3-（1-萘氧基）-1，2-环氧丙烷水解动力学拆分及其应用的研究
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摘要
手性末端环氧化合物是有机合成的重要砌块,在生物活性化合物制备中的地位与需求日益突出。尽管目前以不对称合成的方法来获得高光学纯度的末端环氧化合物的研究已取得了巨大的进展,但从成本、效率、可控性及环境友好等角度出发,Jacobson研究小组创建的水解动力学拆分的方法依然具有一定的优势。
3-(1-萘氧基)-1,2-环氧丙烷的水解动力学拆分的产物之一是合成抗高血压和心血管疾病的重要药物(S)-萘哌地尔的关键中间体。本文以手性Salen Co(Ⅲ)络合物为催化剂,探讨了该末端环氧化合物水解动力学拆分的各种影响因素及拆分产物在(S)-萘哌地尔制备中的应用。主要研究内容和结果如下：
(1)以标准化的水解动力学拆分反应处理3-(1-萘氧基)-1,2-环氧丙烷,在建立反应转化率及产物光学纯度定量分析方法的基础上,进而详细研究了催化剂种类与用量、反应时间与温度、水的用量、溶剂种类等对上述两因素的影响,确定了该末端环氧化合物水解动力学拆分的最佳条件,即：四氢呋喃做溶剂,水的用量为0.55eq,以手性1,2-环己二胺为配体的催化剂用量为0.75mo1%,室温下反应40h,以49%的收率与100%的ee值,得到(S)-3-(1-萘氧基)-1,2-环氧丙烷。
(2)参考文献的合成路线,将拆分的产物(S)-3-(1-萘氧基)-1,2-环氧丙烷用于(S)-萘哌地尔类似物的制备。在制备中采用超声波促进的方法以实现(S)-3-(1-萘氧基)-1,2-环氧丙烷与N-取代哌嗪的反应,使原来在常规加热条件下需要高温回流反应30小时左右的反应在室温下超声辐射5小时即可完成,大大提高了反应的效率。此法证明对含有脂肪、芳香、杂芳香及杂环取代的哌嗪均有效,都能获得良好的反应产率。我们对制备的(S)-萘哌地尔类似物进行了包括熔点、比旋光值、红外、质谱、氢核磁共振以及碳核磁共振等详细的表征,为快速高效获得(S)-萘哌地尔及其类似物提供了新的制备途径。
Chiral terminal epoxides are important building blocks in organic synthesis, the status and needs of which is increasingly prominent in the preparation of bioactive compounds. Although the asymmetric synthesis method to obtain high optical purity of terminal epoxides has made tremendous progress, from the perspective of cost, efficiency and environment-friendly, the method of hydrolytic kinetic resolution created by Jacobson's group still has certain advantages.
One of the product of the hydrolytic kinetic resolution for 3-(1-naphthyloxy)-1,2-epoxypropane is the key intermediate for (S)-naftopidil, which is the important drug for treatment of arterial hypertension and cardiovascular disease. We explored the various factors of hydrolytic kinetic resolution of terminal epoxides by chiral Salen(III) complex and applied the split product for the preparation of (S)-naftopidil. The major research and result was as followings:
(1) 3-(1-naphthyloxy)-1,2-epoxypropane was treated by the standardized reaction of hydrolytic kinetic resolution. Based on the quantitative analysis method of the conversion rate and the optical purity, further detailed study of the type and amount of catalyst, reaction time, temperature, the amount of water, solvents how to affect these aforesaid factors, we obtained the optimized reaction condition:the solvent was tetrahydrofuran, the water was 0.55 euqivalent, the amount of catalyst was 0.75mol% that was prepared by the chiral ligand 1,2-diaminocyclohexane, the temperature was at room temperature, reaction time was 40 hours. Under the reaction condition, we acquired 49% yield and 100% ee for (S)-3-(1-naphthyloxy)-1,2-epoxypropane.
(2) Based on some synthetic route reported, we applied the split product (S)-3-(1-naphthyloxy)-1,2-epoxypropane to synthesize the (S)-naftopidil analogues. We adopted ultrasound-promoted method to achieve the reaction between 3-(1-naphthyloxy)-1,2-epoxypropane and N-substituted piperazine derivatives. While the reaction under conventional condition required high-temperature refluxing for 30 hours, under ultrasound-assisted condition it finished at room temperature for 5 hours, significantly improving the efficiency. The method proved to contain aliphatic, aromatic, heteroaromatic and heterocyclic substituted piperazine derivatives were effective and could obtain good yield. The prepared (S)-naftopidil analogues were characterized by melting point, specific rotation, IR,1H NMR,13C NMR and MS in detail. It fast and efficiently provided a new way for acquiring (S)-naftopidil analogues.
