厚体液膜和泡沫分馏技术拆分药物对映体的应用及其机理研究
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摘要
本文研究了手性流动相添加法拆分手性药物的分析方法及其热力学性质,分别用厚体液膜技术和泡沫分馏技术拆分扁桃酸对映体和蛋氨酸对映体,研究了各因素对拆分效果的影响,并对拆分机理进行了初步探讨。
(1)分析方法的建立。采用手性流动相添加法建立了扁桃酸和氧氟沙星手性分析方法,手性固定相法为蛋氨酸建立手性分析方法,分别确定各药物对映体最适宜的分析条件。
(2)手性流动相添加剂法拆分氧氟沙星对映体的热力学性质研究。在C18高效液相色谱柱上,以L-苯丙氨酸和硫酸铜为手性配体流动相,在温度293～313K范围内,考察了氧氟沙星对映体的保留和分离行为。在实验范围内,温度升高对分离不利,随着温度的升高,对映体的保留时间、分离度和选择性因子均减少。通过对拆分中焓变、焓变差值和熵变差值等热力学参数的计算,确定在所测温度范围内其手性拆分过程为焓控过程。
(3)厚体液膜技术拆分扁桃酸对映体。以D2EHPA和L-(-)-DBTA二元手性载体,正辛醇为膜溶剂,采用厚体液膜法拆分了扁桃酸外消旋体。考察了拆分时间、各物质浓度比、搅拌转速、反应温度各参数对拆分的影响,得到最佳拆分条件:拆分时间4h,C_(MA):C_(D2EHPA):C_(L-(-)-DBTA)=0.05:0.2:0.3,搅拌转速400r/min,反应温度35℃,此时得到最大分离因子2.74,对映体过剩值46.47%。
(4)泡沫分馏技术拆分蛋氨酸对映体。采用泡沫分馏技术,分别用不同的手性捕收剂分离扁桃酸对映体和蛋氨酸对映体。主要考察手性捕收剂的筛选、捕收剂/手性药物质量浓度比、回流时间、空气流速、分馏柱填料层高度及溶液pH值对拆分性能的影响,并使用正交实验法考察了各因素对蛋氨酸外消旋体的拆分影响,通过正交实验方差分析发现回流气速和样品溶液中组分浓度比两个因素对泡沫分馏法拆分手性药物的效果影响较大。
In this paper,the establishment of analytical methods about separation of chiral drugs and their thermodynamic properties of chiral mobile phase addition(CMPA) method were investigated.Additionally mandelic acid enantiomers and methionine enantiomers were separated by the techniques of bulk liquid membrane and foam fractionation respectively,while the influencing factors of separation and the separation mechanism was also discussed.
(1) Establishment of analytical methods.The chiral analysis methods were established for mandelic acid and ofloxacin by CMPA and methionine by chiral stationary phase,respectively.Furthermore,the optimal conditions for enantiomeric analysis was confirmed.
(2) Investigation of the thermodynamic properties of resolution of ofloxacin enantiomers by CMPA.The effect of temperature(293～313K) on chromatographic separation of ofloxacin over a C18 column was investigated with L-phenylalanine-CuSO_4 aqueous solution and methanol as the chiral ligand mobile phase.Higher column temperature was found to be disadvantageous to the enantiomer separation for the retention time, resolution and selectivity of the chiral separation were decreased with the increase of temperature.Moreover and very importantly,the enantiomeric separation is a enthalpy controlled process in the examined temperature range by calculation of thermodynamic functions(△H°,△_(S,R)△H°,△_(S,R)△S°).
(3) Resolution of mandelic acid enantiomers by the technique of bulk liquid membrane.A new method of bulk liquid membrane using complex of D2EHPA and L-(-)-DBTA was developed for the resolution of racemic mandelic acid.The influences of time,the concentration ratio of MA,D2EHPA and L-(-)-DBTA,rotated speed and temperature on chiral separation were studied and optimized.The biggest separation factor (α)2.74 and the enantiometric excess value(ee%) 46.47%were obtained when the separation time was 4 hour,the concentration ratio of MA, D2EHPA and L-(-)-DBTA was 0.05:0.2:0.3,the rotated speed was 400r/min and the temperature was 35℃.
(4) Resolution of methionine enantiomers by the technique of foam fractionation.Mandelic acid and methionine enantiomers were separated using different chiral collectors by the technique of foam fractionation. The species of chiral collectors,the concentration ratio of collectors and chiral enantiomers,reflux equilibriation time,gas flow rate,packing height and pH of buffer on resolution performances were investigated, respectively.The effects of different factors on resolution of methionine enantiomers were studied by Orthogonal experiment.After variance analysis,it was found that the influences of reflux equilibriation time and the concentration ratio of sample solution were greater in resolution of methionine enantiomers by the technique of foam fractionation.
