布林佐胺的化学合成、手性分析与结构修饰
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摘要
布林佐胺是一种局部碳酸酐酶抑制剂,具有高效低毒、副作用小的优点,已经成为治疗开角型青光眼的一线药物。
本论文在简述布林佐胺合成进展的基础上,拟定布林佐胺的合成路线,同时分析比较了各步单元反应的方法。从3-溴代乙酰基-5-氯-2-噻吩磺酰胺出发,经过不对称还原、关环、N-烃基化、亚硫酸化、磺胺化、胺基保护、胺化等七步反应制得布林佐胺。优化了工艺条件,路线总产率达到29%。通过分析实验现象和实验数据,推测了各步反应的可能历程。
用类似方法合成了(S)-布林佐胺,七步反应总产率23%；将其与布林佐胺按1∶1混合并进行HPLC分析,筛选出分离效果较佳的液相色谱柱(Chiralpak AD-H),并优化了测试条件,结果表明：布林佐胺的纯度为99.86%,e.e.值接近100%。HPLC验证了(+)-二异松蒎基氯硼烷在不对称还原关环反应中具有较优的手性选择性：中间产物5的纯度为98.91%,e.e.值为97.81%。
针对布林佐胺存在的作用时间短、水溶性差、有眼部刺激等不足,在结构修饰成功案例的基础上,依据药物设计相关原理提出结构修饰方案,合成了5个具有潜在药物活性的布林佐胺类似物。
Brinzolamide is a topical carbonic anhydrase inhibitor. The well curative effects, tiny toxicity and small side effects of Brinzolamide make it an important medicine for curing open angle glaucoma.
In this thesis, the preparative methods of Brinzolamide were briefly reviewed, and then the synthetic route of Brinzolamide was designed. The methods of each step in the synthetic route were summarized and compared. Brinzolamide was synthesized from 3-(2-bromoacetyl)-5-chloro-2-thiophenesulfonamide through seven-step reactions, including asymmetric reduction, cyclization, N-alkylation, sulfitation, sulfamation, amino protection and amination. The reactive conditions were optimized in overall yield of 29%. According to the phenomenon and data,the reasonable mechanism of the reactions was presumed respectively.
Brinzolamide (S)-isomer was synthesized in similar methods through seven-step reactions in overall yield of 23%.The mixture of brinzolamide and its (S)-isomer, on the ratio 1/1,was analyzed by HPLC, so that the column with ideal resolution factor was screened out, and the test conditions were optimized. The results showed that the purity and e.e. value of synthesized Brinzolamide were 99.86% and 100% respectively. The purity and e.e.value of product compound 5 were 98.91% and 97.81% through HPLC analysis respectively, which showed the excellent chiral selectivity of (+)-Ipc2BCl in related reaction.
Considering the disadvantages of Brinzolamide, such as short effective time, poor water-solubility, and eye irritating reaction, the plan of structural modification was proposed on the basis of successful cases and the theoretics of drug design. Five analogs of Brinzolamide with potential biological activity were synthesized.
本论文在简述布林佐胺合成进展的基础上,拟定布林佐胺的合成路线,同时分析比较了各步单元反应的方法。从3-溴代乙酰基-5-氯-2-噻吩磺酰胺出发,经过不对称还原、关环、N-烃基化、亚硫酸化、磺胺化、胺基保护、胺化等七步反应制得布林佐胺。优化了工艺条件,路线总产率达到29%。通过分析实验现象和实验数据,推测了各步反应的可能历程。
用类似方法合成了(S)-布林佐胺,七步反应总产率23%；将其与布林佐胺按1∶1混合并进行HPLC分析,筛选出分离效果较佳的液相色谱柱(Chiralpak AD-H),并优化了测试条件,结果表明：布林佐胺的纯度为99.86%,e.e.值接近100%。HPLC验证了(+)-二异松蒎基氯硼烷在不对称还原关环反应中具有较优的手性选择性：中间产物5的纯度为98.91%,e.e.值为97.81%。
针对布林佐胺存在的作用时间短、水溶性差、有眼部刺激等不足,在结构修饰成功案例的基础上,依据药物设计相关原理提出结构修饰方案,合成了5个具有潜在药物活性的布林佐胺类似物。
Brinzolamide is a topical carbonic anhydrase inhibitor. The well curative effects, tiny toxicity and small side effects of Brinzolamide make it an important medicine for curing open angle glaucoma.