3-(1-萘氧基)-1,2-环氧丙烷的水解动力学拆分的产物之一是合成抗高血压和心血管疾病的重要药物(S)-萘哌地尔的关键中间体。本文以手性Salen Co(Ⅲ)络合物为催化剂,探讨了该末端环氧化合物水解动力学拆分的各种影响因素及拆分产物在(S)-萘哌地尔制备中的应用。主要研究内容和结果如下：
(1)以标准化的水解动力学拆分反应处理3-(1-萘氧基)-1,2-环氧丙烷,在建立反应转化率及产物光学纯度定量分析方法的基础上,进而详细研究了催化剂种类与用量、反应时间与温度、水的用量、溶剂种类等对上述两因素的影响,确定了该末端环氧化合物水解动力学拆分的最佳条件,即：四氢呋喃做溶剂,水的用量为0.55eq,以手性1,2-环己二胺为配体的催化剂用量为0.75mo1%,室温下反应40h,以49%的收率与100%的ee值,得到(S)-3-(1-萘氧基)-1,2-环氧丙烷。
(2)参考文献的合成路线,将拆分的产物(S)-3-(1-萘氧基)-1,2-环氧丙烷用于(S)-萘哌地尔类似物的制备。在制备中采用超声波促进的方法以实现(S)-3-(1-萘氧基)-1,2-环氧丙烷与N-取代哌嗪的反应,使原来在常规加热条件下需要高温回流反应30小时左右的反应在室温下超声辐射5小时即可完成,大大提高了反应的效率。此法证明对含有脂肪、芳香、杂芳香及杂环取代的哌嗪均有效,都能获得良好的反应产率。我们对制备的(S)-萘哌地尔类似物进行了包括熔点、比旋光值、红外、质谱、氢核磁共振以及碳核磁共振等详细的表征,为快速高效获得(S)-萘哌地尔及其类似物提供了新的制备途径。
Chiral terminal epoxides are important building blocks in organic synthesis, the status and needs of which is increasingly prominent in the preparation of bioactive compounds. Although the asymmetric synthesis method to obtain high optical purity of terminal epoxides has made tremendous progress, from the perspective of cost, efficiency and environment-friendly, the method of hydrolytic kinetic resolution created by Jacobson's group still has certain advantages.
One of the product of the hydrolytic kinetic resolution for 3-(1-naphthyloxy)-1,2-epoxypropane is the key intermediate for (S)-naftopidil, which is the important drug for treatment of arterial hypertension and cardiovascular disease. We explored the various factors of hydrolytic kinetic resolution of terminal epoxides by chiral Salen(III) complex and applied the split product for the preparation of (S)-naftopidil. The major research and result was as followings:
(1) 3-(1-naphthyloxy)-1,2-epoxypropane was treated by the standardized reaction of hydrolytic kinetic resolution. Based on the quantitative analysis method of the conversion rate and the optical purity, further detailed study of the type and amount of catalyst, reaction time, temperature, the amount of water, solvents how to affect these aforesaid factors, we obtained the optimized reaction condition:the solvent was tetrahydrofuran, the water was 0.55 euqivalent, the amount of catalyst was 0.75mol% that was prepared by the chiral ligand 1,2-diaminocyclohexane, the temperature was at room temperature, reaction time was 40 hours. Under the reaction condition, we acquired 49% yield and 100% ee for (S)-3-(1-naphthyloxy)-1,2-epoxypropane.
(2) Based on some synthetic route reported, we applied the split product (S)-3-(1-naphthyloxy)-1,2-epoxypropane to synthesize the (S)-naftopidil analogues. We adopted ultrasound-promoted method to achieve the reaction between 3-(1-naphthyloxy)-1,2-epoxypropane and N-substituted piperazine derivatives. While the reaction under conventional condition required high-temperature refluxing for 30 hours, under ultrasound-assisted condition it finished at room temperature for 5 hours, significantly improving the efficiency. The method proved to contain aliphatic, aromatic, heteroaromatic and heterocyclic substituted piperazine derivatives were effective and could obtain good yield. The prepared (S)-naftopidil analogues were characterized by melting point, specific rotation, IR,1H NMR,13C NMR and MS in detail. It fast and efficiently provided a new way for acquiring (S)-naftopidil analogues.
引文
[1]手性合成—不对称反应及其应用林国强等著 北京：科学出版社,2000.3
[2]Harolde.; Zaugg. A Mechanical Resolution of Methadone Base. J. Am. Chem. Soc..1955,77,2910-2912
[3]Mereyala, H. B.; Pola, P. Resolution of 1-aryl ethyl amines with 5-(1,2-O-isopropy lidene-3,6-anhydro-a-D-glucofuranosyl) hydrogen phthalate. Tetrahedron:Asym-metry.2003,14,2683-2685.
[4]张成刚,罗焕,秦圣英.(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分 化学研究与应用,2006,18,165-168.
[5]Fujima, Y.; Ikunaka, M.; Inoue, T.; Matsumoto, J. Synthesis of (S)-3-(N-Methy lamino)-1-(2-thienyl)propan-1-ol:Revisiting Eli Lilly's Resolution-Racemization-Recycle Synthesis of Duloxetine for Its Robust Processes. Org. Process Res. Dev.2006,10,905-913
[6]冯小明,曾德超,蒋耀忠.一种新的手性拆分方法一包结拆分.有扔化学，2000,20,131-137
[7]Toda, F.; Tanaka, K. A New Optical Resolution Method of Tertiary Acetylenic Alchohol Utilizing Complexation With Brucine. Tetrahedron Lett,1981,22, 4669-4672.
[8]Cai, D.; Hughes, D. L,; Verhoeven, T. R.; Reider, P. J. Simple and Efficient Resolution of 1,1'-Bi-2-naphthol Tetrahedron Lett,1995,36,7991-7994.
[9]Takeuchi, M.; Yoda, S.; Imada, T.; Shinkai, S.; Chiral Sugar Recognition by a Dibronic-Acid-Appended Binaphthyl Derivative through Rigidification Effect. Tetrahedron.1997,53,8335-8348
[10]Naasz, R.; Arnold, L. A.; Minnaard, A. J.; Feringa, B. L. Highly Enantioselect-ive Copper-Phosphoramidite Catalyzed Kinetic Resolution of Chiral 2-Cyclohex enones. Angew. Chem. Int. Ed.2001,40,927-930.
[11]Drago, C.; Caggiano, L.; Jackson, R. F. M. Vanadium-Catalyzed Sulfur Oxidat-ion/Kinetic Resolution in the Synthesis of Enantiomerically Pure Alkyl Aryl Sulfoxides Angew. Chem. Int. Ed.2005,44,7221-7223.
