酶促/化学法合成核苷类药物衍生物及其高分子前药
|
摘要
酶促合成方法具有选择性高、反应条件温和等优点,使其在药物及其衍生物的合成中已受到越来越多的关注,具有很好的应用前景。本论文发展了非水介质中酶促选择性合成核苷类药物衍生物的方法。
本文发展了非水介质中含多羟基核苷类药物衍生物的酶促选择性合成方法。研究了2′-脱氧-5-氟尿苷、5-氟尿苷、5-氟胞苷和5′-脱氧-5-氟尿苷四种核苷类药物分别与四种具有不同链长的二酸二乙烯酯(C4,C6,C9,C10)的酶促反应,合成了新型的可聚合药物衍生物。同时考察酶源、反应介质、溶剂含水量、反应时间等各种因素对酶促酯交换反应产率和选择性的影响。反应具有条件温和、选择性高、产率好等特点。
论文研究了2′-脱氧-5-氟尿苷(FUDR)可聚合衍生物的可控制选择性合成。在THF中由固定化CAL-B或在吡啶中由Subtilisin催化的2′-脱氧-5-氟尿苷与二酸二乙烯酯的反应,选择性地发生在FUDR糖环的伯羟基位置;在THF中通过PSL-C催化的FUDR与二酸二乙烯酯的反应,可以得到仲羟基酰化的产物。即通过使用不同的酶实现了在FUDR的不同位置发生反应的选择性控制。5-氟尿苷、5-氟胞苷伯羟基的选择性酰化也成功地实现,选用的酶为CAL-B,溶剂为THF。本文也对5-氟胞苷和5′-脱氧-5-氟尿苷(DFUR)的两仲羟基的选择性进行了详细地研究,但由于两个仲羟基的化学环境太相似,选择性不太理想。
论文对核苷乙烯酯化合物进一步酶促衍生化,合成了一系列核苷类药物—糖类复合物。在吡啶中,用Subtilisin催化核苷乙烯酯衍生物和糖类(葡萄糖、甘露糖、半乳糖)的反应,选择性酰化糖类的特定羟基。其中药物—半乳糖复合物是潜在的靶向性药物。
论文在合成可聚合单体基础上,主要采用AIBN作为引发剂,DMF为反应溶剂合成了6种核苷乙烯酯衍生物的均聚物。此外,通过酶促方法合成了核苷药物—PEG复合物。
Enzymatic methods play an important role in the synthesis of pharmaceutical compounds and their derivatives due to their high selectivity and mild reaction conditions. In this thesis, selective enzymatic synthesis of nucleoside drug derivatives was developed.
The selective enzymatic synthesis of some nucleoside derivatives containing multi-hydroxyl in non-aqueous media was developed. 2'-deoxy-5-fluorouridine, 5-fluorouridine, 5-fluorocytidine and 5'-deoxy-5-fluorouridine were chosen as substrates. Divinyl dicarboxylates with different length of carbon chain were used as acyl donor. Polymerizable vinyl esters derivatives of drugs were selectively prepared in good yields and selectivity through enzymatic reaction. Moreover, the influence factors of enzymatic synthesis such as enzyme sources, reaction media, water content, reaction time, temperature were investigated.
The controllable selective synthesis of 2'-deoxy-5-fluorouridine derivatives could be achieved. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in THF or alkaline protease from Bacillus subtilis (Subtilisin) in pyridine could facilitate the single step synthesis of polymerizable 2'-deoxy-5-fluorouridine derivatives in high yields. The controllable selectivity of different position of 2'-deoxy-5-fluorouridine was achieved by change reaction conditions. Furthermore, selective acylation of primary hydroxyl of 5-fluorouridine and 5-fluorocytidine was achieved. The reaction was catalyzed by CAL-B in THF. And the enzymatic selective acylation of 5'-deoxy-5-fluorouridine was under investigation, too.
Floxuridine-saccharide and 5-fluorouridine conjugates, which are potential targeting drugs, were obtained from vinyl nucleoside esters by enzymatic methods. The reactions were catalyzed by Subtilisin in pyridine. The reactions were started from D-Glucose, D-Mannose, D-Galactose.
Synthesis of polymeric prodrugs of nucleosides was achieved by chemical polymerization initialed by AIBN in DMF. Moreover, nucleoside-PEG adducts were obtained by enzymatic methods. The reactions were initiated by CAL-B in THF.