In this thesis, the preparative methods of Brinzolamide were briefly reviewed, and then the synthetic route of Brinzolamide was designed. The methods of each step in the synthetic route were summarized and compared. Brinzolamide was synthesized from 3-(2-bromoacetyl)-5-chloro-2-thiophenesulfonamide through seven-step reactions, including asymmetric reduction, cyclization, N-alkylation, sulfitation, sulfamation, amino protection and amination. The reactive conditions were optimized in overall yield of 29%. According to the phenomenon and data,the reasonable mechanism of the reactions was presumed respectively.
Brinzolamide (S)-isomer was synthesized in similar methods through seven-step reactions in overall yield of 23%.The mixture of brinzolamide and its (S)-isomer, on the ratio 1/1,was analyzed by HPLC, so that the column with ideal resolution factor was screened out, and the test conditions were optimized. The results showed that the purity and e.e. value of synthesized Brinzolamide were 99.86% and 100% respectively. The purity and e.e.value of product compound 5 were 98.91% and 97.81% through HPLC analysis respectively, which showed the excellent chiral selectivity of (+)-Ipc2BCl in related reaction.
Considering the disadvantages of Brinzolamide, such as short effective time, poor water-solubility, and eye irritating reaction, the plan of structural modification was proposed on the basis of successful cases and the theoretics of drug design. Five analogs of Brinzolamide with potential biological activity were synthesized.
引文
[1]Quigley H A, Broman A T. The Number of People with Glaucoma Worldwide in 2010 and 2020.The British Journal of Ophthalmology,2006,90:262-267.
[2]唐细兰,黄楚龙,余敏斌.青光眼药物治疗进展.中国药学杂志,2005,18(40)：1369-1372.
[3]贾洪亮.抗青光眼药物的分类及其临床应用.现代诊断与治疗,2008,19(4)：244-245.
[4]Raymond P, LeBlanc M D.Twelve-month Results of an Ongoing Randomized Trial Comparing Brimonidine Tartrate 0.2% and Timolol 0.5% Given Twice Daily in Patients with Glaucoma or Ocular Hypertension. Ophthalmology,1998,105(10):1960-1967.
[5]Donello J E, Padillo E U, Webster M L, et al.a2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia. The Journal of Pharmacology and Experimental Therapeutics,2001,296: 216-223.
[6]韩继红.抗青光眼药物市场分析.河北化工,2008,31(4)：60-61.
[7]Thoms S.J. Hydrogen Bonds and the Catalytic Mechanism of Human Carbonic Anhydrase Ⅱ.Journal of Theoretical Biology,2002,215:399-404.
[8]Loferer M J, Tautermann C S,Loeffler H H, et al. Influence of Backbone Conformations of Human Carbonic Anhydrase Ⅱ on Carbon Dioxide Hydration:Hydration Pathways and Binding of Bicarbonate. Journal of American Chemical Society,2003,125: 8921-8927.
[9]Mafra D, Cozzolino S M F.Erythrocyte Zinc and Carbonic Anhydrase Levels in Nondialyzed Chronic Kidney Disease Patients. Clinical Biochemistry,2004,37:67-71.
[10]彭春霞,高艳明.碳酸酐酶生理功能的研究进展.北京大学学报(医学版),2007,39(2)：210-212.
[11]夏前明,钱桂生,黄坚,等.呼吸性酸碱失衡对家兔肾脏内髓集合管细胞碳酸酐酶活性及其表达的影响.第三军医大学学报,2000,22(9)：857-859.
[12]Comelia G, Gerolf G. Contractile Function of Papillary Muscles with Carbonic Anhydrase Inhibitors. Life Sciences,1995,57(6):591-597.
[13]Kuo W H, Yang S F, Hsieh Y S,et al. Differential Expression of Carbonic Anhydrase Isoenzymes in Various Types of Anemia. Clinica Chimica Acta,2005,351:79-86.
[14]Hunt J A, Ahmed M, Fierke C A. Metal Binding Specificity in Carbonic Anhydrase Is Influenced by Conserved Hydrophobic Core Residues.Biochemistry,1999,38:
9054-9062.