[12]Lorenz, J. C.; Frohn, M.; Zhou, X.; Zhang, J. R.; Tang, Y.; Burke, C.; Shi, Y. Transition State Studies on the Dioxirane-Mediated Asymmetric Epoxidation via Kinetic Resolution and Desymmetrization J. Org. Chem.2005,70,2904-2911.
[13]Spivey, A. C.; Arseniyadis, S.; Fekner, T.; Maddaford, A.; Leese, D. P. Rapid roomtemperature acylative kinetic resolution of sec-alcohols using atropisomeric 4-aminopyridine/triphenylphosphine catalysis Tetrahedron 2006,62,295-301.
[14]Tokunage, M.; Larrow, J. F.; Jacobsen, E. N. Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydro-lysis. Science,1997,277,936-938.
[15]沈凯圣,熊飞,胡娟.手性(Salen) Co催化的末端环氧化合物水解动力学拆分反应在手性药物合成中的应用.有机化学，2003,23,542-545.
[16]Choi, M. Y.; Khaskin, G.; Gries, R.; Gries, G.; Roitber, B. D.; Raworth, D. A.; Kim, D. H.;Bennett, R.G. (2R,7S)-Diacetoxytridecane:Sex Pheromone of the Aphidophagous Gall Midge, Aphidoletes aphidimyza. J. Chem.Ecol.2004,30, 659-670.
[17]Hasegawa, T.; Kawanaka,Y.; Kasamatsu, E.; Nakabayashi, K. A New Process for Synthesis of the Astrocyte Activation Suppressor, ONO-2506. Org. Process Res.Dev.2005,9,774-781.
[18]Stiirrner, R. A New Route to Highly Enantiomerically Enriched (Z)-(1-Methyl-2-butenyl) boronic Esters Angew. Chem. Int. Ed. Engl.1990,29,59-60.
[19]Noyori, R.; Takaya, H. BINAP:An Efficient Chiral Element for Asymmetric Catalysis. Ace. Chem. Res.1990,23,345-350.
[20]Ding, Z.; Yang, J.; Wang, T.; Shen, Z.; Zhang, Y. Dynamic kinetic resolution of β-keto sulfones via asymmetric transfer hydrogenation. Chem. Commun.2009, 571-573.
[21]段钢.陈家铺.光学活性物质的工业生产方法.化工进展,1995,2,32-36.
[22]Bevinakatti, H. S.; Banerji. A. A. Practical Chemoenzymatic Synthesis of Both Enantiomers of Propranolol. J. Org. Chem.1991,56,5372-5375.
[23]Javier, G.; Gotor, V.; Rebolledo, F. CAL-B-catalyzed resolution of some pharma- cologically interesting substituted isopropylamines
[24]Chen, P. R.; Geng, X. H.; Xu, Q. Enzymatic kinetic resolution of racemic cyano-hydrins via enantioselective acylation. Tetrahedron 2010,66,624-630.
[25]曾苏,章立,沈向忠.光学异构体的气相色谱拆分法.色谱,1994,12,259-262.
[26]匡唐永,张家美,邹安庆.手性毛细管色谱法测定人尿中美芬妥英光学异构体含量的方法学研究 药学学报,1993,28,307-311.
[27]章立,姚彤炜,曾苏.柱前手性衍生化-毛细管气相色谱测定大鼠肝微粒体中安非他明对映体.药物分析杂志,1998,18,291-295.
[28]张月琴,傅若农,张汉邦,凌云.环糊精接枝聚硅氧烷气相色谱固定相的手性拆分性能 分析测试学报,2002,21,31-33.
[29]Gotti, R.; Pomponio, R.; Andrisano, V.; Cavrini, V. Analytical study of penicill-amine in pharmaceuticals by capillary zone electrophoresis. J. Chromatogr. A, 1999,844,361-369.
[30]侯经国,何天稀,刘慧玲,邓华陵,毛学峰,杜新贞,高锦章.红霉素作为毛细管区带电泳手性选择剂拆分两种联苯双酯类药物.色谱.2003,21,72-75.
[31]肖美添,黄雅燕,郭养浩.扁桃酸甲酯对映体的毛细管电泳手性拆分,分析测试学报,2003,22,47-49.
[32]Berssolle, F.; Andrna, M.; Phar, T. N. Cyelodexrtinsnad Enantlomeric Separatio-ns of Durgs by Liquid Chromoatgrpahy and Capillary Electrophoresis:Basic Principles and New developments. J. Chromatogr. B,1996,687,303-336.
[33]Vanessal, L.; Herring, Y. Direct HPLC Determination in Urine of the Enantiomer of Propranolol and its Major Basic Metabolite 4-Hydroxypropranolol J.Chromat-og B, Biomed. Appl.1993,612,215-221.
[34]周志强,王鹏,江树人,王敏.涂敷型淀粉类液相色谱手性固定相对丙烯菊醇对映体的拆分.色谱,2003,21,44-45.
[35]丁国生,唐安娜,王俊德.替考拉宁键合手性固定相高效液相色谱法直接拆分泮托拉唑钠对映体.色谱，2006,24,46-48.
[36]Petersson, P.;Markides, K. E. Chiral Separation Performed by Supercritical Fluid Chromatography. J Chromatogr A,1994,666,381-394.
[37]马建茵.手性药物的色谱分离方法 中国医药工业杂志，2002,33,199-202.