(1)分析方法的建立。采用手性流动相添加法建立了扁桃酸和氧氟沙星手性分析方法,手性固定相法为蛋氨酸建立手性分析方法,分别确定各药物对映体最适宜的分析条件。
(2)手性流动相添加剂法拆分氧氟沙星对映体的热力学性质研究。在C18高效液相色谱柱上,以L-苯丙氨酸和硫酸铜为手性配体流动相,在温度293～313K范围内,考察了氧氟沙星对映体的保留和分离行为。在实验范围内,温度升高对分离不利,随着温度的升高,对映体的保留时间、分离度和选择性因子均减少。通过对拆分中焓变、焓变差值和熵变差值等热力学参数的计算,确定在所测温度范围内其手性拆分过程为焓控过程。
(3)厚体液膜技术拆分扁桃酸对映体。以D2EHPA和L-(-)-DBTA二元手性载体,正辛醇为膜溶剂,采用厚体液膜法拆分了扁桃酸外消旋体。考察了拆分时间、各物质浓度比、搅拌转速、反应温度各参数对拆分的影响,得到最佳拆分条件:拆分时间4h,C_(MA):C_(D2EHPA):C_(L-(-)-DBTA)=0.05:0.2:0.3,搅拌转速400r/min,反应温度35℃,此时得到最大分离因子2.74,对映体过剩值46.47%。
(4)泡沫分馏技术拆分蛋氨酸对映体。采用泡沫分馏技术,分别用不同的手性捕收剂分离扁桃酸对映体和蛋氨酸对映体。主要考察手性捕收剂的筛选、捕收剂/手性药物质量浓度比、回流时间、空气流速、分馏柱填料层高度及溶液pH值对拆分性能的影响,并使用正交实验法考察了各因素对蛋氨酸外消旋体的拆分影响,通过正交实验方差分析发现回流气速和样品溶液中组分浓度比两个因素对泡沫分馏法拆分手性药物的效果影响较大。
In this paper,the establishment of analytical methods about separation of chiral drugs and their thermodynamic properties of chiral mobile phase addition(CMPA) method were investigated.Additionally mandelic acid enantiomers and methionine enantiomers were separated by the techniques of bulk liquid membrane and foam fractionation respectively,while the influencing factors of separation and the separation mechanism was also discussed.
(1) Establishment of analytical methods.The chiral analysis methods were established for mandelic acid and ofloxacin by CMPA and methionine by chiral stationary phase,respectively.Furthermore,the optimal conditions for enantiomeric analysis was confirmed.
(2) Investigation of the thermodynamic properties of resolution of ofloxacin enantiomers by CMPA.The effect of temperature(293～313K) on chromatographic separation of ofloxacin over a C18 column was investigated with L-phenylalanine-CuSO_4 aqueous solution and methanol as the chiral ligand mobile phase.Higher column temperature was found to be disadvantageous to the enantiomer separation for the retention time, resolution and selectivity of the chiral separation were decreased with the increase of temperature.Moreover and very importantly,the enantiomeric separation is a enthalpy controlled process in the examined temperature range by calculation of thermodynamic functions(△H°,△_(S,R)△H°,△_(S,R)△S°).
(3) Resolution of mandelic acid enantiomers by the technique of bulk liquid membrane.A new method of bulk liquid membrane using complex of D2EHPA and L-(-)-DBTA was developed for the resolution of racemic mandelic acid.The influences of time,the concentration ratio of MA,D2EHPA and L-(-)-DBTA,rotated speed and temperature on chiral separation were studied and optimized.The biggest separation factor (α)2.74 and the enantiometric excess value(ee%) 46.47%were obtained when the separation time was 4 hour,the concentration ratio of MA, D2EHPA and L-(-)-DBTA was 0.05:0.2:0.3,the rotated speed was 400r/min and the temperature was 35℃.
(4) Resolution of methionine enantiomers by the technique of foam fractionation.Mandelic acid and methionine enantiomers were separated using different chiral collectors by the technique of foam fractionation. The species of chiral collectors,the concentration ratio of collectors and chiral enantiomers,reflux equilibriation time,gas flow rate,packing height and pH of buffer on resolution performances were investigated, respectively.The effects of different factors on resolution of methionine enantiomers were studied by Orthogonal experiment.After variance analysis,it was found that the influences of reflux equilibriation time and the concentration ratio of sample solution were greater in resolution of methionine enantiomers by the technique of foam fractionation.
