruddin A H, et al. Lipase-catalyzed dynamic kinetic resolution of racemic ibuprofen ester via hollow fiber membrane reactor:Modeling and simulation. Journal of Membrane Science,2010,357(1-2):109～121.
[44]Lau S Y, Gonawan F N, Subhash B, et al. Conceptual design and simulation of a plant for the production of high purity (S)-ibuprofen acid using innovative enzymatic membrane technology. Chemical Engineering Journal,2011,166(2):726-737
[45]Miyako E, Maruyama T, Kamiya F, et al. Highly enantioselective separation using a supported liquid membrane encapsulating surfactant-enzyme complex. Journal of the American Chemical Society,2004,126(28):8622～8623
[46]Krieg H M, Lotter J, Keizer K, et al. Enrichment of chlorthalidone enantiomers by an aqueous bulk liquid membrane containing β-cyclodextrin. Journal of Membrane Science,2000,167(1):33～45
[47]Rmaile H H, Schlenoff J B. Optically active polyeletrolyte multilayers as membranes for chiral separations. Journal of the American Chemical Society,2003, 125(22):6602-6603
[48]Yoshikawa M, Murakoshi K, Kogita T, et al. Chiral separation membranes from modified polysulfone having myrtenal-derived terpenoid side groups. European Polymer Journal,2006,42(10):2532-2539
[49]唐课文,周春山,蒋新宇.支载液膜双有机相萃取分离氧氟沙星外消旋体.中国科学(B),2002,32(6)：491-496
[50]姚传义,张金红,俞耀庭.酶法手性化合物的合成与拆分.化工进展,2000,19(6)：35-50
[51]Bhushan I, Parshad R, Qazi G N, et al. Lipase enzyme immobilization on synthetic beaded macroporous copolymers for kinetic resolution of chiral drugs intermediates. Process Biochemistry,2008,43(4):321-330
[52]Abergel R J, Zawadzka A M, Hoette T M, et al. Enzymatic Hydrolysis of Trilactone Siderophores:Where Chiral Recognition Occurs in Enterobactin and Bacillibactin Iron Transport(1). Journal of the American Chemical Society,2009,131 (35):12682～12692
[53]Van Tol J, Bert A, Duine J, et al. Description of hydrolase enantioselectivity must be based on the actual kinetic resolution of glycidyl(2,3-epoxy-l-propyl) butyrate by pig pancreas lipase. Biocatalysis and Biotransformation,1995,12(2):99-117
[54]Pellissier H. Recent developments in dynamic kinetic resolution. Tetrahedron, 2008,64(8):1563～1601
[55]Schuur B, Verkuijl B J V, Minnaard A J, et al. Chiral separation by enantioselective liquid-liquid extraction. Organic & Biomolecular Chemistry,2011,9: 36～51
[56]Steensma M, Kuipers N J M, de Haan A B, et al. Modelling and experimental evaluation of reaction kinetics in reactive extraction for chiral separation of amines, amino acids and aminoalcohols. Chemical Engineering Science,2007,62(5):1395～ 1407
[57]Bowman N S, McCloud G T, Schweitzer G K. Partial resolution of some organic racemates by solvent extraction. Journal of the American Chemical Society,1968, 90(14):3848～3852
[58]Schweitz, G K, Supernaw I R, Bowman N S J. The solvent extraction resolution of some optically-active neutral chelates. Journal of Inorganic and Nuclear Chemistry, 1968,30(7):1885～1887
[59]Molnar P, Thorey P, Bansaghi G, et al. Resolution of racemic trans-1,2-cyclohexanediol with tartaric acid. Tetrahedron:Asymmetry,2008, (19): 1587～1592
[60]Tan B, Luo G S, Wang J D. Extraction separation of amino acid enantiomers with co-extractions of tartaric acid derivative and Aliquat-336. Separation and Purification Technology,2007,53(3):330～336
[61]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.应用化学,2003,11(20)：1108～1110
[62]唐课文,周春山.疏水性L酒石酸酯立体选择性萃取分离氯噻酮对映体.分析化学,2004,32(1)：63～66
[63]唐课文,周春山.疏水性相转移手性溶剂萃取分离叔丁喘宁对映体.分析化学,2004,3(32)：278～282
[64]唐课文,陈国斌,周春山.手性配体立体选择性萃取分离扁桃酸对映体.无机化学学报,2004,3：339～344
[65]唐课文,周春山,蒋新宇.支载液膜双有机相萃取分离氧氟沙星外消旋体[J]. 中国科学(B),2002,32(6)：491～496
[66]Nazarenko A Y, Huszthy P, Bradshaw J S, et al. Journal of Inclusion Phenomena and Macrocyclic Chemistry,1995,20(1) 13～22
[67]Newcomb M, Toner J L, Helgeson R C, et al. Host-guest complexation.20. Chiral recognition in transport as a molecular basis for a catalytic resolving machine. Journal of the American Chemical Society,1979,101(17):4941～4947
[68]Peacock S C, Domeier L A, Gaeta F C A, et al. Host-guest complexation.13. High chiral recognition of amino esters by dilocular hosts containing extended steric barriers. Journal of the American Chemical Society,1978,100(26):8190～8202
[69]Takeuchi T, Horikawa R, Tanimura T. Enantioselective solvent extraction of neutral DL-amino acids in two-phase systems containing N-n-alkyl-L-proline derivatives and copper(Ⅱ) ion. Analytical Chemistry,1984,56 (7):1152～1155