[38]Steuer, W.; Schindler, M.; Schill, G.; Erni, F. Supercritical fluid chromatography with ion-pairing modifiers Separation of enantiomeric 1,2-aminoalcohols as diastereomeric ion pairs J. Chromatogr. A,1988,447,287-296.
[39]Wilkins, M. S.; Taylor, D. R.; Smith, R. J. Enatatiomer separations by supercriti-cal fluid chromatography on a chiral stationary phase physically anchored a porous graphical carbon. J. Chromatogr. A.1995,697,587-590.
[40]Liu, Y.; Main, B.; Clifford, R. Super/subcritical Fluid Chromatography Chiral Separations with Macrocychc Glyeopeptide Stationary Phases. J.Chromatogr. A,2002,978,185-204.
[41]朱全红,邓芹英,曾陇梅.手性药物的薄层色谱拆分.药物分析杂志.2002,22，155-158.
[42]郝爱友,童林荟,张复升.β-环糊精为TLC流动相添加剂分离对映体.化学通报,1996,4,16-18.
[43]徐国珍.薄层色谱分离酪胺酸异构体研究.食品研究与开发,1998,19,22-24.
[44]黄慕斌,李洪宽.环糊精流动相添加剂分离色氨酸对映体的薄层色谱法.色谱.1995,13,120-122.
[45]方艳红,王琼,徐金瑞.反相薄层色谱法拆分D,L-苯丙氨酸对映体.理化检验-化学分册.2005,41,241-243.
[46]于金刚,黄可龙,焦飞鹏.p-环糊精固载硅胶薄层色谱法拆分盐酸克伦特罗对映体.色谱,2005,23,431-433.
[47]李俊,蔡水洪,朱中南,赵玲.手性化合物的萃取拆分研究.化学世界，2001,5，233-236.
[48]Tsukube, H.; Shinoda, S., Uenshi, J; Kanatani, T.; Itoh, H.; Shiode, M.; Iwachido ,T.; Yonemitsu, O. Molecular Recognition with Lanthanide(Ⅲ) Tris(β-diketonat-e) Complexes:Extraction, Tranisport, and Chiral Recognition of Unprotected A-mino Acids. Inorg. Chem.1998,57,1585-1591.
[49]Fogassy, E.; Szili, T.; Sawinsky, J. Molecular Chairl Recognition in Supercritical Solvent. Tetrahadron Lett.1994,35,257-260.
[50]Maruyama, A.; Adachi, N.; Takatsuki, T.; Torii, M.; Sanui, K.; Ogata, N. Enantioselective Permeation of α-Amino Acid Isomers through Poly (amino acid)-Derived Membranes. Macromolecules 1990,23,2748-2752.
[51]Pickering, P. J.; Chaudhuri, J. B. Enantioselective extraction of (D)-phenylanine from racemic (D/L)-phenylanine using chairl emulsion liquid membranes. J. Me-mbr.Sci.1997,127,115-130.
[52]Coelhoso, I. M.; Cardoso, M. M.; Viegas, R. M. C.; Crespo J. P. S. G. Transport mechanisms and modelling in liquid membrane contactors Sep. Purif. Technol. 2000,19,183-197.
[53]Nielsen, L. P.; Stevenson, C. P.; Blackmond, D. G.; Jacobsen, E. N. Mechanistic Investigation Leads to aSynthetic Improvement in the Hydrolytic Kinetic Resol ution of Terminal Epoxides. J. Am. Chem. Soc.2004,726,1360-1362.
[54]Pfeiffer, P.; Breith, E.; Lubbe, E.; Tsumaki, T. Tricyclische Orthokondensierte Nebenvalenzringe Justus Lie. Ann.Chem.1933,503,84-130.
[55]Li, L. S.; Wu, Y. K.; Wu, Y. L. Asymmetric hetero-Diels-Alder reaction of l-alkyl-3-silyloxy-1,3-dienes with ethyl glyoxylate catalyzed by a chiral (salen)cobalt(II) complex. Tetrahedron:Asymmetry.1998,9,2211-2277.
[56]Sigman, M. S.; Jacobsen, E. N. Enantioselective Addition of Hydrogen Cyanide to Imines Catalyzed by a Chiral(Salen)Al(III)Complex. J.Am.Chem.Soc.1998, 720,5315-5316.
[57]Finney, N. S.; Pospisil, P. J.; Jacobsen, E. N. On the Viability of Oxametallacycl-ic Intermediates in the (salen)Mn-Catalyzed Asymmetric Epoxidation. Angew. Chem.Int.Ed.Engl.1997,36,1720-1723.
[58]Leighton, J. L.; Jacobsen, E. N. Efficient Synthesis of (R)-4-((Trimethylsilyl)oxy )-2-cyclopentenone by Enantioselective Catalytic Epoxide Ring Opening. J. Org. Chem.1996,61,389-390.
[59]Larrow, J. F.; Jacobsen, E. N. APractical Method for the Large-Scale Preparation of [N,N-Bis(3,5-ditert-butylsalicylidene)-l,2-cyclohexanediaminato(2-)] manga-nese(III) Chloride, a Highly Enantioselective Epoxidation Catalyst. J. Org. Chem. 1994,59,1939-1942.
[60]Schaus, S. E, Larrow, J. F.; Jacobsen, E. N. Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Co(III) Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols. J. Am. Chem. Soc.2002,124,1307-1315.
[61]陈维一,陆军,王小燕,张雅文,沈宗旋.L-半光氨酸衍生物的合成及应用.有机化学.2003,23,1407-1410.
[62]Hansen, T. V.; Skattebφ1, L. A high yielding one-pot method for the preparation of salen ligands. Tetrahedron Lett.2005,46,3829-3830.