引文
[1]尤田耙.手性化合物的现代研究方法.合肥:中国科学技术大学出版社,1993
[2]刘凤艳,庞小琳,郑轶群,甘秀石.手性物质及其拆分方法.辽宁化工,2007,36(11):784-786
[3]余兰,江波.手性技术在药物中的应用.遵义医学院学报,2004,27(2):188-192
[4]朱长生.普萘洛尔的合成与拆分研究.湖南工业职业技术学院报,2003,3(3):18-19
[5]Guxman A,Yuste F,Toscano RA,et al.Absolute configuration of(-)-5-benzoyl -1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid,the active enantiomer of ketorolac.J.Med.Chem.,1986,(29):589-594
[6]Mitscher LA,Sharma PN,Chu-Daniel.DNA gyrase inhibitors 2.Asymmetric synthesis and biological activtity of the enantiomers of 9-fluoro-3- methyl-10-(4-methyl-1-piperacinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzox azine-6-carbox Ylic acid(ofloxacin).J.Med.Chem.,1987,30(12):2283-2291
[7]Plenge P,Mellerup ET,Honore T,et al.The activity of 25 paroxetine/femixetine structure variants in various reactions,assumed to be important for the effect of antidepressants.J.Pharm.Pharmcal.,1987,39(11):877-882
[8]杨健,向钰.镇咳药左旋羟苯哌嗪的合成.药物研究,2000,9(3):25-25
[9]Blaschke G,Kaft HP,Fickentscher K,et al.Chromatographic racemic separation of thalidomide and teratogenic activtity of its enantiomers.Arxneim-Farsch.1979,29(10):1640-1649
[10]Goodwin SD,Gallis HA,Chow AT.Phanmacology and safety of levofloxacin in patients with human immunodeficiency virus infection.Antimicrob Aents Chemother,1994,(38):799-805
[11]Tobert JA,Cirillo VJ,Hitsenberger G,et al.Enhancement of uricosuric properties of indacrinone by manipulation of the eantiomer ratio.Clin.Pharmacal.Ther.,1981,29(3):344-353
[12]Gold EH,Chang W,Coben M,et al.Synthesis and comparison of some cardiovascular properties of the stereoisomers of labetalol.Med.Chem.,1982,(25):1363-1369
[13]Michael J.Single enantiomer drugs:new strategies and directions.Chemistry& Industry,1996,5(20):374-378
[14]Miriam L.Membranes make chiral separations simpler.Manufacturing Chemist,1995,10:25-32
[15]Gimenez F,Pennie RA,Crevoisier C.Stereoselective pharmacokinetics of mefl-oquine in healthy caucasinans after multiple does.J.Pharm.Sci.,1994,83(6):824-827
[16]Sylvie L,DidierV,Alain VW,et al.SMB enantioseparation:process development,modeling,and operating conditions.AIChE J.,2000,46(2):247-256
[17]James ER.Chiral separations.AIChE J.,2001,47(1):2-5
[18]Botsaris DG,Qian RY,Barrett A.New insights into nucleation through chiral crystallization.AIChE J.,1999,45(1):201-203
[19]肖畴阡,宋光泉.有机化学.中山大学出版社,1996:196
[20]邓金根,迟永祥,朱懂,蒋耀忠.化学拆分的新方法研究.合成化学,1999,7(4):340-345
[21]Schmid A,Dordick JS.,Kiener A,Wubbolts M,Witholt B,Industrial Biocatalysis today and tomorrow.Nature,2001,409(6817):258-268
[22]周志强,张红雁,于兆文,等.高效液相色谱法对外消旋药物的拆分.分析测试技术与仪器,1998,4(1):1-7
[23]曾苏,章立,沈向忠,等.光学异构体的气相色谱拆分法.色谱,1994,12(4):59-262
[24]谢锐,褚良银,曲剑波.手性拆分膜的研究与应用新进展.现代化工,2004,24(4):15-18
[25]Gabelman A,Hwang S-T.Hollow fiber membrane contactors.J.Membr.Sci.,1999,159:61-106
[26]Vankelecom IFJ,Grobet P,Yoshikawa M,et al.Membranes based on poly(7-methyl-1-glutamate):synthesis,characterization and use in chiral separations.J.Membr.Sci.,2001,186:153-163
[27]Maruyama A,Adachi N,Takasuki T,et al.Enantioselective permeation of α-amino acid isomers through poly(amino acid)-derived membranes.Macromolecule,1990,23:2748-2752
[28]Yashima E,Noguchi J,Okamoto Y.Continuous and preparative enantio separation of Oxprenolol with cellulose Tris(3,5-dimethylphenyl-carbamate) -coated Belt.Tetra.Asymm.,1995,6(8):1889-1890