本文发展了非水介质中含多羟基核苷类药物衍生物的酶促选择性合成方法。研究了2′-脱氧-5-氟尿苷、5-氟尿苷、5-氟胞苷和5′-脱氧-5-氟尿苷四种核苷类药物分别与四种具有不同链长的二酸二乙烯酯(C4,C6,C9,C10)的酶促反应,合成了新型的可聚合药物衍生物。同时考察酶源、反应介质、溶剂含水量、反应时间等各种因素对酶促酯交换反应产率和选择性的影响。反应具有条件温和、选择性高、产率好等特点。
论文研究了2′-脱氧-5-氟尿苷(FUDR)可聚合衍生物的可控制选择性合成。在THF中由固定化CAL-B或在吡啶中由Subtilisin催化的2′-脱氧-5-氟尿苷与二酸二乙烯酯的反应,选择性地发生在FUDR糖环的伯羟基位置;在THF中通过PSL-C催化的FUDR与二酸二乙烯酯的反应,可以得到仲羟基酰化的产物。即通过使用不同的酶实现了在FUDR的不同位置发生反应的选择性控制。5-氟尿苷、5-氟胞苷伯羟基的选择性酰化也成功地实现,选用的酶为CAL-B,溶剂为THF。本文也对5-氟胞苷和5′-脱氧-5-氟尿苷(DFUR)的两仲羟基的选择性进行了详细地研究,但由于两个仲羟基的化学环境太相似,选择性不太理想。
论文对核苷乙烯酯化合物进一步酶促衍生化,合成了一系列核苷类药物—糖类复合物。在吡啶中,用Subtilisin催化核苷乙烯酯衍生物和糖类(葡萄糖、甘露糖、半乳糖)的反应,选择性酰化糖类的特定羟基。其中药物—半乳糖复合物是潜在的靶向性药物。
论文在合成可聚合单体基础上,主要采用AIBN作为引发剂,DMF为反应溶剂合成了6种核苷乙烯酯衍生物的均聚物。此外,通过酶促方法合成了核苷药物—PEG复合物。
Enzymatic methods play an important role in the synthesis of pharmaceutical compounds and their derivatives due to their high selectivity and mild reaction conditions. In this thesis, selective enzymatic synthesis of nucleoside drug derivatives was developed.
The selective enzymatic synthesis of some nucleoside derivatives containing multi-hydroxyl in non-aqueous media was developed. 2'-deoxy-5-fluorouridine, 5-fluorouridine, 5-fluorocytidine and 5'-deoxy-5-fluorouridine were chosen as substrates. Divinyl dicarboxylates with different length of carbon chain were used as acyl donor. Polymerizable vinyl esters derivatives of drugs were selectively prepared in good yields and selectivity through enzymatic reaction. Moreover, the influence factors of enzymatic synthesis such as enzyme sources, reaction media, water content, reaction time, temperature were investigated.
The controllable selective synthesis of 2'-deoxy-5-fluorouridine derivatives could be achieved. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in THF or alkaline protease from Bacillus subtilis (Subtilisin) in pyridine could facilitate the single step synthesis of polymerizable 2'-deoxy-5-fluorouridine derivatives in high yields. The controllable selectivity of different position of 2'-deoxy-5-fluorouridine was achieved by change reaction conditions. Furthermore, selective acylation of primary hydroxyl of 5-fluorouridine and 5-fluorocytidine was achieved. The reaction was catalyzed by CAL-B in THF. And the enzymatic selective acylation of 5'-deoxy-5-fluorouridine was under investigation, too.
Floxuridine-saccharide and 5-fluorouridine conjugates, which are potential targeting drugs, were obtained from vinyl nucleoside esters by enzymatic methods. The reactions were catalyzed by Subtilisin in pyridine. The reactions were started from D-Glucose, D-Mannose, D-Galactose.
Synthesis of polymeric prodrugs of nucleosides was achieved by chemical polymerization initialed by AIBN in DMF. Moreover, nucleoside-PEG adducts were obtained by enzymatic methods. The reactions were initiated by CAL-B in THF.
引文
[1]Zaks A,Klibanov A.M.,Science,1984,224:1249
[2]张玉彬,生物催化的手性合成,化学工业出版社,北京,2002
[3]Mozhaev V.V.,Budde C.L.,Rich J.O.,Tetrahedron,1998,3971
[4]尤启东 主编 药物化学,化学工业出版社,北京,2004
[5]曾苏 主编,手性药物与手性药理学,浙江大学出版社,杭州,2002
[6]尤启冬,林国强主编 手性药物-研究与应用,化学工业出版社,北京,2004
[7]Wegman M.A.,Janssen M.H.A.,Sheldon R.A.,Adv.Synth.Catal.,2001:6-7,343
[8]Khmelnisky Y.L.,Budde C.,Arnold J.M.,et al.,J.Am.Chem.Soc.,1997,119:11554
[9]Riva S.,.Curr.Opin.Chem.Biol.,2001,5:106
[10]Garcia-Urdiales E.,Alfonso I.,Gotor V.,Chem.Rev.,2005,105:313
[11]Patel R.N.,Adv.Synth.Catal.,2001,6-7:343
[12]Liu C.F,Tam.J.R,Org.lett,2001,3:4157
[13]Liu Y.Y.,Xu J.H.,Hu Y.,J.,Viol.Catal.B:Enzym.,2000,10:523-529
[14]Cong F.D.,Wang Y.H.,Ma C.Y.,Enzyme Mierob.Technol.,2005,36:595
[15]姚日生 主编,药用高分子材料,化学工业出版社,北京,2003
[1]Drauz K.,Waldmann H.,Enzyme catalysis in organic synthesis,VCH publishers,1995
[2]Zaks A.,Klibanov A.M.,Science,1984,224:1249
[3]Carrea G.,Riva S.,Angew.Chem.Int.Ed.,2000,39:2226
[4]闫红,邢光建,胡娟等,化学研究与应用,2000,12:355
[5]V.Gotor,Org.Process Res.Dev.,2002,6,420-426
[6]罗贵民主编,酶工程,化学工业出版社,北京,2002
[7]Nowak I.,Jones C.T.,and Robins M.J.,J.Org.Chem.2006,71,3077-3081
[8]Serebryany V.;and Beigelman L.Tetrahedron Lett.,2002,43,1983-1985
[9]Maugard T.,Legoy M.D.,J.Mol.Catal.B:Enzym.,2000,8,275-280
[10]Maugard T.,Rejasse B.,Legoy M.D.,Biotechnol.Prog.2002,18,424-428
[11]Zhang D.H.,Bai S.,Sun Y.,FoodChem.,2007,102,1012-1019
[12]Baldessari A.,Mangone C.R,Biocatal.Biotransfor,2002,4:275
[13]Maugard T.,Tudella J.,Legoy M.D.,Biotechnol.Prog.2000,16,358-362
[14]Toyada-one Y.,Maeda M.,Nakao M.,et al.JOURNAL OF BIOSCIENCE AND BIOENGINEERING,2005,99,361-365.