[70]Koska J, Haynes C A. Modelling multiple chemical equilbria in chiral partition systems. Chemical Engineering Science,2001,56:5853～5864
[71]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. Journal of Organic Chemistry,2009,74(17):6526～6533
[72]Hallett A J, Kwant G J, de Vries J G. Continuous Separation of Racemic 3,5-Dinitrobenzoyl-Amino Acids in a Centrifugal Contact Separator with the Aid of Cinchona-Based Chiral Host Compounds. Chemistry A European Journal,2009,15: 2111～2120
[73]Kellner K H, Blasch A, Chmiel H, et al. Enantioseparation of N-Protected Alpha-Amino Acid Derivatives by Liquid-Liquid Extraction Technique Employing Stereoselective Ion-Pair Formation With a Carbamoylated Quinine Derivative. Chirality,1997,9(3):268～273
[74]Maier N M, Schefzick S, Lombardo G M, et al. Elucidation of the Chiral Recognition Mechanism of Cinchona Alkaloid Carbamate-Type Receptors for 3,5-Dinitrobenzoyl Amino Acids. Journal of the American Chemical Society,2002, 124(29):8611～8629
[75]Schuur B, Winkelmam J G M, Heeres H J. Equilibrium studies on enantioselective liquid-liquid amino acid extraction using a cinchona alkaloid extractant. Industrial & Engineering Chemistry Research,2008,47:10027～10033
[76]陈慧,王孙琴.环糊精类高效液相色谱固定相的研究进展.色谱,1999,17(6)：533～538
[77]刘育,尤长城,张衡益.超分子化学：合成受体的分子识别与组装.天津：南开大学出版社.2001,166～169
[78]Armstrong D W, Ward T J, Armstrong R J, et al. Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes. Science, 1986,232(4754):1132～1135
[79]Escandadr G M. Spectroscopic study of sadlicylate-cyclodextrin systems in the presence and absence of alcohols. Spectrochimica Acta, Part A:Molecular Spectroscopy,1999,55(9):1743～1752
[80]Szeman J, Ganzler K, Salgo A, et al. Effect of the degree of substitution of cyclodextrin derivatives on chiral separations by high-performance liquid chromatography and capillary electrophoresis. Journal of Chromatography: A,1996, 728(1-2):423～431
[81]Koppenhoefer B, Eppedein U, Christian B, et al. Separation of enatiomers of drugs by capillary electrophoresis Ⅲ.β-cyclodextrin as chiral solvating agent. Journal of Chromatography:A,1996,735(1-2):333～343
[82]Liu Y, Song Y, Wang H, et al. Selective Binding of Steroids by 2,2'-Biquinoline-4,4'-dicarboxamide-Bridged Bis((3-cyclodextrin):Fluore-scence Enhancement by Guest Inclusion. Journal of Organic Chemistry,2003,68(9):3687～3690
[83]Liu Y, Li X Q, Chen Y, et al. Spectrophotometric Study of Selective Binding Behaviors of Dye Molecules by Pyridineand Bipyridine-Modified β-Cyclodextrin Derivatives with a Functional Tether in Aqueous Solution. Journal of Physical Chemistry B,2004,108(50):19541～19549
[84]Venema F, Nelissen H F M, Berthault P, et al. Synthesis, Conformation, and Binding Properties of Cyclodextrin Homo- and Heterodimers Connected through Their Secondary Sides. Chemistry A European Journal,1998,4(11):2237～2250
[85]Jiao F P, Chen X Q, Hu W G, et al. Enantioselective extraction of mandelic acid enantiomers by L-dipentyl tartrate and beta-cyclodextrin as binary chiral selectors. Chemical Papers,2007,61(4):326～328
[86]Tang K, Chen Y, Huang K, et al. Enantioselective Resolution of chiral aromatic acids by biphasic recognition chiral extraction. Tetrahedron:Asymmetry,2007,18: 2399～2408
[87]Nishizawa H, Tahara K, Hayashida A, et al. Continuous Separation Method with Liquid Particle Extractor:Enantioseparation of (±)-Mandelic Acid. Analytical Sciences,1993,9(5):611～615
[88]Tang K, Miao J, Liu Y, et al. Equilibrium Studies on Reactive Extraction of α-Cyclohexyl-mandelic Enantiomers Using Hydrophilic β-Cyclodextrin Derivatives Extractants. Chinese Journal of Chemistry 2010,28(8):1444～1450
[89]Tang K, Miao J, Zhou T, et al. Reaction kinetics in reactive extraction for chiral separation of a-cyclohexyl-mandelic acid enantiomers with hydroxypropyl-β-cyclodextrin. Chemical Engineering Science,2011,66(3):397～404
[90]Tang K, Miao J, Zhou T, et al. Equilibrium studies on reactive extraction of naproxen enantiomers using hydrophilic β-cyclodetrin derivatives extractants. Journal of Inclusion Phenomena and Macrocyclic Chemistry,2010,69(1-2):213～220
[91]Erdal K, Aysegul K, Abdulkadir S. Synthesis of new chiral calix[4]arene diamide derivatives for liquid phase extraction of a-amino acid methylesters. Tetrahedron: Asymmetry,2006,17(10):1514～1520
[92]Davis A P, Lawless L J. Steroidal guanidinium receptors for the enantioselective recognition of N-acyl-α-amino acids. Chemical Communications.1999, (1),9～10.