[63]Brahmam, P.; Chakraborti, A. K. Zinc(Ⅱ) Perchlorate Hexahydrate Catalyzed Opening of Epoxide Ring by Amines:Applications to Synthesis of (RS)/(R)-Propranolols and (RS)/(R)/(S)-Naftopidils J. Org. Chem.2007,72,3713-3722.
[64]Panchgalle, S. P.;Gore, R. G.; Chavan,S. P.; Kalkote, U. R. Organocatalytic enantioselective synthesis of β-blockers:(S)-propranolol and (S)-naftopidil Tetrahedron:Asymmetry 2009,20,1767-1770.
[65]Bevinakatti, H.S.; Banerji, A.A. Practical Chemoenzymatic Synthesis of Both Enantiomers of Propranolol. J. Org. Chem.1991,56,5372-5375.
[66]Sayyed, I. A, Thakur, V. V.; Nikalje, M. D.; Dewkar, G. K. Asymmetric synthes-is of aryloxypropanolamines via OsO4-catalyzed asymmetric dihydroxylation. Tetrahedron.2005,61,2831-2838.
[67]沈宗旋,李明,邢立东,张雅文.几种外消旋环氧化合物的水解动力学拆分,应用化学,2003,20,144-148.
[68]Sponer, G.; Borbe, H. O.; Frued, P. Naftopidil, a New Adrenoceptor Blocking Agent with Ca2+-Antagonistic Properties:Interation with Adrenoceptor. J. Cardiovasc. Pharmacol.1992,20,1006-1013.
[69]Pollard, C. B.; Fersanandez, J. B. Derivatives of Piperazine. XXXII.1-Aryl-4-(2-hydroxy-3-aryloxypropyl)-piperazines. J. Org. Chem.1958,23,1935-1937.
[70]肖志会.袁牧.黄建设.吴军.苯基哌嗪衍生物的NMR波谱研究.波普学杂志.2004,21,365-368.
[71]付晓钟.汤磊.袁牧.石京山.R,S-1-(取代苯基)-4-[3-(萘-1-氧基)-2-羟基丙 基]哌嗪类化合物的设计、合成及血管舒张活性.药学学报.2004,42,735-740.
[72]Xiao, Z. H.; Yuan, M.; Zhang, S.; Wu, J.; Qi, S. H.; Li, Q. X. Complete assignments of1H and 13C NMR data for ten phenylpiperazine derivatives. Magn. Reson.Che- m.2005,43,869-872.
[73]药物设计学.姜凤超 主编 北京：化学工业出版社.2007年.119-137.
[74]潘建林,陶兰,幸刃,姚碧峰.N-苯基哌嗪的合成.中国现代应用药学杂志，2001,18,372-374.
[75]Nishiyama, M.; Yamamoto, T.; Koie, Y. Synthesis of N-arylpiperazines from aryl halides and piperazine under a palladium tri-tert-butylphosphine catalyst. Tetrah-edron Lett.1998,39,617-620.
[76]Qu, Z. B.; Chen, X. L.; Qu, L. B.; Yuan, J. W.; Li, H. N.; Zhao, Y. F. Synthesis of Novel Piperazine Phosphoramidate Analogues of 2-Arylquinolones. Phospho-rus, Sulfur Silicon Relat. Elem.2010,185,1516-1520.
[77]贾卫国,张鹏,刘振荣,李慧芳,杨奇,王君.超声化学的研究与应用 辽宁大学学报自然版.2002,29，198-202.
[78]Kamal, A.; Adil, S.F.; Arifuddin, M. Ultrasonic activated efficient method for the cleavage of epoxides with aromatic amines. Ultrason. Sonochem.2005,12, 429-431.
[79]刘玉衡.环氧化合物的开环研究.2009年硕士学位论文.河北师范大学.
[80]Kanthale, P.; Ashokkumar, M.; Grieser, F. Sonoluminescence, sonochemistry (H2O2 yield) and bubble dynamics:frequency and power effects, Ultrason. Sonochem.15 2008,15,143-150.
[81]Wang, X.K.; Wei, Y.C.; Wang, J.G; Guo, W.L.; Wang, C. The kinetics and mechanism of ultrasonic degradation of p-nitrophenol in aqueous solution with CCl4 enhancement, Ultrason. Sonochem.2012,19,32-37.
[82]Jiang, Y. Z.; Gong, L. Z.; Feng, X. M. Salen-Ti(OR)4 Complex Catalysed Trimethylsilylcyanation of Aldehydes. Tetrahedron.1997,53,14327-14338.
[2]Harolde.; Zaugg. A Mechanical Resolution of Methadone Base. J. Am. Chem. Soc..1955,77,2910-2912
[3]Mereyala, H. B.; Pola, P. Resolution of 1-aryl ethyl amines with 5-(1,2-O-isopropy lidene-3,6-anhydro-a-D-glucofuranosyl) hydrogen phthalate. Tetrahedron:Asym-metry.2003,14,2683-2685.
[4]张成刚,罗焕,秦圣英.(S)-2-氨基-1,1-二苯基-1-丙醇的合成和外消旋Droxidopa前体的拆分 化学研究与应用,2006,18,165-168.
[5]Fujima, Y.; Ikunaka, M.; Inoue, T.; Matsumoto, J. Synthesis of (S)-3-(N-Methy lamino)-1-(2-thienyl)propan-1-ol:Revisiting Eli Lilly's Resolution-Racemization-Recycle Synthesis of Duloxetine for Its Robust Processes. Org. Process Res. Dev.2006,10,905-913
[6]冯小明,曾德超,蒋耀忠.一种新的手性拆分方法一包结拆分.有扔化学，2000,20,131-137
[7]Toda, F.; Tanaka, K. A New Optical Resolution Method of Tertiary Acetylenic Alchohol Utilizing Complexation With Brucine. Tetrahedron Lett,1981,22, 4669-4672.