[15]姚忠,江程,李津申,等.用作抗青光眼药物的碳酸酐酶抑制剂.药学进展,2002,26(4)：202-205.
[16]Maren T H. Carbonic Anhydrase:General Perspectives and Advances in Glaucoma Research. Drug Development Research,1987,10:255-276.
[17]Wroblewski T, Graul A, Castaner J. Brinzolamide:Antiglaucoma Carbonic Anhydrase Inhibitor. Drugs of the Future,1998,23(4):365-369.
[18]Lindskog S.Structure and Mechanism of Carbonic Anhydrase. Pharmacology & Therapeutics,1997,74(1):1-20.
[19]徐岩,庞广仁,陈祖基.最新型局部碳酸酐酶抑制剂派立明的临床前及临床研究.眼科研究,2002,6(20)：560-564.
[20]DeSantis L. Preclinical Overview of Brinzolamide. Survey of Ophthalmology,2000, 44(S2):S119-S129.
[21]Shin D, the Brinzolamide Adjunctive Therapy Study Group. Adjunctive Therapy With Brinzolamide 1% Ophthalmic Suspension(Azopt(?))in Patients With Open-Angle Glaucoma or Ocular Hypertension Maintained on Timolol Therapy. Survey of Ophthalmology,2000,44(S2):S163-S168.
[22]Sall K, and the Brinzolamide Primary Therapy Study Group.The Efficacy and Safety of Brinzolamide 1% Ophthalmic Suspension (Azopt(?))as a Primary Therapy in Patients With Open-Angle Glaucoma or Ocular Hypertension. Survey of Ophthalmology,2000, 44(S2):S155-S162.
[23]Dean T R, Chen H H, May J A. Sulfonamides Useful as Carbonic Anhydrase Inhibitors. US:5378703,1995-01-03.
[24]Conrow R E, Dean W D, Zinke P W, et al. Enantioselective Synthesis of Brinzolamide(AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The "DCAT Route" to Thiophenesulfonamides. Organic Process Research & Development,1999,3 (2):114-120.
[25]Sathe D G, Tarur R V, Bhise N B.Improved process for the preparation of (R)-(+)-4-(ethylamino)-3,4-Dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfona mide-1,1-Dioxide. WO:2008062463,2008-05-29.
[26]Catasus A M, Garcia T J. Process for the Preparation of Brinzolamide and Intermediates Thereof. WO 2 008 132 114,2008-11-06.
[27]Brown H C, Chandrasekharan J, Ramachandranlb P V. Chiral Synthesis via Organoboranes.14. Selective Reductions.41.Diisopinocampheylchloroborane, an
Exceptionally Efficient Chiral Reducing Agent. Journal of American Chemical Society, 1988,110:1539-1546.
[28]Brown H C, Jadhavl P K. Asymmetric Carbon-Carbon Bond Formation via β-Allyldiisopinocampheylborane. Simple Synthesis of Secondary Homoallylic Alcohols with Excellent Enantiomeric Purities. Journal of American Chemical Society,1983,105: 2092-2093.
[29]Mori A, Yamamoto H. Diisopinocampheylchloroborane, a Remarkably Efficient Chiral Reducing Agent for Aromatic Prochiral Ketones.The Journal of Organic Chemistry, 1985,50:5446-5448.
[30]Takahashi T, Kanda Y, Nemoto H. Highly Efficient Asymmetric Reduction of a-Tertiary Alkyl Ketones with Diisopinocampheylchloroborane.The Journal of Organic Chemistry, 1986,51:3394-3396.
[31]Midland M M,Creer S, Tramontano A, et al.Chiral Trialkylborane Reducing Agents. Preparation of 1-Deuterio Primary Alcohols of High Enantiomeric Purity. Journal of American Chemical Society,1979,101(9):2352-2355.
[32]Midland M M, Kazubski A. NB-Enantride, a New Chiral Trialkylborohydride for the Asymmetric Reduction of Ketones. The Journal of Organic Chemistry,1982,47: 2496-2498.
[33]韦莹莹,王维德,赵鹏.酮类化合物的不对称还原.化工技术与开发,2010,39(1)：17-20.
[34]王维德,王宁辉,黄颖芬.酮的不对称还原研究进展.化学工业与工程,2007,24(3)：277-282.