[93]Davis, J. T. G-Quartets 40 Years Later:From 5'-GMP to Molecular Biology and Supramolecular Chemistry. Angewandte Chemie, International Edition,2004,43(6): 668～698
[94]Tang K, Yi J, Liu Y, et al. Enantioselective separation of R,S-phenylsuccinic acid by biphasic recognition chiral extraction. Chemical Engineering Science,2009,64: 4081～4088
[95]Keurentjes J T F, Nabuurs L W M, Vegter E A. Liquid membrane technology for the separation of racemic mixtures. Journal of Membrane Science,1996,113:351～ 360
[96]王珍,陈晓青,焦飞鹏等.双水相手性萃取拆分扁桃酸外消旋体.分析科学学报,2009,25(5)：507～511
[97]Szekely E, Bansaghi G, Thorey P, et al. Environmentally Benign Chiral Resolution of trans-1,2-Cyclohexanediol by Two-Step Supercritical Fluid Extraction. Industrial & Engineering Chemistry Research,2010,49:9349～9354
[98]Wasewar K L, Yawalkar A A, Moulijn J A, et al. Fermentation of Glucose to Lactic Acid Coupled with Reactive Extraction:A Review. Industrial & Engineering Chemistry Research,2004,43 (19),5969～5982.
[99]Recuero V, Ferrero M, Goror-Fernandez V, et al. Enzymatic resolution of hindered cyanohydrins, key precursors of muscarinic receptor antagonists. Tetrahedron:Asymmetry,2007,18:994～1002
[100]Imai T, Nomura T, Otagiri M. Probenecid-induced changes in the clearance of pranoprofen enantiomers. Chirality.2003,15(4):318～323
[101]Imai T, Nomura T, Aso M, et al. Enantiospecific disposition of pranoprofen in beagle dogs and rats. Chirality.2003,15(4):312～317
[102]Williams K, Day R, Knihinicki R, et al. The stereoselectiv uptake of ibuprofen enantiomers into adipose tissue. Biochemical Pharmacology,1986,35(19):3403～ 3405
[103]Yang Y, Su B, Yan Q, et al. Separation of naproxen enantiomers by supercritical/ subcritical fluid chromatography. Journal of Pharmaceutical and Biomedical Analysis, 2005,39(3-4):815～818
[104]De Haan A B, Simandi B. Extraction Technology for the Separation of Optical Isomers. In:Marcus Y, Sharma M M, Marinsky J A, eds. Ion Exchange and Solvent Extraction. New York:Marcel Dekker Inc.,2001.255～294
[105]Pickering P J, Chaudhuri J B. Equilibrium and kinetic studies of the enantioselective complexation of D/L-phenylalanine with copper (Ⅱ) N-decyl-(L)-hydroxyproline Chemical Engineering Science,1997,52(3):377～386.
[106]Steensma M, Kuipers N J M, de Haan A B, et al. Influence of process parameters on extraction equilibria for the chiral separation of amines and amino-alcohols with a chiral crown ether. Journal of Chemical Technology and Biotechnology,2006,81:588～597
[107]Steensma M, Kuipers N J M, de Haan A B, et al. Analysis and optimization of enantioselective extraction in a multi-product environment with a multistage equilibrium model. Chemical Engineering and Processing:Process Intensification, 2007,46(10):996～1005
[108]Viegas R M C, Afonso C A M, Crespo J G, et al. Modelling of the enantio-selective extraction of propranolol in a biphasic system. Separation and Purification Technology,2007,53:224～234
[109]Miyamoto E, Kawashima S, Murata Y, et al. Physico-chemical Properties of Oxybutynin. Analyst,1994,119:1489～1492
[110]Masson M, Sigurdardottir B V, Matthiasson K, et al. Investigation of Drug-Cyclodextrin Complexes by a Phase-Distribution Method:Some Theoretical and Practical Considerations. Chemical & Pharmaceutical Bulletin,2005,53(8): 958-964
[111]Illapakurthya A C, Wyandta C M, Stodghill S P. Isothermal titration calorimetry method for determination of cyclodextrin complexation thermodynamics between artemisinin and naproxen under varying environmental conditions. European Journal of Pharmaceutics and Biopharmaceutics 2005,59:325～332
[112]Junquera E, Aicart E. A fluorimetric, potentiometric and conductimetric study of the aqueous solutions of naproxen and its association with hydroxypropyl-β-cyclodextrin. International Journal of Pharmaceutics 1999,176:169～178
[113]Zia V, Rajewski R A, Stella V J. Effect of Cyclodextrin Charge on Complexation of Neutral and Charged Substrates:Comparison of (SBE)7M-β-CD to HP-β-CD. Pharmaceutical Research,2001,18(5):667～673
[114]温清,贺坤,郭瑞臣.盐酸奥昔布宁临床应用进展.中国药事,2004,18(7)：445～447
[115]Walker T A. The ciral separation of oxybutnin enantiomers using an ovomucoid column. Journal of Liquid Chromatography & Related Technologies,2000,23:841～ 853
[116]Miyamoto E, Demizu Y, Murata Y, et al. High-performance liquid chromatographic preparation of oxybutynin enantiomers on a chiral stationary phase. Journal of Chromatography:A,1993,653:135～137