[29]Yashima E,Noguchi J,Okamoto Y.Enantiomer Enrichment of Oxprenolol through cellulose tris(3,5-dimethylphenylcarbamate)membrane.J.Appl.Polym.Sci.,1994,54:1087-1091
[30]Teruyuki M,Masaharu S,Sersuji T.Optical resolution of amino acid by enantioselective ultrafiltration memberane.J.Chem.Eng.Jpn.,1992,25(1):33-38
[31]Thoelen C,Debryn M,Theunissen E.Membrane based on poly(γ-methyl-L-glutamate):synthesis,characterization and use in chiral separations.J.Membr.Sci.,2001,186:153-163
[32]张瑞华等.液膜分离技术.南昌:江西人民出版社,1984.14-15
[33]Cohoso IM,Cadoso MM,Viegas RMC,et al.Transport mechanisms and modeling in liquid membrane contactors.Sep.Purif.Technol.,2000,19(3):183-197
[34]谭斌,骆广生,元暄.液膜及液膜萃取拆分手性物质的研究进展.现代化工,2005,25,13-15
[35]唐课文,周春山,蒋新宇.支持液膜双有机相萃取分离氧氟沙星外消旋体.中国科学,2002,32(6):491-496
[36]戴荣继,苏彩莲,佟斌.膜拆分法分离制备手性药物.膜科学与技术,2006,26(3):84-88
[37]Pickering PJ,Chaudhuri JB.Enantioselective extraction of(D)-phenylalanine from racemic(D/L)-phenylalanine using chiral emulsion liquid membranes.J.Membr.Sci.,1997,127(2):115-130
[38]Oshima T,Inoue K,Furusaki S,Goto M.Liquid membrane transport of amino acids by a calyx[6]arene carboxylic acid derivative.J.Membr.Sci.,2003,217:87-97
[39]黄可龙,胡卫国,焦飞鹏,苏静.厚体液膜拆分克伦特罗外消旋体及其动力学研究.分析化学研究报告,2007,35(4):479-483
[40]Krieg Henning M,Lotter Jeanette,Keizer Klaas,et al.Enrichment of chlorthalidone enantiomers by an aqueous bulk liquid membrane containing β-cyclodextrin.J.Membr.Sci.,2000,167(1):33-38
[41]刘茉娥,陈欢林.新型分离技术基础.杭州:浙江大学出版社,1993,46
[42]汪德进.泡沫分离技术及其模型的研究进展.安庆师范学院学报(自然科学版),2002,3(13):44-46
[43]董红星,李占双,李凯峰,等.泡沫分离法除去污水中十二烷基苯磺酸纳的研究.应用科技,2003,30(3):48-49
[44]Walling CW,Ruff EE,Thorntn JL.Studies on the Separation of Cadrnium from by Foam Separation.Phys Chem,1957,(61):486-493
[45]Rubin A J,Johnson JD,Lamb JC.Comparison of Variables in Ion and Precipitate Flotation.Eng.Chem.Process Des.Dev.,1996,(5):368-372
[46]Yun-Hwei Shen.Colloidal titanium dioxide sepasration from water by foam flotation.Sep.Sci.tech.,1998,33(16):2623-2635
[47]Chien-shu Luo,Shang-da Huang.Removal of Copper from aqueous ammine Copper(Ⅱ) Solution by foam flotation.Sep.Sci.tech.,1993,28(7):1395-1418
[48]Koutlemani MM,Mavros P,Zouboulis AI.Recovery of Co~(2+) Ions from Aqueous Solutions by Forth Flotation.Sep.Sci.tech.,1994,29(7):867-888
[49]Moussavi Mobsen.Separation of cyanide ions by foam fractionation.Sep.Sci.tech.,1992,27(6):783-792
[50]Wingrattansopon Pukpong,Seamenom John and Charedj sumecth et al.Biosrptive Flotation in Metal Ions Recovery.Sep.Sci.tech.,1987,22(11):1523-1540
[51]严希康,潇涣华.用基于表面活性剂的分离方法提取庆大霉素Ⅰ:泡沫分离法.中国抗生素杂志,1996,21(4):256-259
[52]陈树晖,褚家瑛,江体乾.泡沫分离技术的实验研究--回收废液中的金.化工学报,1991,34(6):770-774
[53]刘志红,刘铮,丁富新.用饱沫分离法浓缩和分离蛋白质Ⅰ.清华大学学报,1997,37(12):50-54
[54]管志远,丁爱民,沈宏,等.环流气浮分离技术在含Ni(Ⅱ)废水处理中的试验.高校化学工程学报,1998,12(3):293-297
[55]王绢,褚家瑛.泡沫塔吸附分离BF~(4-).化工学报,1994,45(3):380-384
[56]周长春,刘炯天,周志坚.泡沫浮选在生化分离技术中的应用.选煤技术,2002,6:17-21
[57]J.赖亚.泡沫浮选表面化学.北京:冶金工业出版社,1987:88-128
[58]陈欢林.新型分离技术.北京:化学工业出版社,2005:295-310
[59]陈敏恒,丛德滋,方图南.化工原理.北京:化学工业出版社,1986:67-75
[60]Armstrong DW,Schneiderheinze JM,Hwang YS.Bubble fractionation of enantiomers from solution using molecularly imprinted polymers as collectors.Anal.Chem.,1998,70:3717-3719
[61]刘良.扁桃腈和扁桃酸的技术进展.精细化工化纤信息通讯,2002,1:6-6
[62]Arai T,Koike H,K(?)ji H,(?)izumi H.Separation of pyridone carboxylic acid Enantiomers by high-performance liquid chromatography using copper(Ⅱ)-L- amino acid as the eluent.J.Chromatogr.,1988,448:439-444