[8]Cai, D.; Hughes, D. L,; Verhoeven, T. R.; Reider, P. J. Simple and Efficient Resolution of 1,1'-Bi-2-naphthol Tetrahedron Lett,1995,36,7991-7994.
[9]Takeuchi, M.; Yoda, S.; Imada, T.; Shinkai, S.; Chiral Sugar Recognition by a Dibronic-Acid-Appended Binaphthyl Derivative through Rigidification Effect. Tetrahedron.1997,53,8335-8348
[10]Naasz, R.; Arnold, L. A.; Minnaard, A. J.; Feringa, B. L. Highly Enantioselect-ive Copper-Phosphoramidite Catalyzed Kinetic Resolution of Chiral 2-Cyclohex enones. Angew. Chem. Int. Ed.2001,40,927-930.
[11]Drago, C.; Caggiano, L.; Jackson, R. F. M. Vanadium-Catalyzed Sulfur Oxidat-ion/Kinetic Resolution in the Synthesis of Enantiomerically Pure Alkyl Aryl Sulfoxides Angew. Chem. Int. Ed.2005,44,7221-7223.
[12]Lorenz, J. C.; Frohn, M.; Zhou, X.; Zhang, J. R.; Tang, Y.; Burke, C.; Shi, Y. Transition State Studies on the Dioxirane-Mediated Asymmetric Epoxidation via Kinetic Resolution and Desymmetrization J. Org. Chem.2005,70,2904-2911.
[13]Spivey, A. C.; Arseniyadis, S.; Fekner, T.; Maddaford, A.; Leese, D. P. Rapid roomtemperature acylative kinetic resolution of sec-alcohols using atropisomeric 4-aminopyridine/triphenylphosphine catalysis Tetrahedron 2006,62,295-301.
[14]Tokunage, M.; Larrow, J. F.; Jacobsen, E. N. Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydro-lysis. Science,1997,277,936-938.
[15]沈凯圣,熊飞,胡娟.手性(Salen) Co催化的末端环氧化合物水解动力学拆分反应在手性药物合成中的应用.有机化学，2003,23,542-545.
[16]Choi, M. Y.; Khaskin, G.; Gries, R.; Gries, G.; Roitber, B. D.; Raworth, D. A.; Kim, D. H.;Bennett, R.G. (2R,7S)-Diacetoxytridecane:Sex Pheromone of the Aphidophagous Gall Midge, Aphidoletes aphidimyza. J. Chem.Ecol.2004,30, 659-670.
[17]Hasegawa, T.; Kawanaka,Y.; Kasamatsu, E.; Nakabayashi, K. A New Process for Synthesis of the Astrocyte Activation Suppressor, ONO-2506. Org. Process Res.Dev.2005,9,774-781.
[18]Stiirrner, R. A New Route to Highly Enantiomerically Enriched (Z)-(1-Methyl-2-butenyl) boronic Esters Angew. Chem. Int. Ed. Engl.1990,29,59-60.
[19]Noyori, R.; Takaya, H. BINAP:An Efficient Chiral Element for Asymmetric Catalysis. Ace. Chem. Res.1990,23,345-350.
[20]Ding, Z.; Yang, J.; Wang, T.; Shen, Z.; Zhang, Y. Dynamic kinetic resolution of β-keto sulfones via asymmetric transfer hydrogenation. Chem. Commun.2009, 571-573.
[21]段钢.陈家铺.光学活性物质的工业生产方法.化工进展,1995,2,32-36.
[22]Bevinakatti, H. S.; Banerji. A. A. Practical Chemoenzymatic Synthesis of Both Enantiomers of Propranolol. J. Org. Chem.1991,56,5372-5375.
[23]Javier, G.; Gotor, V.; Rebolledo, F. CAL-B-catalyzed resolution of some pharma- cologically interesting substituted isopropylamines
[24]Chen, P. R.; Geng, X. H.; Xu, Q. Enzymatic kinetic resolution of racemic cyano-hydrins via enantioselective acylation. Tetrahedron 2010,66,624-630.
[25]曾苏,章立,沈向忠.光学异构体的气相色谱拆分法.色谱,1994,12,259-262.
[26]匡唐永,张家美,邹安庆.手性毛细管色谱法测定人尿中美芬妥英光学异构体含量的方法学研究 药学学报,1993,28,307-311.
[27]章立,姚彤炜,曾苏.柱前手性衍生化-毛细管气相色谱测定大鼠肝微粒体中安非他明对映体.药物分析杂志,1998,18,291-295.
[28]张月琴,傅若农,张汉邦,凌云.环糊精接枝聚硅氧烷气相色谱固定相的手性拆分性能 分析测试学报,2002,21,31-33.
[29]Gotti, R.; Pomponio, R.; Andrisano, V.; Cavrini, V. Analytical study of penicill-amine in pharmaceuticals by capillary zone electrophoresis. J. Chromatogr. A, 1999,844,361-369.
[30]侯经国,何天稀,刘慧玲,邓华陵,毛学峰,杜新贞,高锦章.红霉素作为毛细管区带电泳手性选择剂拆分两种联苯双酯类药物.色谱.2003,21,72-75.
[31]肖美添,黄雅燕,郭养浩.扁桃酸甲酯对映体的毛细管电泳手性拆分,分析测试学报,2003,22,47-49.