[117]郭娜,高新星,徐国防等.高效液相色谱手性流动相添加法拆分奥昔布宁对映体.色谱,2008,26(2)：259～261
[118]高立娣,孙鹏,李秋芳等.奥昔布宁对映体与羟丙基-环糊精选择性缔合的毛细管电泳法分离.应用化学,2009,26(8)：1002～1004
[119]金荣庆,张海波,孟霆等.普拉洛芬的合成研究改进.精细化工中间体,2009,39(3)：37～41
[120]Fukushima T, Santa T, Homma H, et al. Enantiomeric Separation and Detection of 2-Arylpropionic Acids Derivatized with [(N,N-Dimethylamino)sulfonyl] benzofurazan Reagents on a Modified Cellulose Stationary Phase by High-Performance Liquid Chromatography. Analytical Chemistry,1997,69(9): 1793-1799
[121]Van Overbeke A, Baeyens W, Oda H, et al. Direct enantiomeric HPLC separation of several 2-arylpropionic acids, barbituric acids and benzodiazepines on chiralcel OJ-R chiral stationary phase. Chromatographia.1996,43(11-12):599～606
[122]Aboul-Enein H Y, El-Awady M I, Heard C M. Thin layer chromatographic resolution of some 2-arylpropionic acid enantiomers using L-(-)-serine, L-(-)-threonine and a mixture of L-(-)-serine and L-(-)-threonine-impregnated silica gel as stationary phases. Biomedical Chromatography,2003,17(5):325～334
[123]Hayamizu T, Kudoh S, Nakamura H. Methylated N-epsilon-dansyl-L-lysine as a fluorogenic reagent for the chiral separation of carboxylic acid. J. Chromatography B: Biomedical Sciences and Applications,1998,710(1-2):211～218
[124]Ducret A, Trani M, Pepin P. Chiral high performance liquid chromatography resolution of ibuprofen esters. Journal of Pharmaceutical and Biomedical Analysis, 1998,16(7):1225～1231
[125]Steijger O M, Kamminga D A, Lingeman H, et al. An acridinium sulphonylamide as a new chemiluminescent label for the determination of carboxylic acids in liquid chromatography. Journal of Bioluminescence and Chemiluminescence, 1998,13(1):31～40
[126]张振中,蒋红丽,吴逸明.高效毛细管电泳拆分布洛芬对映异构体.中国药科大学学报,1998,29(4)：278～280
[127]Aturki Z, Desiderio C, Mannia L, et al. Chiral separations by capillary zone electrophoresis with the use of cyanoethylated-β-cyclodextrin as chiral selector. Journal of Chromatography A,1998,817(1-2):91～104
[2]Steensma M. Chiral separation of amino-alcohols and amines by fractional reactive extraction:[Thesis]. Enschede, Netherlands:University of Twente,2005
[3]Hutt A J. Drug chirality:impact on pharmaceutical regulation. Chirality,1991,3: 161～164.
[4]郭莉娜,侯仲轲,陈灿等.不对称催化反应合成手性药物的研究进展.精细化工中间体,2006,36(2)：1～4.
[5]尤启冬,林国强.手性药物.北京：化学工业出版社,2004.3～5
[6]French A N. Clean, green chiral reactions-Just Add a Salt. Science,2010, 328(5984):1365～1366.
[7]Dondoni A, Massi A. Asymmetric Organocatalysis:From Infancy to Adolescence. Angewandte Chemie International Edition,2008,47(25):4638～4660
[8]MacMillan D W C. Commentary The advent and development of organocatalysis. Nature,2008455,304～308
[9]Knowles W S. L-Dopa process and intermediates. US Patent,4005127, 1977-01-25
[10]Glueck D S. Catalytic Asymmetric Synthesis of Chiral Phosphanes. Chemistry A European Journal,2008,14(24):7108～7117
[11]Zuend S J, Coughlin M P, Lalonde M P, et al. Scaleable catalytic asymmetric Strecker syntheses of unnatural a-amino acids. Nature,2009,461:968～970
[12]Kwiatkowski P, Beeson T D, Conrad J C, et al. Enantioselective Organocatalytic a-Fluorination of Cyclic Ketones. Journal of the American Chemical Society,2011, 133(6):1738～1741
[13]Cannon J S, Kirsch S F, Overman L E. Catalytic Asymmetric Synthesis of Chiral Allylic Esters. Journal of the American Chemical Society,2010,132 (43):15185～ 15191
[14]Gridnev I D, Watanabe M, Wang H, et al. Mechanism of Enantioselective C-C Bond Formation with Bifunctional Chiral Ru Catalysts:NMR and DFT Study. Journal of the American Chemical Society,2010,132(46):16637～16650
[15]Maier N M, Franco P, Lindner W. Separation of enantiomers:needs, challenges, perspectives. Journal of Chromatography:A,2001,906(1-2):3～33
[16]Srinivas N R, Barbhaiya R H, Midha K K. Enantiomeric drug development: Issues, considerations, and regulatory requirements. Journal of Pharmaceutical Sciences,2001,90(9):1205～1215
[17]Ward T J, Baker B A. Chiral Separations. Analytical Chemistry,2008,80 (12): 4363～4372
[18]D'Oria E, Karamertzanis P G, Price S L. Spontaneous Resolution of Enantiomers by Crystallization:Insights from Computed Crystal Energy Landscapes. Crystal Growth & Design,10(4):1749～1756
[19]Wood W M L. Crystal science techniques in the manufacture of chiral compounds. In:Collins A N, Sheldrake G N, Crosby J, eds. Chirality in Industry II. John Wiley &Sons Inc.,1997.119～115