[63]Rosa HH,Pilar CF.Chromatographic separation of chlorthalidone Enantiomers using β-cyclodextrins as chiral additives.J.Chromatogr.B,2000,740:169-177
[64]Christian R,Anita F.Cationic β-cyclodextrin:a new versatile chiral additive for separation of drug enantiomers by high-performance liquid chromatography.J.Chromatogr.,1995,704:67-74
[65]Jansz D,Danuta S.β-cyclodextrin as a chiral component of the mobile phase for separation of mandelic acid into enantiomers in reversed-phase systems of high-performance liquid chromatography.J.Chromatogr.,1982,237:303-306
[66]Mikael H,Roland I,Curt P.Cellobiohydrolase I as a chiral additive in capillary Electrophoresis and liquid chromatography.J.Chromatogr.A.,1998,807:297-305
[67]李桦,胡先明,谢颖峰.高效液相色谱手性流动相添加剂分离肾上腺素类对映体.色谱,1998,16(5):424-426
[68]谢剑炜,杨造萍,阮金秀.手性药物对映体的环糊精手性流动相、手性固定相HPLC法拆分.药学学报,1998,33(2):143-147
[69]程增江,杨造萍.HPLC法在分离和测定药物对映体中的应用.国外医学-药学分册,1992,19(1):32-36
[70]安登魁.现代药物分析选论.北京:中国医药出版社,2001:264-301
[71]洪建文,胡昌勤,盛龙生.喹诺酮类药物色谱手性分析的进展.药物分析杂志,2003,23(2):155-159
[72]Zeng S,Zong J,Pan L,et al.Separation of ofloxacin enantiomers by using preparative chiral chromatography.Chin J Chromatogr,1996,14(4):280-285
[73]Longh WJ(ed).Chiral Liquid Chromatography.New York:Blackie,1989:83
[74]汪家鼎,溶剂萃取手册.北京:化学工业出版社,2000:996-999
[75]Oshima T,Inoue K,Furusaki S,et al.Liquid membrane transport of amino acids by a calix[6]arene carboxylic acid derivative.J.Membr.Sci.,2003,217:87-97
[76]胡卫国,焦飞鹏,黄可龙,等.厚体液膜动力学拆分普萘洛尔外消旋体.高等学校化学学报,2008,29(2):328-331
[77]卢小宁,陈义.基于二元手性选择剂协同作用的毛细管电泳拆分氨基酸对映体研究.高等学校化学学报,2002,5:822-824
[78]Bin Tan,GuangSheng Luo,Xuan Qi,et al.Enantioselective extraction of D,L-tryptophan by a new chiral selector:Complex formation with di(2-ethy-lhexyl)phosphoric acid and O,O'-dibenzoyl-(2R,3R)-tartaric acid.Sep.Purif. Technol.,2006,49:186-191
[79]Bin Tan,GuangSheng Luo,JiaDing Wang.Enantioseparation of amino acids by co-extractants with di(2-ethylhexyl)phosphoric acid and tartaric acid derivatives.Tetrahedron:Asymmetry,2006,17:883-891.
[80]焦飞鹏,黄可龙,彭霞辉,等.手性配体交换乳状液膜选择性萃取扁桃酸对映体.膜科学与技术,2006,26(2):76-79
[81]崔玉,尹少宏,孙国新,等.正辛基-L-羟基脯氨酸萃取苯丙氨酸的机理及性能.高等学校化学学报,2008,29(5):882-886
[82]Subramanian G.Chiral Separation Techniques,German:Wiley-VCH Verlag GmbH,2001
[83]Tang KW,Chen YY,Huang KL,et al.Enantioselective resolution of chiral aromatic acids by biphasic recognition chiral extraction.Tetrahedron:Asymmetry,2007,18,2399-2408
[84]Ferreira Q,Coelhoso IM,Ramalhete N.et al.Resolution of racemic propranolol in liquid membranes containing TA-β-cyclodextrin.Sep.Sci.Technol.,2006,41(16):3553-3568
[85]Keurentjes LJ,Nabuurs WM,Vegter EA.Liquid membrane technology for the separation of racemic mixtures.J.Membr.Sci.,1996,113:351-360
[86]梁擘,吴兆亮,胡滨,等.泡沫浮选萃取法分离精氨酸.现代化工,2008,28(7):43-46
[87]Daniel WA,Eve YZ,Chen shushi,et al.Foam flotation enrichment of enantiomers.Anal.Chem.,1994,66:4278-4282
[88]陈敏,蔡同一,倪元颖.水溶性2-羟丙基-β-环糊精的合成.食品工业科技,1998,6:8-9
[89]姚玉英等.化工原理(下册).天津大学:天津大学出版社,2002
[90]康杰分,李清岭,寿崇琦,等.环糊精及其衍生物在毛细管电泳手性拆分中的应用.化学分析计量,2006,15:106-108
[91]张国丽,唐课文,黄可龙,易健民.紫外光谱研究β-环糊精衍生物与A-环己基扁桃酸的包结作用.光谱实验室,2007,24(2):81-84
[92]Blaschke G,Kaft HP,Fickentscher K,et al.Chromatographic racemic separation of thalidomide and teratogenic activtity of its enantiomers.Arxneim-Farsch.1979,29(10):1640-1648
[93]崔节虎,李德亮,郑宾国.D2EHPA络合萃取邻氨基苯酚的研究.环境学报,2007,26(3):362-365