[15]Ferrero M.,Gotor-Fernandez V.,J.Org.Chem.,1997,62:4358
[16]Wang Q.A.,Chem.Res.Chinese U.,2003,19:165
[17]Odinokov V.N.,Spivak A.Y.,Emelyanova G.A.,et al.,Russ.Chem.B+,2001,50:2121
[18]吴耀文,蒋宇扬,付华等,有机化学,2003,23,1091-1098
[19]Wang R,Dordick J.S.,Macromolecules,1998,31,941-943
[20]Li X.F.,Zong M.H.,Yang R.D.,J.Mol.Catal.B:Enzym.,2006,38,48-53
[21]Bergman A.M.,Kuiper C.M.,Voorn D.A.,et al.Biochem.Pharmacol.2004,67,503.
[22]TokiwaY.,Kitagawa M.,Fan H.,Yokochi T.,RakuT.,et al,Biotechnol.Tech.,1999,13,563-566
[23]Kitagawa M.,Fan H.,Raku T.,Kurane R.et al,Biotechnol.Lett.,2000,22,883-886
[24]Fan H.,Kitagawa M.,Raku T.,et al,Macromol.Biosci.2003,3,420-424
[25]Garcia J.,Diaz-Rodriguez A.,Fernandez S.,et al.J.Org.Chem.,2006,71,9765-9771
[26]Garcia J.,guez A.D.R.,Fernandez S.,et al.,Org.Lett.,2004,6,3759-3762
[27]Li X.F.,Lou W.Y.,Smith T.J.,et al.Green Chem.,2006,8,538-544
[28]Lav andera I.W.,Fernandez S.,Magdalena J.,et al.CHEMBIOCHEM,2005,6,1381-1390
[29]Diaz-Rodriguez A.,Fernandez S.,Lavandera I.,et al.Tetrahedron Lett.,2005,46,5835-5838
[30]Zinni M.A.,Rodriguez.SD.,Pontiggia RM,et al.J.Mol.Catal.B:Enzym.,2004,29,129-132
[31]Lavandera I.,Fernandez S.,Ferrero M.,et al.J.Org.Chem.,2001,66,4079-4082
[32]Ferrero M.,Gotor V.,Chem.Rev.,2000,100,4319
[33]Rich J.O.,Dordick J.S.,J.Am.Chem.Soc.,1997,119,3245-3252
[34]Iglesias L.E.,Zinni M.A.,Gallo M.,et al.Biotechnol.Lett.,2000,22,361-365
[35]Danieli B.,Luisetti M.,J.Org.Chem.1995,60,3637-3642
[36]Formica J.V.,Regelson W.,Food Chem.Toxicol.1995,33,1061
[37]Ishihara K.,Nakajima N.,J.Mol.Catal.B:Enzym.,2003,23,411-417
[38]Mellou F.,Loutrari H.,Stamatis H.,et al,Process Biochem.,2006,41,2029-2034
[39]Li D.,Park S.H.,Shim J.H.,Lee H.S.,Carbohydr.Res.,2004,339,2789-2797
[40]Akita H.,Kawahara E.,Kishida M.,J.Mol.Catal.B:Enzym.,2006,40,8-15
[41]Riva S.,J.Mol.Catal.B:Enzym.,2002,19-20,43-54
[42]Ardhaoui M.,Falcimaigne A.,Ognier S.,et al.,J.Biotechnol.,2004,110,265-271
[43]Khmelnitsky Y.L,Budde C.,Arnold J.M.,J.Am.Chem.Soc.,1997,119,11554
[44]Singh S.B.,Felock P.and Hazuda D.J.,Bioorg.Med.Chem.2000,10,235-238
[45]Nuria Armesto,Miguel Ferrero,Susana Fernandez,J.Org.Chem.2002,67,4978-4981
[46]Gu J.X.,Ruppen M.E.,Cai R,Org.Lett.,2005,7,151-157
[47]Friedman S.H.;DeCamp D.L.;Sijbesma R.P.;et al.J.Am.Chem.Soc.1993,115,6506-6509.