[20]Bhushan R, Tanwar S. Direct TLC resolution of atenolol and propranolol into their enantiomers using three different chiral selectors as impregnating reagents. Biomedical Chromatography,2008,22(9):1028～1034
[21]朱全红,马果东,邓芹英.薄层色谱用苯基异氰酸酯衍生化的伊环糊精键合固定相的制备及应用.分析化学,2000,28(3)：349～352
[22]Bhushan R, Parshad Vineeta. Resolution of (±)-ibuprofen using L-arginine-impregnated thin-layer chromatography. Journal of Chromatography:A,1996,721(2): 369～372
[23]Bertrand M, Chabin A, Brack A, et al. Separation of amino acid enantiomers VIA chiral derivatization and non-chiral gas chromatography. Journal of Chromatography: A,2008,1180(1-2):131～137
[24]Shamoto T, Tasaki Y, Okada T. Chiral ice chromatography. Journal of the American Chemical Society,2010,132(38):13135～13137
[25]Bhushan R, Kumar V. Indirect resolution of baclofen enantiomers from pharmaceutical dosage form by reversed-phase liquid chromatography after derivatization with Marfey's reagent and its structural variants. Biomedical Chromatography,2008,22(8):906～911
[26]Karthikeyan K, Arularasu G. T, Ramadhas R, et al. Development and validation of indirect RP-HPLC method for enantiomeric purity determination of D-cycloserine drug substance. Journal of Pharmaceutical and Biomedical Analysis,2011,54(4): 850～854
[27]Ilisz I, Berkecz R, Peter A. Application of chiral derivatizing agents in the high-performance liquid chromatographic separation of amino acid enantiomers:A review. Journal of Pharmaceutical and Biomedical Analysis,2008,47(1):1～15
[28]Ameyibor E, Stewart J T. Enantiomeric HPLC Separation of Selected Chiral Drugs Using Native and Derivatized β-Cyclodextrins as Chiral Mobile Phase Additives. Journal of Liquid Chromatography & Related Technologies,1997,20(6): 855～869
[29]Surapaneni S, Khalil S KW. Resolution of terfenadine enantiomers by reversed phase-high performance liquid chromatography using β-cyclodextrin as mobile phase additive. Journal of Pharmaceutical and Biomedical Analysis,1996,14:1631～1634
[30]Van Overbeke A, Baeyens W, Oda H, et al. Direct Enantiomeric HPLC Separation of Several 2-Arylpropionic Acids, Barbituric Acids and Benzodiazepines on Chiralcel OJ-R Chiral Stationary Phase. Chromatographia,1996,43(11-12):599～ 606
[31]Hoffmann C V, Pell R, Lmmerhofer M, et al. Synergistic Effects on Enantioselectivity of Zwitterionic Chiral Stationary Phases for Separations of Chiral Acids, Bases, and Amino Acids by HPLC. Analytical Chemistry,2008,80 (22): 8780～8789
[32]Rubioa N, Minguillon C. Preparative enantioseparation of (±)-N-(3,4-cis-3-decyl-1,2,3,4-tetrahydrophenanthren-4-yl)-3,5-dinitrobenzamide by centrifugal partition chromatography. Journal of Chromatography:A,2010,1217(8):1183～1190
[33]Gomes P S, Zabkova M, Zabka M, et al. Separation of chiral mixtures in real SMB units:The Flex SMB-LSRE. AIChE Journal,2010,56(1):125～142
[34]Petersson P, Markides K E. Chiral separation performed by supercritical fluid chromatography. Journal of Chromatography:A,1994,666(1-2):381～394
[35]Taylor L T. Supercritical Fluid Chromatography. Analytical Chemistry,2010,82 (12):4925～4935
[36]Mangelings D, Heyden Y V. Chiral separations in sub-and supercritical fluid chromatography. Journal of Separation Science,2008,31(8):1252～1273
[37]Shamsi S A, Danielson N D. Utility of ionic liquids in analytical separations. Journal of Separation Science,2007,30(11):1729～1750
[38]Stalcup A M. Chiral separations by capillary electrophoresis. Journal of the American Chemical Society,2010,132(24):8525～8526.
[39]Kostal V, Katzenmeyer J, Arriaga E A. Capillary Electrophoresis in Bioanalysis. Analytical Chemistry,2008,80 (12):4533～4550
[40]Juvancz Z, Kendrovics R B, Ivanyi R, et al. The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis,2008,29(8):1701～1712
[41]Zhang Z, Wu R, Wu M, et al. Recent progress of chiral monolithic stationary phases in CEC and capillary LC. Electrophoresis,2010,31(9):1457～1466
[42]Martinez-Giron A B, Crego A L, Gonzalez M J, et al. Enantiomeric separation of chiral polycyclic musks by capillary electrophoresis:Application to the analysis of cosmetic samples. Journal of Chromatography:A,2010,1217(7):1157～1165
[43]Lau S Y, Uzir M H, Kamaruddin A H, et al. Lipase-catalyzed dynamic kinetic resolution of racemic ibuprofen ester via hollow fiber membrane reactor:Modeling and simulation. Journal of Membrane Science,2010,357(1-2):109～121.