[2]刘凤艳,庞小琳,郑轶群,甘秀石.手性物质及其拆分方法.辽宁化工,2007,36(11):784-786
[3]余兰,江波.手性技术在药物中的应用.遵义医学院学报,2004,27(2):188-192
[4]朱长生.普萘洛尔的合成与拆分研究.湖南工业职业技术学院报,2003,3(3):18-19
[5]Guxman A,Yuste F,Toscano RA,et al.Absolute configuration of(-)-5-benzoyl -1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid,the active enantiomer of ketorolac.J.Med.Chem.,1986,(29):589-594
[6]Mitscher LA,Sharma PN,Chu-Daniel.DNA gyrase inhibitors 2.Asymmetric synthesis and biological activtity of the enantiomers of 9-fluoro-3- methyl-10-(4-methyl-1-piperacinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzox azine-6-carbox Ylic acid(ofloxacin).J.Med.Chem.,1987,30(12):2283-2291
[7]Plenge P,Mellerup ET,Honore T,et al.The activity of 25 paroxetine/femixetine structure variants in various reactions,assumed to be important for the effect of antidepressants.J.Pharm.Pharmcal.,1987,39(11):877-882
[8]杨健,向钰.镇咳药左旋羟苯哌嗪的合成.药物研究,2000,9(3):25-25
[9]Blaschke G,Kaft HP,Fickentscher K,et al.Chromatographic racemic separation of thalidomide and teratogenic activtity of its enantiomers.Arxneim-Farsch.1979,29(10):1640-1649
[10]Goodwin SD,Gallis HA,Chow AT.Phanmacology and safety of levofloxacin in patients with human immunodeficiency virus infection.Antimicrob Aents Chemother,1994,(38):799-805
[11]Tobert JA,Cirillo VJ,Hitsenberger G,et al.Enhancement of uricosuric properties of indacrinone by manipulation of the eantiomer ratio.Clin.Pharmacal.Ther.,1981,29(3):344-353
[12]Gold EH,Chang W,Coben M,et al.Synthesis and comparison of some cardiovascular properties of the stereoisomers of labetalol.Med.Chem.,1982,(25):1363-1369
[13]Michael J.Single enantiomer drugs:new strategies and directions.Chemistry& Industry,1996,5(20):374-378
[14]Miriam L.Membranes make chiral separations simpler.Manufacturing Chemist,1995,10:25-32
[15]Gimenez F,Pennie RA,Crevoisier C.Stereoselective pharmacokinetics of mefl-oquine in healthy caucasinans after multiple does.J.Pharm.Sci.,1994,83(6):824-827
[16]Sylvie L,DidierV,Alain VW,et al.SMB enantioseparation:process development,modeling,and operating conditions.AIChE J.,2000,46(2):247-256
[17]James ER.Chiral separations.AIChE J.,2001,47(1):2-5
[18]Botsaris DG,Qian RY,Barrett A.New insights into nucleation through chiral crystallization.AIChE J.,1999,45(1):201-203
[19]肖畴阡,宋光泉.有机化学.中山大学出版社,1996:196
[20]邓金根,迟永祥,朱懂,蒋耀忠.化学拆分的新方法研究.合成化学,1999,7(4):340-345
[21]Schmid A,Dordick JS.,Kiener A,Wubbolts M,Witholt B,Industrial Biocatalysis today and tomorrow.Nature,2001,409(6817):258-268
[22]周志强,张红雁,于兆文,等.高效液相色谱法对外消旋药物的拆分.分析测试技术与仪器,1998,4(1):1-7
[23]曾苏,章立,沈向忠,等.光学异构体的气相色谱拆分法.色谱,1994,12(4):59-262
[24]谢锐,褚良银,曲剑波.手性拆分膜的研究与应用新进展.现代化工,2004,24(4):15-18
[25]Gabelman A,Hwang S-T.Hollow fiber membrane contactors.J.Membr.Sci.,1999,159:61-106
[26]Vankelecom IFJ,Grobet P,Yoshikawa M,et al.Membranes based on poly(7-methyl-1-glutamate):synthesis,characterization and use in chiral separations.J.Membr.Sci.,2001,186:153-163
[27]Maruyama A,Adachi N,Takasuki T,et al.Enantioselective permeation of α-amino acid isomers through poly(amino acid)-derived membranes.Macromolecule,1990,23:2748-2752
[28]Yashima E,Noguchi J,Okamoto Y.Continuous and preparative enantio separation of Oxprenolol with cellulose Tris(3,5-dimethylphenyl-carbamate) -coated Belt.Tetra.Asymm.,1995,6(8):1889-1890