[48]Schergna S.,Ros T.D.,Linda P.,et al.Tetrahedron Lett.,1995,39,7791-7794
[49]Lohith K.,Vijayakumar G.R.,Somashekar B.R.et al.Eur.J.Med.Chem.,2006,41,1059-1072
[50]Wu Q.,Wang M.,Chen Z.C.,Enzyme Microb.Technol.,200639,1258-1263
[51]Wang N.,Wu Q.,Liu B.K.,J.Mol.Catal.B:Enzym.,2004,27,97-102
[52]Gotor,Moris,Synthesis,1992,626-628
[53]Lavandera,Susana et al,J.Org.Chem.2004,69,1748-1751
[54]Sundara,Taylor,Kang,Bowlin,Liu et al,Lanct 1989,1206
[55]Margolin A.L.,Delinck D.L.,Whalo M.R.,J.Am.Chem.Soc.,1990,112,8
[56]Mozhaev V.V.,Budde C.L.,Rich J.O.,Tetrahedron,1998,54,3971-3982
[57]Quan J.,Wang N.,Cai X.Q.et al.J.Mol.Catal.B:Enzym.,2007,44,1-7
[58]X.Li,Qi Wu,De-shui Lv et al.Bioorg.Med.Chem.,2006,14,3377-3382
[59]Sun X.F.,Wang,N.Wu Q.et al.Biotechnol.Lett.,2004,26,1019-1022
[60]Wang N.,Chen Z.C.,L D.S.u,et al.Bioorg.Med.Chem.,2005,15,4064-4067
[61]Ward,R.S.Tetrahedron:Asymmetry,1995,6,1475.
[62]Noyori,R.;Tokunaga,M.;Kitamura,M.Bull.Chem.Soc.Jpn.1995,68,36.
[63]Caddick,S.;Jenkins,K.Chem.Soc.Rev.1996,25,447.
[64]Stecher,H.;Faber,K.Synthesis 1997,1.
[65]Kim,M.J.;Aim,Y.;Park,J.Curr.Opin.Biotechno1 2002,13,578.
[66]Parnies O.,Backvall J.E.Chem.Rev.2003,103,3247-3261
[67]Lee T.,Sakowicz R.,Martichonoc V.,et al.,Aacta.Chem.Scand.,1996,50,697-706
[68]Kazlauskas R.J.,Weissfloch A.N.E.,Rappaport A.T.,et al.J.Org.Chem.1991,56,2656.
[69]Ghanem A.,Aboul-Enein H.Y.,Chirality,2005,17,1-15
[70]Schmid A.,Dordick J.S.,Hauer B.,et al.,NATURE,2001,409,258-268
[71]Chert J.C.,Ysai S.,Biotechnol.Prog.2000,16,986-992
[72]Chang C.S.,Su C.C.,Zhuang J.R.,Tsai S.W.,J.Mol.Catal.B:Entre.,2004,30,151-157
[73]Hanson R.L.,Parker W.L.,Brzozowski D.B.,et al.Tetrahedron:Asymmetry,2005,16,2711-2716
[74]Manam R.R.,Macherla V.R.,Potts B.C.M.,et al.,Tetrahedron Lett.,2007,48,2537-2540
[75]D.S.Im,C.S.Cheong,Lee S.H.,J.Mol.Catal.B:Enzym.,2003,26,185-191
[76]Solares L.F.,Brieva R.,Quirios M.,et al.Tetrahedron:Asymmetry,2004,15,341-345
[77]Truppo M.D.,Journet M.,Shafiee A.,et al.Org.Process Res.Dev.2006,10,592-598
[78]Pinot E.,Guy A.,Guyon A.L.,et al.Tetrahedron:Asymmetry,2005,16,1893-1895
[79]Park O.J.,Lee S.H.,Park T.Y.,et al.Org.Process Res.Dev.,2006,10,588-591
[80]Atuu M.R.,Hossain M.M.,Tetrahedron Lett.,2007,48,3875-3878
[81]Regla I.,Luna H.,Perez H.I.,Tetrahedron:Asymmetry,2004,15,1285-1288
[82]Carboni C.,Kierkels H.G.T.,Gardossi L.,et al.Tetrahedron:Asymmetry,2006,17,245-251
[83]Sanchez P.F.,Escalante J.,Castillo E.,Tetrahedron:Asymmetry,2005,16,629-634
[84]Monfort N.,Archelas A.,Furstoss R.,Tetrahedron,2004,60,601-605
[85]Mehta G.,Islam K.,Tetrahedron Lett.,2004,45,7683-7687
[86]Betts R.L.,Murphy S.Y.,Johnson C.R.,Tetrahedron:Asymmetry,2004,15,2853-2860
[87]Karboune S.,Archelas A.,Furstoss R.,et al.J.Mol.Catal.B:Enzym.,2005,32,175-183
[88]Jeffrey H.Lutje Spelberg,a Lixia Tang,et al.Tetrahedron:Asymmetry,2004,15,1095-1102
[89]Patel R.,Banerjee A.,Howell J.,et al.Tetrahedron:Asymmetry,1993,4,2069-2084.
[90]Patel R.,Banerjee A.,Ko R.,et al.Biotechnol.Appl.Biochem.1994,20,23-33.