[44]Lau S Y, Gonawan F N, Subhash B, et al. Conceptual design and simulation of a plant for the production of high purity (S)-ibuprofen acid using innovative enzymatic membrane technology. Chemical Engineering Journal,2011,166(2):726-737
[45]Miyako E, Maruyama T, Kamiya F, et al. Highly enantioselective separation using a supported liquid membrane encapsulating surfactant-enzyme complex. Journal of the American Chemical Society,2004,126(28):8622～8623
[46]Krieg H M, Lotter J, Keizer K, et al. Enrichment of chlorthalidone enantiomers by an aqueous bulk liquid membrane containing β-cyclodextrin. Journal of Membrane Science,2000,167(1):33～45
[47]Rmaile H H, Schlenoff J B. Optically active polyeletrolyte multilayers as membranes for chiral separations. Journal of the American Chemical Society,2003, 125(22):6602-6603
[48]Yoshikawa M, Murakoshi K, Kogita T, et al. Chiral separation membranes from modified polysulfone having myrtenal-derived terpenoid side groups. European Polymer Journal,2006,42(10):2532-2539
[49]唐课文,周春山,蒋新宇.支载液膜双有机相萃取分离氧氟沙星外消旋体.中国科学(B),2002,32(6)：491-496
[50]姚传义,张金红,俞耀庭.酶法手性化合物的合成与拆分.化工进展,2000,19(6)：35-50
[51]Bhushan I, Parshad R, Qazi G N, et al. Lipase enzyme immobilization on synthetic beaded macroporous copolymers for kinetic resolution of chiral drugs intermediates. Process Biochemistry,2008,43(4):321-330
[52]Abergel R J, Zawadzka A M, Hoette T M, et al. Enzymatic Hydrolysis of Trilactone Siderophores:Where Chiral Recognition Occurs in Enterobactin and Bacillibactin Iron Transport(1). Journal of the American Chemical Society,2009,131 (35):12682～12692
[53]Van Tol J, Bert A, Duine J, et al. Description of hydrolase enantioselectivity must be based on the actual kinetic resolution of glycidyl(2,3-epoxy-l-propyl) butyrate by pig pancreas lipase. Biocatalysis and Biotransformation,1995,12(2):99-117
[54]Pellissier H. Recent developments in dynamic kinetic resolution. Tetrahedron, 2008,64(8):1563～1601
[55]Schuur B, Verkuijl B J V, Minnaard A J, et al. Chiral separation by enantioselective liquid-liquid extraction. Organic & Biomolecular Chemistry,2011,9: 36～51
[56]Steensma M, Kuipers N J M, de Haan A B, et al. Modelling and experimental evaluation of reaction kinetics in reactive extraction for chiral separation of amines, amino acids and aminoalcohols. Chemical Engineering Science,2007,62(5):1395～ 1407
[57]Bowman N S, McCloud G T, Schweitzer G K. Partial resolution of some organic racemates by solvent extraction. Journal of the American Chemical Society,1968, 90(14):3848～3852
[58]Schweitz, G K, Supernaw I R, Bowman N S J. The solvent extraction resolution of some optically-active neutral chelates. Journal of Inorganic and Nuclear Chemistry, 1968,30(7):1885～1887
[59]Molnar P, Thorey P, Bansaghi G, et al. Resolution of racemic trans-1,2-cyclohexanediol with tartaric acid. Tetrahedron:Asymmetry,2008, (19): 1587～1592
[60]Tan B, Luo G S, Wang J D. Extraction separation of amino acid enantiomers with co-extractions of tartaric acid derivative and Aliquat-336. Separation and Purification Technology,2007,53(3):330～336
[61]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.应用化学,2003,11(20)：1108～1110
[62]唐课文,周春山.疏水性L酒石酸酯立体选择性萃取分离氯噻酮对映体.分析化学,2004,32(1)：63～66
[63]唐课文,周春山.疏水性相转移手性溶剂萃取分离叔丁喘宁对映体.分析化学,2004,3(32)：278～282
[64]唐课文,陈国斌,周春山.手性配体立体选择性萃取分离扁桃酸对映体.无机化学学报,2004,3：339～344
[65]唐课文,周春山,蒋新宇.支载液膜双有机相萃取分离氧氟沙星外消旋体[J]. 中国科学(B),2002,32(6)：491～496
[66]Nazarenko A Y, Huszthy P, Bradshaw J S, et al. Journal of Inclusion Phenomena and Macrocyclic Chemistry,1995,20(1) 13～22
[67]Newcomb M, Toner J L, Helgeson R C, et al. Host-guest complexation.20. Chiral recognition in transport as a molecular basis for a catalytic resolving machine. Journal of the American Chemical Society,1979,101(17):4941～4947
[68]Peacock S C, Domeier L A, Gaeta F C A, et al. Host-guest complexation.13. High chiral recognition of amino esters by dilocular hosts containing extended steric barriers. Journal of the American Chemical Society,1978,100(26):8190～8202
[69]Takeuchi T, Horikawa R, Tanimura T. Enantioselective solvent extraction of neutral DL-amino acids in two-phase systems containing N-n-alkyl-L-proline derivatives and copper(Ⅱ) ion. Analytical Chemistry,1984,56 (7):1152～1155
[70]Koska J, Haynes C A. Modelling multiple chemical equilbria in chiral partition systems. Chemical Engineering Science,2001,56:5853～5864
[71]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. Journal of Organic Chemistry,2009,74(17):6526～6533
[72]Hallett A J, Kwant G J, de Vries J G. Continuous Separation of Racemic 3,5-Dinitrobenzoyl-Amino Acids in a Centrifugal Contact Separator with the Aid of Cinchona-Based Chiral Host Compounds. Chemistry A European Journal,2009,15: 2111～2120
[73]Kellner K H, Blasch A, Chmiel H, et al. Enantioseparation of N-Protected Alpha-Amino Acid Derivatives by Liquid-Liquid Extraction Technique Employing Stereoselective Ion-Pair Formation With a Carbamoylated Quinine Derivative. Chirality,1997,9(3):268～273
[74]Maier N M, Schefzick S, Lombardo G M, et al. Elucidation of the Chiral Recognition Mechanism of Cinchona Alkaloid Carbamate-Type Receptors for 3,5-Dinitrobenzoyl Amino Acids. Journal of the American Chemical Society,2002, 124(29):8611～8629
[75]Schuur B, Winkelmam J G M, Heeres H J. Equilibrium studies on enantioselective liquid-liquid amino acid extraction using a cinchona alkaloid extractant. Industrial & Engineering Chemistry Research,2008,47:10027～10033