[29]Yashima E,Noguchi J,Okamoto Y.Enantiomer Enrichment of Oxprenolol through cellulose tris(3,5-dimethylphenylcarbamate)membrane.J.Appl.Polym.Sci.,1994,54:1087-1091
[30]Teruyuki M,Masaharu S,Sersuji T.Optical resolution of amino acid by enantioselective ultrafiltration memberane.J.Chem.Eng.Jpn.,1992,25(1):33-38
[31]Thoelen C,Debryn M,Theunissen E.Membrane based on poly(γ-methyl-L-glutamate):synthesis,characterization and use in chiral separations.J.Membr.Sci.,2001,186:153-163
[32]张瑞华等.液膜分离技术.南昌:江西人民出版社,1984.14-15
[33]Cohoso IM,Cadoso MM,Viegas RMC,et al.Transport mechanisms and modeling in liquid membrane contactors.Sep.Purif.Technol.,2000,19(3):183-197
[34]谭斌,骆广生,元暄.液膜及液膜萃取拆分手性物质的研究进展.现代化工,2005,25,13-15
[35]唐课文,周春山,蒋新宇.支持液膜双有机相萃取分离氧氟沙星外消旋体.中国科学,2002,32(6):491-496
[36]戴荣继,苏彩莲,佟斌.膜拆分法分离制备手性药物.膜科学与技术,2006,26(3):84-88
[37]Pickering PJ,Chaudhuri JB.Enantioselective extraction of(D)-phenylalanine from racemic(D/L)-phenylalanine using chiral emulsion liquid membranes.J.Membr.Sci.,1997,127(2):115-130
[38]Oshima T,Inoue K,Furusaki S,Goto M.Liquid membrane transport of amino acids by a calyx[6]arene carboxylic acid derivative.J.Membr.Sci.,2003,217:87-97
[39]黄可龙,胡卫国,焦飞鹏,苏静.厚体液膜拆分克伦特罗外消旋体及其动力学研究.分析化学研究报告,2007,35(4):479-483
[40]Krieg Henning M,Lotter Jeanette,Keizer Klaas,et al.Enrichment of chlorthalidone enantiomers by an aqueous bulk liquid membrane containing β-cyclodextrin.J.Membr.Sci.,2000,167(1):33-38
[41]刘茉娥,陈欢林.新型分离技术基础.杭州:浙江大学出版社,1993,46
[42]汪德进.泡沫分离技术及其模型的研究进展.安庆师范学院学报(自然科学版),2002,3(13):44-46
[43]董红星,李占双,李凯峰,等.泡沫分离法除去污水中十二烷基苯磺酸纳的研究.应用科技,2003,30(3):48-49
[44]Walling CW,Ruff EE,Thorntn JL.Studies on the Separation of Cadrnium from by Foam Separation.Phys Chem,1957,(61):486-493
[45]Rubin A J,Johnson JD,Lamb JC.Comparison of Variables in Ion and Precipitate Flotation.Eng.Chem.Process Des.Dev.,1996,(5):368-372
[46]Yun-Hwei Shen.Colloidal titanium dioxide sepasration from water by foam flotation.Sep.Sci.tech.,1998,33(16):2623-2635
[47]Chien-shu Luo,Shang-da Huang.Removal of Copper from aqueous ammine Copper(Ⅱ) Solution by foam flotation.Sep.Sci.tech.,1993,28(7):1395-1418
[48]Koutlemani MM,Mavros P,Zouboulis AI.Recovery of Co~(2+) Ions from Aqueous Solutions by Forth Flotation.Sep.Sci.tech.,1994,29(7):867-888
[49]Moussavi Mobsen.Separation of cyanide ions by foam fractionation.Sep.Sci.tech.,1992,27(6):783-792
[50]Wingrattansopon Pukpong,Seamenom John and Charedj sumecth et al.Biosrptive Flotation in Metal Ions Recovery.Sep.Sci.tech.,1987,22(11):1523-1540
[51]严希康,潇涣华.用基于表面活性剂的分离方法提取庆大霉素Ⅰ:泡沫分离法.中国抗生素杂志,1996,21(4):256-259
[52]陈树晖,褚家瑛,江体乾.泡沫分离技术的实验研究--回收废液中的金.化工学报,1991,34(6):770-774
[53]刘志红,刘铮,丁富新.用饱沫分离法浓缩和分离蛋白质Ⅰ.清华大学学报,1997,37(12):50-54
[54]管志远,丁爱民,沈宏,等.环流气浮分离技术在含Ni(Ⅱ)废水处理中的试验.高校化学工程学报,1998,12(3):293-297
[55]王绢,褚家瑛.泡沫塔吸附分离BF~(4-).化工学报,1994,45(3):380-384
[56]周长春,刘炯天,周志坚.泡沫浮选在生化分离技术中的应用.选煤技术,2002,6:17-21
[57]J.赖亚.泡沫浮选表面化学.北京:冶金工业出版社,1987:88-128
[58]陈欢林.新型分离技术.北京:化学工业出版社,2005:295-310
[59]陈敏恒,丛德滋,方图南.化工原理.北京:化学工业出版社,1986:67-75
[60]Armstrong DW,Schneiderheinze JM,Hwang YS.Bubble fractionation of enantiomers from solution using molecularly imprinted polymers as collectors.Anal.Chem.,1998,70:3717-3719
[61]刘良.扁桃腈和扁桃酸的技术进展.精细化工化纤信息通讯,2002,1:6-6
[62]Arai T,Koike H,K(?)ji H,(?)izumi H.Separation of pyridone carboxylic acid Enantiomers by high-performance liquid chromatography using copper(Ⅱ)-L- amino acid as the eluent.J.Chromatogr.,1988,448:439-444