[1]汤雁波,李卓荣,中国生化药物杂志,2004,25:44
[2]李庶心,王志清,胡文祥等,中国药物化学杂志,1996,6:214
[3]Ballotore C.,McGuigan C.,Clercq E.,et al.,Bioorg.Med.Chem.Lett.,2001.11:1053
[4]Riva S.,Chopineau J.,Kieboom A.P.G.,et al.,J.Am.Chem.Sot.,1988,110:584
[5]Hanson R.L.,Shi Z.,Brzozowski D.B.,et al.,Bioorg.Med.Chem.,2000,8:2681
[6]Ferrero M.,Gotor V.,Chem.Rev.,2000,100:4319
[7]Kitagawa M.,Fan H.,Raku T.,et al,Biotechnol.Lett.,2000,22:883-886
[8]Tokiwa Y.,Kitagawa M.,Fan H.,et al.,Biotechnol.Tech.,1999,13:563
[9]Fan H.,Kitagawa M.,Raku T.,et al.,Biochem.Eng.J.,2004,21:279
[10]a)Liu B.K.,Wang N.,Wu Q.,et al.,Biotechnol.Lett.,2005,27:717
b)Sun X.F.,Wang N.,Wu Q.,et al.,Biotechnol.Lett.,2004,26:1019
[11]Sun X.F.,Wu Q.,Wang N.et al.,Biotechnol.Lett.,2005,27:113
[12]Wang N.,Chen Z.C.,Lu D.S.et al.,Bioorg.Med.Chem.Lett.,2005,15:4064
[13]ohn E.D.,Henry W.S.,Robert J.P.,British Patent.1960,827718
[14]Duschinsky R.,Gabriel Y.,Hoffer M.et al.J.Med.Chem.,1966,9,566-572
[15]Yoshimoto K.,Itatani Y.,Tsuda Y.,Chem.Pharm.Bull.,1980,28:2065.
[16]Knubovets T.,Osterhout J.J.,Klibanov A.M.,BiotechnoL Bioeng.,1999.63.242-248
[17]Laane C.,Boeren S.,Vos K.,et al J.Biotechnol.Bioeng.,1987,30,81-87
[18]Xu Z.F.,Ameek R.,Wangikar P.,et al.J.Biotechnol Bioeng,1994,43,515-520
[19].Laane C.,Boeren S.,Vos K.,Trands Biotechnol.,1985,3:251
[20].Laane C.,Boeren S.,Vos K.,et al.,Biotechnol.Bioeng.,1987,30:81
[21].Zaks A.,Klibanov A.M.,J.Biolog.Chem.,1988,263,8017-8021
[22].Cook A.E,Holman M.J.,Kramer M.,J.et al.J.Med.Chem.,1979,22,1330-1335
[1]Maeder T.,SCIENTIFIC AMERICAN,2002,287(1),40-47
[2]Anwer K.,Bailey A.,Sullivan,S.M.Crit.Rev.Ther.Drug.Carr.Sys.,2000,17,377
[3]Quan J.,Chen Z.C.,Han C.Y.,et al.,Bioorg.Med.Chem.,2007,15,1741-1748
[4]Wu Q.,Wang M.,.Chen Z.C.,et al.,Enzyme Microb.Technol.,2006,39,1258-1263
[5]..Xu J.M.,.Yao S.P,.Wu W.B,J.Mol.Catal.B:Enzym.,2005,35,122-127
[6]Khmelnitsky Y.L,Budde C.,Arnold J.M.,J.Am.Chem.Soc.,1997,119,11554
[1]关燕清,邱李莉,廖瑞雪等,华南师范大学学报,2005,2,126-134
[2]Greish K.,Sawa T.,Fang J.,et al.,J.Controlled Release,2004,97,219-231
[3]Giunchedi P.,Genta I.,Conti B.,et al.,Biomaterials,1998,19,157
[4]张修建,王清明,陈惠鹏等,解放军药学学报,2003,19,213-216。
[5]Gabizon A.,Martin F.,Drugs,1997,54,15
[6]Harrington K.J.,Mohammadtaghi S.,Uster P.S.,et al.,Clin.Cancer Res.,2001,7,243
[7]Kozlowski A.,Van Ea T.,Palczuk N.C.,et al.,J.Biol.Chem.,1977,252,3578
[8]Abuchowski A.,Kazo G.M.,Verhoest C.R.,et al.,Cancer Biochem.Biopys.,1984,7,175
[9]Takac M.S.,Jacobs S.J.,et al.,J.Interferon Cytokine Res.,1999,19,781
[10]Reddy K.R.,Ann.Pharmacother,2000,34,915
[2]张玉彬,生物催化的手性合成,化学工业出版社,北京,2002
[3]Mozhaev V.V.,Budde C.L.,Rich J.O.,Tetrahedron,1998,3971
[4]尤启东 主编 药物化学,化学工业出版社,北京,2004
[5]曾苏 主编,手性药物与手性药理学,浙江大学出版社,杭州,2002
[6]尤启冬,林国强主编 手性药物-研究与应用,化学工业出版社,北京,2004
[7]Wegman M.A.,Janssen M.H.A.,Sheldon R.A.,Adv.Synth.Catal.,2001:6-7,343
[8]Khmelnisky Y.L.,Budde C.,Arnold J.M.,et al.,J.Am.Chem.Soc.,1997,119:11554
[9]Riva S.,.Curr.Opin.Chem.Biol.,2001,5:106
[10]Garcia-Urdiales E.,Alfonso I.,Gotor V.,Chem.Rev.,2005,105:313
[11]Patel R.N.,Adv.Synth.Catal.,2001,6-7:343
[12]Liu C.F,Tam.J.R,Org.lett,2001,3:4157
[13]Liu Y.Y.,Xu J.H.,Hu Y.,J.,Viol.Catal.B:Enzym.,2000,10:523-529
[14]Cong F.D.,Wang Y.H.,Ma C.Y.,Enzyme Mierob.Technol.,2005,36:595