[32]Berssolle, F.; Andrna, M.; Phar, T. N. Cyelodexrtinsnad Enantlomeric Separatio-ns of Durgs by Liquid Chromoatgrpahy and Capillary Electrophoresis:Basic Principles and New developments. J. Chromatogr. B,1996,687,303-336.
[33]Vanessal, L.; Herring, Y. Direct HPLC Determination in Urine of the Enantiomer of Propranolol and its Major Basic Metabolite 4-Hydroxypropranolol J.Chromat-og B, Biomed. Appl.1993,612,215-221.
[34]周志强,王鹏,江树人,王敏.涂敷型淀粉类液相色谱手性固定相对丙烯菊醇对映体的拆分.色谱,2003,21,44-45.
[35]丁国生,唐安娜,王俊德.替考拉宁键合手性固定相高效液相色谱法直接拆分泮托拉唑钠对映体.色谱，2006,24,46-48.
[36]Petersson, P.;Markides, K. E. Chiral Separation Performed by Supercritical Fluid Chromatography. J Chromatogr A,1994,666,381-394.
[37]马建茵.手性药物的色谱分离方法 中国医药工业杂志，2002,33,199-202.
[38]Steuer, W.; Schindler, M.; Schill, G.; Erni, F. Supercritical fluid chromatography with ion-pairing modifiers Separation of enantiomeric 1,2-aminoalcohols as diastereomeric ion pairs J. Chromatogr. A,1988,447,287-296.
[39]Wilkins, M. S.; Taylor, D. R.; Smith, R. J. Enatatiomer separations by supercriti-cal fluid chromatography on a chiral stationary phase physically anchored a porous graphical carbon. J. Chromatogr. A.1995,697,587-590.
[40]Liu, Y.; Main, B.; Clifford, R. Super/subcritical Fluid Chromatography Chiral Separations with Macrocychc Glyeopeptide Stationary Phases. J.Chromatogr. A,2002,978,185-204.
[41]朱全红,邓芹英,曾陇梅.手性药物的薄层色谱拆分.药物分析杂志.2002,22，155-158.
[42]郝爱友,童林荟,张复升.β-环糊精为TLC流动相添加剂分离对映体.化学通报,1996,4,16-18.
[43]徐国珍.薄层色谱分离酪胺酸异构体研究.食品研究与开发,1998,19,22-24.
[44]黄慕斌,李洪宽.环糊精流动相添加剂分离色氨酸对映体的薄层色谱法.色谱.1995,13,120-122.
[45]方艳红,王琼,徐金瑞.反相薄层色谱法拆分D,L-苯丙氨酸对映体.理化检验-化学分册.2005,41,241-243.
[46]于金刚,黄可龙,焦飞鹏.p-环糊精固载硅胶薄层色谱法拆分盐酸克伦特罗对映体.色谱,2005,23,431-433.
[47]李俊,蔡水洪,朱中南,赵玲.手性化合物的萃取拆分研究.化学世界，2001,5，233-236.
[48]Tsukube, H.; Shinoda, S., Uenshi, J; Kanatani, T.; Itoh, H.; Shiode, M.; Iwachido ,T.; Yonemitsu, O. Molecular Recognition with Lanthanide(Ⅲ) Tris(β-diketonat-e) Complexes:Extraction, Tranisport, and Chiral Recognition of Unprotected A-mino Acids. Inorg. Chem.1998,57,1585-1591.
[49]Fogassy, E.; Szili, T.; Sawinsky, J. Molecular Chairl Recognition in Supercritical Solvent. Tetrahadron Lett.1994,35,257-260.
[50]Maruyama, A.; Adachi, N.; Takatsuki, T.; Torii, M.; Sanui, K.; Ogata, N. Enantioselective Permeation of α-Amino Acid Isomers through Poly (amino acid)-Derived Membranes. Macromolecules 1990,23,2748-2752.
[51]Pickering, P. J.; Chaudhuri, J. B. Enantioselective extraction of (D)-phenylanine from racemic (D/L)-phenylanine using chairl emulsion liquid membranes. J. Me-mbr.Sci.1997,127,115-130.
[52]Coelhoso, I. M.; Cardoso, M. M.; Viegas, R. M. C.; Crespo J. P. S. G. Transport mechanisms and modelling in liquid membrane contactors Sep. Purif. Technol. 2000,19,183-197.
[53]Nielsen, L. P.; Stevenson, C. P.; Blackmond, D. G.; Jacobsen, E. N. Mechanistic Investigation Leads to aSynthetic Improvement in the Hydrolytic Kinetic Resol ution of Terminal Epoxides. J. Am. Chem. Soc.2004,726,1360-1362.
[54]Pfeiffer, P.; Breith, E.; Lubbe, E.; Tsumaki, T. Tricyclische Orthokondensierte Nebenvalenzringe Justus Lie. Ann.Chem.1933,503,84-130.
[55]Li, L. S.; Wu, Y. K.; Wu, Y. L. Asymmetric hetero-Diels-Alder reaction of l-alkyl-3-silyloxy-1,3-dienes with ethyl glyoxylate catalyzed by a chiral (salen)cobalt(II) complex. Tetrahedron:Asymmetry.1998,9,2211-2277.
[56]Sigman, M. S.; Jacobsen, E. N. Enantioselective Addition of Hydrogen Cyanide to Imines Catalyzed by a Chiral(Salen)Al(III)Complex. J.Am.Chem.Soc.1998, 720,5315-5316.
[57]Finney, N. S.; Pospisil, P. J.; Jacobsen, E. N. On the Viability of Oxametallacycl-ic Intermediates in the (salen)Mn-Catalyzed Asymmetric Epoxidation. Angew. Chem.Int.Ed.Engl.1997,36,1720-1723.