[63]Rosa HH,Pilar CF.Chromatographic separation of chlorthalidone Enantiomers using β-cyclodextrins as chiral additives.J.Chromatogr.B,2000,740:169-177
[64]Christian R,Anita F.Cationic β-cyclodextrin:a new versatile chiral additive for separation of drug enantiomers by high-performance liquid chromatography.J.Chromatogr.,1995,704:67-74
[65]Jansz D,Danuta S.β-cyclodextrin as a chiral component of the mobile phase for separation of mandelic acid into enantiomers in reversed-phase systems of high-performance liquid chromatography.J.Chromatogr.,1982,237:303-306
[66]Mikael H,Roland I,Curt P.Cellobiohydrolase I as a chiral additive in capillary Electrophoresis and liquid chromatography.J.Chromatogr.A.,1998,807:297-305
[67]李桦,胡先明,谢颖峰.高效液相色谱手性流动相添加剂分离肾上腺素类对映体.色谱,1998,16(5):424-426
[68]谢剑炜,杨造萍,阮金秀.手性药物对映体的环糊精手性流动相、手性固定相HPLC法拆分.药学学报,1998,33(2):143-147
[69]程增江,杨造萍.HPLC法在分离和测定药物对映体中的应用.国外医学-药学分册,1992,19(1):32-36
[70]安登魁.现代药物分析选论.北京:中国医药出版社,2001:264-301
[71]洪建文,胡昌勤,盛龙生.喹诺酮类药物色谱手性分析的进展.药物分析杂志,2003,23(2):155-159
[72]Zeng S,Zong J,Pan L,et al.Separation of ofloxacin enantiomers by using preparative chiral chromatography.Chin J Chromatogr,1996,14(4):280-285
[73]Longh WJ(ed).Chiral Liquid Chromatography.New York:Blackie,1989:83
[74]汪家鼎,溶剂萃取手册.北京:化学工业出版社,2000:996-999
[75]Oshima T,Inoue K,Furusaki S,et al.Liquid membrane transport of amino acids by a calix[6]arene carboxylic acid derivative.J.Membr.Sci.,2003,217:87-97
[76]胡卫国,焦飞鹏,黄可龙,等.厚体液膜动力学拆分普萘洛尔外消旋体.高等学校化学学报,2008,29(2):328-331
[77]卢小宁,陈义.基于二元手性选择剂协同作用的毛细管电泳拆分氨基酸对映体研究.高等学校化学学报,2002,5:822-824
[78]Bin Tan,GuangSheng Luo,Xuan Qi,et al.Enantioselective extraction of D,L-tryptophan by a new chiral selector:Complex formation with di(2-ethy-lhexyl)phosphoric acid and O,O'-dibenzoyl-(2R,3R)-tartaric acid.Sep.Purif. Technol.,2006,49:186-191
[79]Bin Tan,GuangSheng Luo,JiaDing Wang.Enantioseparation of amino acids by co-extractants with di(2-ethylhexyl)phosphoric acid and tartaric acid derivatives.Tetrahedron:Asymmetry,2006,17:883-891.
[80]焦飞鹏,黄可龙,彭霞辉,等.手性配体交换乳状液膜选择性萃取扁桃酸对映体.膜科学与技术,2006,26(2):76-79
[81]崔玉,尹少宏,孙国新,等.正辛基-L-羟基脯氨酸萃取苯丙氨酸的机理及性能.高等学校化学学报,2008,29(5):882-886
[82]Subramanian G.Chiral Separation Techniques,German:Wiley-VCH Verlag GmbH,2001
[83]Tang KW,Chen YY,Huang KL,et al.Enantioselective resolution of chiral aromatic acids by biphasic recognition chiral extraction.Tetrahedron:Asymmetry,2007,18,2399-2408
[84]Ferreira Q,Coelhoso IM,Ramalhete N.et al.Resolution of racemic propranolol in liquid membranes containing TA-β-cyclodextrin.Sep.Sci.Technol.,2006,41(16):3553-3568
[85]Keurentjes LJ,Nabuurs WM,Vegter EA.Liquid membrane technology for the separation of racemic mixtures.J.Membr.Sci.,1996,113:351-360
[86]梁擘,吴兆亮,胡滨,等.泡沫浮选萃取法分离精氨酸.现代化工,2008,28(7):43-46
[87]Daniel WA,Eve YZ,Chen shushi,et al.Foam flotation enrichment of enantiomers.Anal.Chem.,1994,66:4278-4282
[88]陈敏,蔡同一,倪元颖.水溶性2-羟丙基-β-环糊精的合成.食品工业科技,1998,6:8-9
[89]姚玉英等.化工原理(下册).天津大学:天津大学出版社,2002
[90]康杰分,李清岭,寿崇琦,等.环糊精及其衍生物在毛细管电泳手性拆分中的应用.化学分析计量,2006,15:106-108
[91]张国丽,唐课文,黄可龙,易健民.紫外光谱研究β-环糊精衍生物与A-环己基扁桃酸的包结作用.光谱实验室,2007,24(2):81-84
[92]Blaschke G,Kaft HP,Fickentscher K,et al.Chromatographic racemic separation of thalidomide and teratogenic activtity of its enantiomers.Arxneim-Farsch.1979,29(10):1640-1648
[93]崔节虎,李德亮,郑宾国.D2EHPA络合萃取邻氨基苯酚的研究.环境学报,2007,26(3):362-365