[15]姚日生 主编,药用高分子材料,化学工业出版社,北京,2003
[1]Drauz K.,Waldmann H.,Enzyme catalysis in organic synthesis,VCH publishers,1995
[2]Zaks A.,Klibanov A.M.,Science,1984,224:1249
[3]Carrea G.,Riva S.,Angew.Chem.Int.Ed.,2000,39:2226
[4]闫红,邢光建,胡娟等,化学研究与应用,2000,12:355
[5]V.Gotor,Org.Process Res.Dev.,2002,6,420-426
[6]罗贵民主编,酶工程,化学工业出版社,北京,2002
[7]Nowak I.,Jones C.T.,and Robins M.J.,J.Org.Chem.2006,71,3077-3081
[8]Serebryany V.;and Beigelman L.Tetrahedron Lett.,2002,43,1983-1985
[9]Maugard T.,Legoy M.D.,J.Mol.Catal.B:Enzym.,2000,8,275-280
[10]Maugard T.,Rejasse B.,Legoy M.D.,Biotechnol.Prog.2002,18,424-428
[11]Zhang D.H.,Bai S.,Sun Y.,FoodChem.,2007,102,1012-1019
[12]Baldessari A.,Mangone C.R,Biocatal.Biotransfor,2002,4:275
[13]Maugard T.,Tudella J.,Legoy M.D.,Biotechnol.Prog.2000,16,358-362
[14]Toyada-one Y.,Maeda M.,Nakao M.,et al.JOURNAL OF BIOSCIENCE AND BIOENGINEERING,2005,99,361-365.
[15]Ferrero M.,Gotor-Fernandez V.,J.Org.Chem.,1997,62:4358
[16]Wang Q.A.,Chem.Res.Chinese U.,2003,19:165
[17]Odinokov V.N.,Spivak A.Y.,Emelyanova G.A.,et al.,Russ.Chem.B+,2001,50:2121
[18]吴耀文,蒋宇扬,付华等,有机化学,2003,23,1091-1098
[19]Wang R,Dordick J.S.,Macromolecules,1998,31,941-943
[20]Li X.F.,Zong M.H.,Yang R.D.,J.Mol.Catal.B:Enzym.,2006,38,48-53
[21]Bergman A.M.,Kuiper C.M.,Voorn D.A.,et al.Biochem.Pharmacol.2004,67,503.
[22]TokiwaY.,Kitagawa M.,Fan H.,Yokochi T.,RakuT.,et al,Biotechnol.Tech.,1999,13,563-566
[23]Kitagawa M.,Fan H.,Raku T.,Kurane R.et al,Biotechnol.Lett.,2000,22,883-886
[24]Fan H.,Kitagawa M.,Raku T.,et al,Macromol.Biosci.2003,3,420-424
[25]Garcia J.,Diaz-Rodriguez A.,Fernandez S.,et al.J.Org.Chem.,2006,71,9765-9771
[26]Garcia J.,guez A.D.R.,Fernandez S.,et al.,Org.Lett.,2004,6,3759-3762
[27]Li X.F.,Lou W.Y.,Smith T.J.,et al.Green Chem.,2006,8,538-544
[28]Lav andera I.W.,Fernandez S.,Magdalena J.,et al.CHEMBIOCHEM,2005,6,1381-1390
[29]Diaz-Rodriguez A.,Fernandez S.,Lavandera I.,et al.Tetrahedron Lett.,2005,46,5835-5838
[30]Zinni M.A.,Rodriguez.SD.,Pontiggia RM,et al.J.Mol.Catal.B:Enzym.,2004,29,129-132
[31]Lavandera I.,Fernandez S.,Ferrero M.,et al.J.Org.Chem.,2001,66,4079-4082
[32]Ferrero M.,Gotor V.,Chem.Rev.,2000,100,4319
[33]Rich J.O.,Dordick J.S.,J.Am.Chem.Soc.,1997,119,3245-3252
[34]Iglesias L.E.,Zinni M.A.,Gallo M.,et al.Biotechnol.Lett.,2000,22,361-365
[35]Danieli B.,Luisetti M.,J.Org.Chem.1995,60,3637-3642
[36]Formica J.V.,Regelson W.,Food Chem.Toxicol.1995,33,1061
[37]Ishihara K.,Nakajima N.,J.Mol.Catal.B:Enzym.,2003,23,411-417
[38]Mellou F.,Loutrari H.,Stamatis H.,et al,Process Biochem.,2006,41,2029-2034
[39]Li D.,Park S.H.,Shim J.H.,Lee H.S.,Carbohydr.Res.,2004,339,2789-2797
[40]Akita H.,Kawahara E.,Kishida M.,J.Mol.Catal.B:Enzym.,2006,40,8-15
[41]Riva S.,J.Mol.Catal.B:Enzym.,2002,19-20,43-54
[42]Ardhaoui M.,Falcimaigne A.,Ognier S.,et al.,J.Biotechnol.,2004,110,265-271
[43]Khmelnitsky Y.L,Budde C.,Arnold J.M.,J.Am.Chem.Soc.,1997,119,11554
[44]Singh S.B.,Felock P.and Hazuda D.J.,Bioorg.Med.Chem.2000,10,235-238
[45]Nuria Armesto,Miguel Ferrero,Susana Fernandez,J.Org.Chem.2002,67,4978-4981
[46]Gu J.X.,Ruppen M.E.,Cai R,Org.Lett.,2005,7,151-157
[47]Friedman S.H.;DeCamp D.L.;Sijbesma R.P.;et al.J.Am.Chem.Soc.1993,115,6506-6509.