[35]Masutani K, Uchida T, Irie R, et al. Catalytic Asymmetric and Chemoselective Aerobic Oxidation:Kinetic Resolution of Sec-alcohols. Tetrahedron Letters,2000(41): 5119-5123.
[36]胡艾希,曾昭琼.硼氢化锌在不对称合成中的应用.化学试剂,1989,11(1)：21-25,7.
[37]Noyori R, Tomino I, Tanimoto Y, et al.Rational Designing of Efficient Chiral Reducing Agents. Highly Enantioselective Reduction of Aromatic Ketones by Binaphthol-Modified Lithium Aluminum Hydride Reagents. Journal of American Chemical Society,1984,106:6709-6716.
[38]Ohkuma T, Ooka H, Hashiguchi S, et al. Practical Enantioselective Hydrogenation of Aromatic Ketones. Journal of American Chemical Society,1995,117:2675-2616.
[39]Deloux L, Srebnik M. Asymmetric Boron-Catalyzed Reactionst. Chemical Reviews, 1993,93:763-784.
[40]Bardot V, Besse P, Miahle Y G, et al.Microbial Synthesis of (+)-(3R)-Ethyl 3-hydroxy-3-(3,4-dimethoxyphenyl)propionate. Tetrahedron:Asymmetry,1996,7(4): 1077-1088.
[41]Molinari F, Occhiato E G, Aragozzini F. Microbial Biotransformations in Water/Organic Solvent System. Enantioselective Reduction of Aromatic β-and y-nitroketones. Tetrahedron:Asymmetry,1998,9:1389-1394.
[42]Elderfield R C, Craig L C, Lauer W M, et al.A Study of Plasmochin and the Occurrence of Rearrangements in the Preparation of Certain Plasmochin Analogs. Journal of American Chemical Society,1946,68(8):1516-1523.
[43]James B, Hendrickson, Bergeron R, et al.Triflamides for Protection and Monoalkylation of Amines and a New Gabriel Synthesis.Tetrahedron Letters,1973,14(39):3839-3842.
[44]Suga K, Watanabe S,Fujita T, et al.N-Alkylation of Primary and Secondary Amines by Alkyl Halides and Lithium Naphthalene. Bulletin of the Chemical Society of Japan, 1969,42(12):3606-3608.
[45]Gibson M S, Bradshaw R W. The Gabriel Synthesis of Primary Amines.Angewandte Chemie International Edition,1968,7(12):919-930.
[46]Snieckus V. Directed Ortho Metalation. Tertiary Amide and O-Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics.Chemical Reviews,1990,90: 879-933.
[47]Shinkai I. A Practical Asymmetric Synthesis of a Novel Topically Active Carbonic Anhydrase Inhibitor. Journal of Heterocyclic Chemistry,1992,29:627-630.
[48]Jones T K, Mohan J J, Xavier L C, et al. An asymmetric synthesis of MK-0417. Observations on oxazaborolidine-catalyzed reductions. The Journal of Organic Chemistry,1991,56(2):763-769.
[49]Tsai H J, Chou S Y, Chuang S H, et al. D-420720, A Novel Orally Active Sulfonamide Compound Dipeptidyl Peptidase IV Inhibitor:Structure and Activity Relationship of Arylsulfonamide to Dipeptidyl Peptidase IV Inhibition. Drug Development Research, 2008,69:514-519.
[50]Blacklock T J, Sohar P, Butcher J W, et al. An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507:5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride. The Journal of Organic Chemistry,1993,58(7):1672-1679.
[51]DuPriest M T, Zinke P W, Conrow R E, et al. Enantioselective Synthesis of AL-4414A, a Topically Active Carbonic Anhydrase Inhibitor. The Journal of Organic Chemistry, 1997,62:9372-9375.
[52]Baker R H, Dodson R M, Riegel B.The Cleavage of Organic Sulfides with Chlorine. Journal of American Chemical Society,1946,68:2636-2639.
[53]Kwart H, Miller R K. Chlorinolysis of Su(?)(?)(?)(?)-Carbon Bonds in Aryl-Alkyl Sulfides. Journal of American Chemical Society,1956,78:5008-5011.