[76]陈慧,王孙琴.环糊精类高效液相色谱固定相的研究进展.色谱,1999,17(6)：533～538
[77]刘育,尤长城,张衡益.超分子化学：合成受体的分子识别与组装.天津：南开大学出版社.2001,166～169
[78]Armstrong D W, Ward T J, Armstrong R J, et al. Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes. Science, 1986,232(4754):1132～1135
[79]Escandadr G M. Spectroscopic study of sadlicylate-cyclodextrin systems in the presence and absence of alcohols. Spectrochimica Acta, Part A:Molecular Spectroscopy,1999,55(9):1743～1752
[80]Szeman J, Ganzler K, Salgo A, et al. Effect of the degree of substitution of cyclodextrin derivatives on chiral separations by high-performance liquid chromatography and capillary electrophoresis. Journal of Chromatography: A,1996, 728(1-2):423～431
[81]Koppenhoefer B, Eppedein U, Christian B, et al. Separation of enatiomers of drugs by capillary electrophoresis Ⅲ.β-cyclodextrin as chiral solvating agent. Journal of Chromatography:A,1996,735(1-2):333～343
[82]Liu Y, Song Y, Wang H, et al. Selective Binding of Steroids by 2,2'-Biquinoline-4,4'-dicarboxamide-Bridged Bis((3-cyclodextrin):Fluore-scence Enhancement by Guest Inclusion. Journal of Organic Chemistry,2003,68(9):3687～3690
[83]Liu Y, Li X Q, Chen Y, et al. Spectrophotometric Study of Selective Binding Behaviors of Dye Molecules by Pyridineand Bipyridine-Modified β-Cyclodextrin Derivatives with a Functional Tether in Aqueous Solution. Journal of Physical Chemistry B,2004,108(50):19541～19549
[84]Venema F, Nelissen H F M, Berthault P, et al. Synthesis, Conformation, and Binding Properties of Cyclodextrin Homo- and Heterodimers Connected through Their Secondary Sides. Chemistry A European Journal,1998,4(11):2237～2250
[85]Jiao F P, Chen X Q, Hu W G, et al. Enantioselective extraction of mandelic acid enantiomers by L-dipentyl tartrate and beta-cyclodextrin as binary chiral selectors. Chemical Papers,2007,61(4):326～328
[86]Tang K, Chen Y, Huang K, et al. Enantioselective Resolution of chiral aromatic acids by biphasic recognition chiral extraction. Tetrahedron:Asymmetry,2007,18: 2399～2408
[87]Nishizawa H, Tahara K, Hayashida A, et al. Continuous Separation Method with Liquid Particle Extractor:Enantioseparation of (±)-Mandelic Acid. Analytical Sciences,1993,9(5):611～615
[88]Tang K, Miao J, Liu Y, et al. Equilibrium Studies on Reactive Extraction of α-Cyclohexyl-mandelic Enantiomers Using Hydrophilic β-Cyclodextrin Derivatives Extractants. Chinese Journal of Chemistry 2010,28(8):1444～1450
[89]Tang K, Miao J, Zhou T, et al. Reaction kinetics in reactive extraction for chiral separation of a-cyclohexyl-mandelic acid enantiomers with hydroxypropyl-β-cyclodextrin. Chemical Engineering Science,2011,66(3):397～404
[90]Tang K, Miao J, Zhou T, et al. Equilibrium studies on reactive extraction of naproxen enantiomers using hydrophilic β-cyclodetrin derivatives extractants. Journal of Inclusion Phenomena and Macrocyclic Chemistry,2010,69(1-2):213～220
[91]Erdal K, Aysegul K, Abdulkadir S. Synthesis of new chiral calix[4]arene diamide derivatives for liquid phase extraction of a-amino acid methylesters. Tetrahedron: Asymmetry,2006,17(10):1514～1520
[92]Davis A P, Lawless L J. Steroidal guanidinium receptors for the enantioselective recognition of N-acyl-α-amino acids. Chemical Communications.1999, (1),9～10.
[93]Davis, J. T. G-Quartets 40 Years Later:From 5'-GMP to Molecular Biology and Supramolecular Chemistry. Angewandte Chemie, International Edition,2004,43(6): 668～698
[94]Tang K, Yi J, Liu Y, et al. Enantioselective separation of R,S-phenylsuccinic acid by biphasic recognition chiral extraction. Chemical Engineering Science,2009,64: 4081～4088
[95]Keurentjes J T F, Nabuurs L W M, Vegter E A. Liquid membrane technology for the separation of racemic mixtures. Journal of Membrane Science,1996,113:351～ 360
[96]王珍,陈晓青,焦飞鹏等.双水相手性萃取拆分扁桃酸外消旋体.分析科学学报,2009,25(5)：507～511
[97]Szekely E, Bansaghi G, Thorey P, et al. Environmentally Benign Chiral Resolution of trans-1,2-Cyclohexanediol by Two-Step Supercritical Fluid Extraction. Industrial & Engineering Chemistry Research,2010,49:9349～9354
[98]Wasewar K L, Yawalkar A A, Moulijn J A, et al. Fermentation of Glucose to Lactic Acid Coupled with Reactive Extraction:A Review. Industrial & Engineering Chemistry Research,2004,43 (19),5969～5982.
[99]Recuero V, Ferrero M, Goror-Fernandez V, et al. Enzymatic resolution of hindered cyanohydrins, key precursors of muscarinic receptor antagonists. Tetrahedron:Asymmetry,2007,18:994～1002
[100]Imai T, Nomura T, Otagiri M. Probenecid-induced changes in the clearance of pranoprofen enantiomers. Chirality.2003,15(4):318～323
[101]Imai T, Nomura T, Aso M, et al. Enantiospecific disposition of pranoprofen in beagle dogs and rats. Chirality.2003,15(4):312～317
[102]Williams K, Day R, Knihinicki R, et al. The stereoselectiv uptake of ibuprofen enantiomers into adipose tissue. Biochemical Pharmacology,1986,35(19):3403～ 3405
[103]Yang Y, Su B, Yan Q, et al. Separation of naproxen enantiomers by supercritical/ subcritical fluid chromatography. Journal of Pharmaceutical and Biomedical Analysis, 2005,39(3-4):815～818
[104]De Haan A B, Simandi B. Extraction Technology for the Separation of Optical Isomers. In:Marcus Y, Sharma M M, Marinsky J A, eds. Ion Exchange and Solvent Extraction. New York:Marcel Dekker Inc.,2001.255～294
[105]Pickering P J, Chaudhuri J B. Equilibrium and kinetic studies of the enantioselective complexation of D/L-phenylalanine with copper (Ⅱ) N-decyl-(L)-hydroxyproline Chemical Engineering Science,1997,52(3):377～386.