[48]Schergna S.,Ros T.D.,Linda P.,et al.Tetrahedron Lett.,1995,39,7791-7794
[49]Lohith K.,Vijayakumar G.R.,Somashekar B.R.et al.Eur.J.Med.Chem.,2006,41,1059-1072
[50]Wu Q.,Wang M.,Chen Z.C.,Enzyme Microb.Technol.,200639,1258-1263
[51]Wang N.,Wu Q.,Liu B.K.,J.Mol.Catal.B:Enzym.,2004,27,97-102
[52]Gotor,Moris,Synthesis,1992,626-628
[53]Lavandera,Susana et al,J.Org.Chem.2004,69,1748-1751
[54]Sundara,Taylor,Kang,Bowlin,Liu et al,Lanct 1989,1206
[55]Margolin A.L.,Delinck D.L.,Whalo M.R.,J.Am.Chem.Soc.,1990,112,8
[56]Mozhaev V.V.,Budde C.L.,Rich J.O.,Tetrahedron,1998,54,3971-3982
[57]Quan J.,Wang N.,Cai X.Q.et al.J.Mol.Catal.B:Enzym.,2007,44,1-7
[58]X.Li,Qi Wu,De-shui Lv et al.Bioorg.Med.Chem.,2006,14,3377-3382
[59]Sun X.F.,Wang,N.Wu Q.et al.Biotechnol.Lett.,2004,26,1019-1022
[60]Wang N.,Chen Z.C.,L D.S.u,et al.Bioorg.Med.Chem.,2005,15,4064-4067
[61]Ward,R.S.Tetrahedron:Asymmetry,1995,6,1475.
[62]Noyori,R.;Tokunaga,M.;Kitamura,M.Bull.Chem.Soc.Jpn.1995,68,36.
[63]Caddick,S.;Jenkins,K.Chem.Soc.Rev.1996,25,447.
[64]Stecher,H.;Faber,K.Synthesis 1997,1.
[65]Kim,M.J.;Aim,Y.;Park,J.Curr.Opin.Biotechno1 2002,13,578.
[66]Parnies O.,Backvall J.E.Chem.Rev.2003,103,3247-3261
[67]Lee T.,Sakowicz R.,Martichonoc V.,et al.,Aacta.Chem.Scand.,1996,50,697-706
[68]Kazlauskas R.J.,Weissfloch A.N.E.,Rappaport A.T.,et al.J.Org.Chem.1991,56,2656.
[69]Ghanem A.,Aboul-Enein H.Y.,Chirality,2005,17,1-15
[70]Schmid A.,Dordick J.S.,Hauer B.,et al.,NATURE,2001,409,258-268
[71]Chert J.C.,Ysai S.,Biotechnol.Prog.2000,16,986-992
[72]Chang C.S.,Su C.C.,Zhuang J.R.,Tsai S.W.,J.Mol.Catal.B:Entre.,2004,30,151-157
[73]Hanson R.L.,Parker W.L.,Brzozowski D.B.,et al.Tetrahedron:Asymmetry,2005,16,2711-2716
[74]Manam R.R.,Macherla V.R.,Potts B.C.M.,et al.,Tetrahedron Lett.,2007,48,2537-2540
[75]D.S.Im,C.S.Cheong,Lee S.H.,J.Mol.Catal.B:Enzym.,2003,26,185-191
[76]Solares L.F.,Brieva R.,Quirios M.,et al.Tetrahedron:Asymmetry,2004,15,341-345
[77]Truppo M.D.,Journet M.,Shafiee A.,et al.Org.Process Res.Dev.2006,10,592-598
[78]Pinot E.,Guy A.,Guyon A.L.,et al.Tetrahedron:Asymmetry,2005,16,1893-1895
[79]Park O.J.,Lee S.H.,Park T.Y.,et al.Org.Process Res.Dev.,2006,10,588-591
[80]Atuu M.R.,Hossain M.M.,Tetrahedron Lett.,2007,48,3875-3878
[81]Regla I.,Luna H.,Perez H.I.,Tetrahedron:Asymmetry,2004,15,1285-1288
[82]Carboni C.,Kierkels H.G.T.,Gardossi L.,et al.Tetrahedron:Asymmetry,2006,17,245-251
[83]Sanchez P.F.,Escalante J.,Castillo E.,Tetrahedron:Asymmetry,2005,16,629-634
[84]Monfort N.,Archelas A.,Furstoss R.,Tetrahedron,2004,60,601-605
[85]Mehta G.,Islam K.,Tetrahedron Lett.,2004,45,7683-7687
[86]Betts R.L.,Murphy S.Y.,Johnson C.R.,Tetrahedron:Asymmetry,2004,15,2853-2860
[87]Karboune S.,Archelas A.,Furstoss R.,et al.J.Mol.Catal.B:Enzym.,2005,32,175-183
[88]Jeffrey H.Lutje Spelberg,a Lixia Tang,et al.Tetrahedron:Asymmetry,2004,15,1095-1102
[89]Patel R.,Banerjee A.,Howell J.,et al.Tetrahedron:Asymmetry,1993,4,2069-2084.