[54]Remuzon P, Dussy C, Jacquet J P, et al.4-Hydroxy-2-Methyl-3(2H)-Isothiazolone-1, 1-Dioxide as Protecting Group of 4-(N-Methylaminosulfonyi) methyiphenyihydrazine during Fischer Indole Synthesis. Tetrahedron Letters,1995,36(35):6227-6230.
[55]Poss M A, Reid J A. The Use of Diphenylmethyl as a Sulfonamide Protecting Group. Tetrahedron Letters,1992,33(48):7291-7292.
[56]Szymonifka M J, Heck J V. The Synthesis and Reactions of 4-Carbomethoxy β-Syntams. Tetrahedron Letters,1989,30(22):2869-2872.
[57]Heck J V, Christensen B G. Nuclear Analogs of β-Lactam Antibiotics I.The synthesis of 6β-amidocyclonocardicins. Tetrahedron Letters,1981,22(50):5027-5030.
[58]Love B, Kormendy M F. N-Sulphonylimino Esters. Canadian Journal of Chemistry, 1964,42(1):176-178.
[59]Adkins H, Burgoyne E E, Schneide H J. The Copper-Chromium Oxide Catalyst for Hydrogenation. Journal of American Chemical Society,1950,72:2626-2629.
[60]张铸勇.精细有机合成单元反应.上海：华东理工大学出版社,2003,
[61]Edwards M L, Stemerick D M, McCarthy J R. Stereospecific Synthesis of Secondary Amines by the Mitsunobu Reaction. Tetrahedron Letters,1990,31(24):3417-3420.
[62]Scozzafava A, Briganti F, Mincione G, et al. Carbonic Anhydrase Inhibitors:Synthesis of Water-Soluble, Aminoacyl/Dipeptidyl Sulfonamides Possessing Long-Lasting Intraocular Pressure-Lowering Properties via the Topical Route. Journal of Medicinal Chemistry,1999,42:3690-3700.
[63]Supurana C T, Briganti F, Menabuoni L, et al. Carbonic anhydrase inhibitors-Part 78#. Synthesis of Water-soluble Sulfonamides Incorporating β-alanyl Moieties, Possessing Long Lasting-intraocular Pressure Lowering Properties via the Topical Route. European Journal of Medicinal Chemistry,2000,35:309-321.
[64]Scozzafava A, Menabuoni L, Mincione F, et al.Carbonic Anhydrase Inhibitors: Synthesis of Sulfonamides Incorporating Dtpa Tails and of Their Zinc Complexes with Powerful Topical Antiglaucoma Properties. Bioorganic & Medicinal Chemistry Letters, 2001,11:575-582.
[65]尤启东.药物化学.北京：化学工业出版社,2004,35-38.
[66]郭宗儒.药物化学总论.第二版.北京：中国医药科技出版社,2003,474-476.
[67]Gallagher D J, Beak P.Is Halogen-Lithium Exchange Intramolecularly Competitive with Removal of an Acidic Hydrogen? Reinvestigation of a Recent Claim. Journal of American Chemical Society,1991,113:7984-7987.
[68]Snieckus V. Directed Ortho Metalation. Tertiary Amide and & Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics. Chemical Reviews,1990,90: 879-933.
[69]Campagne J M. Total Syntheses of Lysobactin(Katanosin B). Angewandte Chemie International Edition,2007,46(45):8548-8552.
[70]Von Nussbaum F, Anlauf S,Benet-Buchholz J, et al.Structure and Total Synthesis of Lysobactin (Katanosin B).Angewandte Chemie International Edition,2007,46(12): 2039-2042.
[2]唐细兰,黄楚龙,余敏斌.青光眼药物治疗进展.中国药学杂志,2005,18(40)：1369-1372.
[3]贾洪亮.抗青光眼药物的分类及其临床应用.现代诊断与治疗,2008,19(4)：244-245.
[4]Raymond P, LeBlanc M D.Twelve-month Results of an Ongoing Randomized Trial Comparing Brimonidine Tartrate 0.2% and Timolol 0.5% Given Twice Daily in Patients with Glaucoma or Ocular Hypertension. Ophthalmology,1998,105(10):1960-1967.
[5]Donello J E, Padillo E U, Webster M L, et al.a2-Adrenoceptor Agonists Inhibit Vitreal Glutamate and Aspartate Accumulation and Preserve Retinal Function after Transient Ischemia. The Journal of Pharmacology and Experimental Therapeutics,2001,296: 216-223.