[106]Steensma M, Kuipers N J M, de Haan A B, et al. Influence of process parameters on extraction equilibria for the chiral separation of amines and amino-alcohols with a chiral crown ether. Journal of Chemical Technology and Biotechnology,2006,81:588～597
[107]Steensma M, Kuipers N J M, de Haan A B, et al. Analysis and optimization of enantioselective extraction in a multi-product environment with a multistage equilibrium model. Chemical Engineering and Processing:Process Intensification, 2007,46(10):996～1005
[108]Viegas R M C, Afonso C A M, Crespo J G, et al. Modelling of the enantio-selective extraction of propranolol in a biphasic system. Separation and Purification Technology,2007,53:224～234
[109]Miyamoto E, Kawashima S, Murata Y, et al. Physico-chemical Properties of Oxybutynin. Analyst,1994,119:1489～1492
[110]Masson M, Sigurdardottir B V, Matthiasson K, et al. Investigation of Drug-Cyclodextrin Complexes by a Phase-Distribution Method:Some Theoretical and Practical Considerations. Chemical & Pharmaceutical Bulletin,2005,53(8): 958-964
[111]Illapakurthya A C, Wyandta C M, Stodghill S P. Isothermal titration calorimetry method for determination of cyclodextrin complexation thermodynamics between artemisinin and naproxen under varying environmental conditions. European Journal of Pharmaceutics and Biopharmaceutics 2005,59:325～332
[112]Junquera E, Aicart E. A fluorimetric, potentiometric and conductimetric study of the aqueous solutions of naproxen and its association with hydroxypropyl-β-cyclodextrin. International Journal of Pharmaceutics 1999,176:169～178
[113]Zia V, Rajewski R A, Stella V J. Effect of Cyclodextrin Charge on Complexation of Neutral and Charged Substrates:Comparison of (SBE)7M-β-CD to HP-β-CD. Pharmaceutical Research,2001,18(5):667～673
[114]温清,贺坤,郭瑞臣.盐酸奥昔布宁临床应用进展.中国药事,2004,18(7)：445～447
[115]Walker T A. The ciral separation of oxybutnin enantiomers using an ovomucoid column. Journal of Liquid Chromatography & Related Technologies,2000,23:841～ 853
[116]Miyamoto E, Demizu Y, Murata Y, et al. High-performance liquid chromatographic preparation of oxybutynin enantiomers on a chiral stationary phase. Journal of Chromatography:A,1993,653:135～137
[117]郭娜,高新星,徐国防等.高效液相色谱手性流动相添加法拆分奥昔布宁对映体.色谱,2008,26(2)：259～261
[118]高立娣,孙鹏,李秋芳等.奥昔布宁对映体与羟丙基-环糊精选择性缔合的毛细管电泳法分离.应用化学,2009,26(8)：1002～1004
[119]金荣庆,张海波,孟霆等.普拉洛芬的合成研究改进.精细化工中间体,2009,39(3)：37～41
[120]Fukushima T, Santa T, Homma H, et al. Enantiomeric Separation and Detection of 2-Arylpropionic Acids Derivatized with [(N,N-Dimethylamino)sulfonyl] benzofurazan Reagents on a Modified Cellulose Stationary Phase by High-Performance Liquid Chromatography. Analytical Chemistry,1997,69(9): 1793-1799
[121]Van Overbeke A, Baeyens W, Oda H, et al. Direct enantiomeric HPLC separation of several 2-arylpropionic acids, barbituric acids and benzodiazepines on chiralcel OJ-R chiral stationary phase. Chromatographia.1996,43(11-12):599～606
[122]Aboul-Enein H Y, El-Awady M I, Heard C M. Thin layer chromatographic resolution of some 2-arylpropionic acid enantiomers using L-(-)-serine, L-(-)-threonine and a mixture of L-(-)-serine and L-(-)-threonine-impregnated silica gel as stationary phases. Biomedical Chromatography,2003,17(5):325～334
[123]Hayamizu T, Kudoh S, Nakamura H. Methylated N-epsilon-dansyl-L-lysine as a fluorogenic reagent for the chiral separation of carboxylic acid. J. Chromatography B: Biomedical Sciences and Applications,1998,710(1-2):211～218
[124]Ducret A, Trani M, Pepin P. Chiral high performance liquid chromatography resolution of ibuprofen esters. Journal of Pharmaceutical and Biomedical Analysis, 1998,16(7):1225～1231
[125]Steijger O M, Kamminga D A, Lingeman H, et al. An acridinium sulphonylamide as a new chemiluminescent label for the determination of carboxylic acids in liquid chromatography. Journal of Bioluminescence and Chemiluminescence, 1998,13(1):31～40
[126]张振中,蒋红丽,吴逸明.高效毛细管电泳拆分布洛芬对映异构体.中国药科大学学报,1998,29(4)：278～280
[127]Aturki Z, Desiderio C, Mannia L, et al. Chiral separations by capillary zone electrophoresis with the use of cyanoethylated-β-cyclodextrin as chiral selector. Journal of Chromatography A,1998,817(1-2):91～104