[90]Patel R.,Banerjee A.,Ko R.,et al.Biotechnol.Appl.Biochem.1994,20,23-33.
[1]汤雁波,李卓荣,中国生化药物杂志,2004,25:44
[2]李庶心,王志清,胡文祥等,中国药物化学杂志,1996,6:214
[3]Ballotore C.,McGuigan C.,Clercq E.,et al.,Bioorg.Med.Chem.Lett.,2001.11:1053
[4]Riva S.,Chopineau J.,Kieboom A.P.G.,et al.,J.Am.Chem.Sot.,1988,110:584
[5]Hanson R.L.,Shi Z.,Brzozowski D.B.,et al.,Bioorg.Med.Chem.,2000,8:2681
[6]Ferrero M.,Gotor V.,Chem.Rev.,2000,100:4319
[7]Kitagawa M.,Fan H.,Raku T.,et al,Biotechnol.Lett.,2000,22:883-886
[8]Tokiwa Y.,Kitagawa M.,Fan H.,et al.,Biotechnol.Tech.,1999,13:563
[9]Fan H.,Kitagawa M.,Raku T.,et al.,Biochem.Eng.J.,2004,21:279
[10]a)Liu B.K.,Wang N.,Wu Q.,et al.,Biotechnol.Lett.,2005,27:717
b)Sun X.F.,Wang N.,Wu Q.,et al.,Biotechnol.Lett.,2004,26:1019
[11]Sun X.F.,Wu Q.,Wang N.et al.,Biotechnol.Lett.,2005,27:113
[12]Wang N.,Chen Z.C.,Lu D.S.et al.,Bioorg.Med.Chem.Lett.,2005,15:4064
[13]ohn E.D.,Henry W.S.,Robert J.P.,British Patent.1960,827718
[14]Duschinsky R.,Gabriel Y.,Hoffer M.et al.J.Med.Chem.,1966,9,566-572
[15]Yoshimoto K.,Itatani Y.,Tsuda Y.,Chem.Pharm.Bull.,1980,28:2065.
[16]Knubovets T.,Osterhout J.J.,Klibanov A.M.,BiotechnoL Bioeng.,1999.63.242-248
[17]Laane C.,Boeren S.,Vos K.,et al J.Biotechnol.Bioeng.,1987,30,81-87
[18]Xu Z.F.,Ameek R.,Wangikar P.,et al.J.Biotechnol Bioeng,1994,43,515-520
[19].Laane C.,Boeren S.,Vos K.,Trands Biotechnol.,1985,3:251
[20].Laane C.,Boeren S.,Vos K.,et al.,Biotechnol.Bioeng.,1987,30:81
[21].Zaks A.,Klibanov A.M.,J.Biolog.Chem.,1988,263,8017-8021
[22].Cook A.E,Holman M.J.,Kramer M.,J.et al.J.Med.Chem.,1979,22,1330-1335
[1]Maeder T.,SCIENTIFIC AMERICAN,2002,287(1),40-47
[2]Anwer K.,Bailey A.,Sullivan,S.M.Crit.Rev.Ther.Drug.Carr.Sys.,2000,17,377
[3]Quan J.,Chen Z.C.,Han C.Y.,et al.,Bioorg.Med.Chem.,2007,15,1741-1748
[4]Wu Q.,Wang M.,.Chen Z.C.,et al.,Enzyme Microb.Technol.,2006,39,1258-1263
[5]..Xu J.M.,.Yao S.P,.Wu W.B,J.Mol.Catal.B:Enzym.,2005,35,122-127
[6]Khmelnitsky Y.L,Budde C.,Arnold J.M.,J.Am.Chem.Soc.,1997,119,11554
[1]关燕清,邱李莉,廖瑞雪等,华南师范大学学报,2005,2,126-134
[2]Greish K.,Sawa T.,Fang J.,et al.,J.Controlled Release,2004,97,219-231
[3]Giunchedi P.,Genta I.,Conti B.,et al.,Biomaterials,1998,19,157
[4]张修建,王清明,陈惠鹏等,解放军药学学报,2003,19,213-216。
[5]Gabizon A.,Martin F.,Drugs,1997,54,15
[6]Harrington K.J.,Mohammadtaghi S.,Uster P.S.,et al.,Clin.Cancer Res.,2001,7,243
[7]Kozlowski A.,Van Ea T.,Palczuk N.C.,et al.,J.Biol.Chem.,1977,252,3578
[8]Abuchowski A.,Kazo G.M.,Verhoest C.R.,et al.,Cancer Biochem.Biopys.,1984,7,175
[9]Takac M.S.,Jacobs S.J.,et al.,J.Interferon Cytokine Res.,1999,19,781
[10]Reddy K.R.,Ann.Pharmacother,2000,34,915