[6]韩继红.抗青光眼药物市场分析.河北化工,2008,31(4)：60-61.
[7]Thoms S.J. Hydrogen Bonds and the Catalytic Mechanism of Human Carbonic Anhydrase Ⅱ.Journal of Theoretical Biology,2002,215:399-404.
[8]Loferer M J, Tautermann C S,Loeffler H H, et al. Influence of Backbone Conformations of Human Carbonic Anhydrase Ⅱ on Carbon Dioxide Hydration:Hydration Pathways and Binding of Bicarbonate. Journal of American Chemical Society,2003,125: 8921-8927.
[9]Mafra D, Cozzolino S M F.Erythrocyte Zinc and Carbonic Anhydrase Levels in Nondialyzed Chronic Kidney Disease Patients. Clinical Biochemistry,2004,37:67-71.
[10]彭春霞,高艳明.碳酸酐酶生理功能的研究进展.北京大学学报(医学版),2007,39(2)：210-212.
[11]夏前明,钱桂生,黄坚,等.呼吸性酸碱失衡对家兔肾脏内髓集合管细胞碳酸酐酶活性及其表达的影响.第三军医大学学报,2000,22(9)：857-859.
[12]Comelia G, Gerolf G. Contractile Function of Papillary Muscles with Carbonic Anhydrase Inhibitors. Life Sciences,1995,57(6):591-597.
[13]Kuo W H, Yang S F, Hsieh Y S,et al. Differential Expression of Carbonic Anhydrase Isoenzymes in Various Types of Anemia. Clinica Chimica Acta,2005,351:79-86.
[14]Hunt J A, Ahmed M, Fierke C A. Metal Binding Specificity in Carbonic Anhydrase Is Influenced by Conserved Hydrophobic Core Residues.Biochemistry,1999,38:
9054-9062.
[15]姚忠,江程,李津申,等.用作抗青光眼药物的碳酸酐酶抑制剂.药学进展,2002,26(4)：202-205.
[16]Maren T H. Carbonic Anhydrase:General Perspectives and Advances in Glaucoma Research. Drug Development Research,1987,10:255-276.
[17]Wroblewski T, Graul A, Castaner J. Brinzolamide:Antiglaucoma Carbonic Anhydrase Inhibitor. Drugs of the Future,1998,23(4):365-369.
[18]Lindskog S.Structure and Mechanism of Carbonic Anhydrase. Pharmacology & Therapeutics,1997,74(1):1-20.
[19]徐岩,庞广仁,陈祖基.最新型局部碳酸酐酶抑制剂派立明的临床前及临床研究.眼科研究,2002,6(20)：560-564.
[20]DeSantis L. Preclinical Overview of Brinzolamide. Survey of Ophthalmology,2000, 44(S2):S119-S129.
[21]Shin D, the Brinzolamide Adjunctive Therapy Study Group. Adjunctive Therapy With Brinzolamide 1% Ophthalmic Suspension(Azopt(?))in Patients With Open-Angle Glaucoma or Ocular Hypertension Maintained on Timolol Therapy. Survey of Ophthalmology,2000,44(S2):S163-S168.
[22]Sall K, and the Brinzolamide Primary Therapy Study Group.The Efficacy and Safety of Brinzolamide 1% Ophthalmic Suspension (Azopt(?))as a Primary Therapy in Patients With Open-Angle Glaucoma or Ocular Hypertension. Survey of Ophthalmology,2000, 44(S2):S155-S162.
[23]Dean T R, Chen H H, May J A. Sulfonamides Useful as Carbonic Anhydrase Inhibitors. US:5378703,1995-01-03.
[24]Conrow R E, Dean W D, Zinke P W, et al. Enantioselective Synthesis of Brinzolamide(AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The "DCAT Route" to Thiophenesulfonamides. Organic Process Research & Development,1999,3 (2):114-120.
[25]Sathe D G, Tarur R V, Bhise N B.Improved process for the preparation of (R)-(+)-4-(ethylamino)-3,4-Dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfona mide-1,1-Dioxide. WO:2008062463,2008-05-29.
[26]Catasus A M, Garcia T J. Process for the Preparation of Brinzolamide and Intermediates Thereof. WO 2 008 132 114,2008-11-06.