[58]Leighton, J. L.; Jacobsen, E. N. Efficient Synthesis of (R)-4-((Trimethylsilyl)oxy )-2-cyclopentenone by Enantioselective Catalytic Epoxide Ring Opening. J. Org. Chem.1996,61,389-390.
[59]Larrow, J. F.; Jacobsen, E. N. APractical Method for the Large-Scale Preparation of [N,N-Bis(3,5-ditert-butylsalicylidene)-l,2-cyclohexanediaminato(2-)] manga-nese(III) Chloride, a Highly Enantioselective Epoxidation Catalyst. J. Org. Chem. 1994,59,1939-1942.
[60]Schaus, S. E, Larrow, J. F.; Jacobsen, E. N. Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Co(III) Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols. J. Am. Chem. Soc.2002,124,1307-1315.
[61]陈维一,陆军,王小燕,张雅文,沈宗旋.L-半光氨酸衍生物的合成及应用.有机化学.2003,23,1407-1410.
[62]Hansen, T. V.; Skattebφ1, L. A high yielding one-pot method for the preparation of salen ligands. Tetrahedron Lett.2005,46,3829-3830.
[63]Brahmam, P.; Chakraborti, A. K. Zinc(Ⅱ) Perchlorate Hexahydrate Catalyzed Opening of Epoxide Ring by Amines:Applications to Synthesis of (RS)/(R)-Propranolols and (RS)/(R)/(S)-Naftopidils J. Org. Chem.2007,72,3713-3722.
[64]Panchgalle, S. P.;Gore, R. G.; Chavan,S. P.; Kalkote, U. R. Organocatalytic enantioselective synthesis of β-blockers:(S)-propranolol and (S)-naftopidil Tetrahedron:Asymmetry 2009,20,1767-1770.
[65]Bevinakatti, H.S.; Banerji, A.A. Practical Chemoenzymatic Synthesis of Both Enantiomers of Propranolol. J. Org. Chem.1991,56,5372-5375.
[66]Sayyed, I. A, Thakur, V. V.; Nikalje, M. D.; Dewkar, G. K. Asymmetric synthes-is of aryloxypropanolamines via OsO4-catalyzed asymmetric dihydroxylation. Tetrahedron.2005,61,2831-2838.
[67]沈宗旋,李明,邢立东,张雅文.几种外消旋环氧化合物的水解动力学拆分,应用化学,2003,20,144-148.
[68]Sponer, G.; Borbe, H. O.; Frued, P. Naftopidil, a New Adrenoceptor Blocking Agent with Ca2+-Antagonistic Properties:Interation with Adrenoceptor. J. Cardiovasc. Pharmacol.1992,20,1006-1013.
[69]Pollard, C. B.; Fersanandez, J. B. Derivatives of Piperazine. XXXII.1-Aryl-4-(2-hydroxy-3-aryloxypropyl)-piperazines. J. Org. Chem.1958,23,1935-1937.
[70]肖志会.袁牧.黄建设.吴军.苯基哌嗪衍生物的NMR波谱研究.波普学杂志.2004,21,365-368.
[71]付晓钟.汤磊.袁牧.石京山.R,S-1-(取代苯基)-4-[3-(萘-1-氧基)-2-羟基丙 基]哌嗪类化合物的设计、合成及血管舒张活性.药学学报.2004,42,735-740.
[72]Xiao, Z. H.; Yuan, M.; Zhang, S.; Wu, J.; Qi, S. H.; Li, Q. X. Complete assignments of1H and 13C NMR data for ten phenylpiperazine derivatives. Magn. Reson.Che- m.2005,43,869-872.
[73]药物设计学.姜凤超 主编 北京：化学工业出版社.2007年.119-137.
[74]潘建林,陶兰,幸刃,姚碧峰.N-苯基哌嗪的合成.中国现代应用药学杂志，2001,18,372-374.
[75]Nishiyama, M.; Yamamoto, T.; Koie, Y. Synthesis of N-arylpiperazines from aryl halides and piperazine under a palladium tri-tert-butylphosphine catalyst. Tetrah-edron Lett.1998,39,617-620.
[76]Qu, Z. B.; Chen, X. L.; Qu, L. B.; Yuan, J. W.; Li, H. N.; Zhao, Y. F. Synthesis of Novel Piperazine Phosphoramidate Analogues of 2-Arylquinolones. Phospho-rus, Sulfur Silicon Relat. Elem.2010,185,1516-1520.
[77]贾卫国,张鹏,刘振荣,李慧芳,杨奇,王君.超声化学的研究与应用 辽宁大学学报自然版.2002,29，198-202.
[78]Kamal, A.; Adil, S.F.; Arifuddin, M. Ultrasonic activated efficient method for the cleavage of epoxides with aromatic amines. Ultrason. Sonochem.2005,12, 429-431.
[79]刘玉衡.环氧化合物的开环研究.2009年硕士学位论文.河北师范大学.
[80]Kanthale, P.; Ashokkumar, M.; Grieser, F. Sonoluminescence, sonochemistry (H2O2 yield) and bubble dynamics:frequency and power effects, Ultrason. Sonochem.15 2008,15,143-150.
[81]Wang, X.K.; Wei, Y.C.; Wang, J.G; Guo, W.L.; Wang, C. The kinetics and mechanism of ultrasonic degradation of p-nitrophenol in aqueous solution with CCl4 enhancement, Ultrason. Sonochem.2012,19,32-37.
[82]Jiang, Y. Z.; Gong, L. Z.; Feng, X. M. Salen-Ti(OR)4 Complex Catalysed Trimethylsilylcyanation of Aldehydes. Tetrahedron.1997,53,14327-14338.