[27]Brown H C, Chandrasekharan J, Ramachandranlb P V. Chiral Synthesis via Organoboranes.14. Selective Reductions.41.Diisopinocampheylchloroborane, an
Exceptionally Efficient Chiral Reducing Agent. Journal of American Chemical Society, 1988,110:1539-1546.
[28]Brown H C, Jadhavl P K. Asymmetric Carbon-Carbon Bond Formation via β-Allyldiisopinocampheylborane. Simple Synthesis of Secondary Homoallylic Alcohols with Excellent Enantiomeric Purities. Journal of American Chemical Society,1983,105: 2092-2093.
[29]Mori A, Yamamoto H. Diisopinocampheylchloroborane, a Remarkably Efficient Chiral Reducing Agent for Aromatic Prochiral Ketones.The Journal of Organic Chemistry, 1985,50:5446-5448.
[30]Takahashi T, Kanda Y, Nemoto H. Highly Efficient Asymmetric Reduction of a-Tertiary Alkyl Ketones with Diisopinocampheylchloroborane.The Journal of Organic Chemistry, 1986,51:3394-3396.
[31]Midland M M,Creer S, Tramontano A, et al.Chiral Trialkylborane Reducing Agents. Preparation of 1-Deuterio Primary Alcohols of High Enantiomeric Purity. Journal of American Chemical Society,1979,101(9):2352-2355.
[32]Midland M M, Kazubski A. NB-Enantride, a New Chiral Trialkylborohydride for the Asymmetric Reduction of Ketones. The Journal of Organic Chemistry,1982,47: 2496-2498.
[33]韦莹莹,王维德,赵鹏.酮类化合物的不对称还原.化工技术与开发,2010,39(1)：17-20.
[34]王维德,王宁辉,黄颖芬.酮的不对称还原研究进展.化学工业与工程,2007,24(3)：277-282.
[35]Masutani K, Uchida T, Irie R, et al. Catalytic Asymmetric and Chemoselective Aerobic Oxidation:Kinetic Resolution of Sec-alcohols. Tetrahedron Letters,2000(41): 5119-5123.
[36]胡艾希,曾昭琼.硼氢化锌在不对称合成中的应用.化学试剂,1989,11(1)：21-25,7.
[37]Noyori R, Tomino I, Tanimoto Y, et al.Rational Designing of Efficient Chiral Reducing Agents. Highly Enantioselective Reduction of Aromatic Ketones by Binaphthol-Modified Lithium Aluminum Hydride Reagents. Journal of American Chemical Society,1984,106:6709-6716.
[38]Ohkuma T, Ooka H, Hashiguchi S, et al. Practical Enantioselective Hydrogenation of Aromatic Ketones. Journal of American Chemical Society,1995,117:2675-2616.
[39]Deloux L, Srebnik M. Asymmetric Boron-Catalyzed Reactionst. Chemical Reviews, 1993,93:763-784.
[40]Bardot V, Besse P, Miahle Y G, et al.Microbial Synthesis of (+)-(3R)-Ethyl 3-hydroxy-3-(3,4-dimethoxyphenyl)propionate. Tetrahedron:Asymmetry,1996,7(4): 1077-1088.
[41]Molinari F, Occhiato E G, Aragozzini F. Microbial Biotransformations in Water/Organic Solvent System. Enantioselective Reduction of Aromatic β-and y-nitroketones. Tetrahedron:Asymmetry,1998,9:1389-1394.
[42]Elderfield R C, Craig L C, Lauer W M, et al.A Study of Plasmochin and the Occurrence of Rearrangements in the Preparation of Certain Plasmochin Analogs. Journal of American Chemical Society,1946,68(8):1516-1523.
[43]James B, Hendrickson, Bergeron R, et al.Triflamides for Protection and Monoalkylation of Amines and a New Gabriel Synthesis.Tetrahedron Letters,1973,14(39):3839-3842.
[44]Suga K, Watanabe S,Fujita T, et al.N-Alkylation of Primary and Secondary Amines by Alkyl Halides and Lithium Naphthalene. Bulletin of the Chemical Society of Japan, 1969,42(12):3606-3608.
[45]Gibson M S, Bradshaw R W. The Gabriel Synthesis of Primary Amines.Angewandte Chemie International Edition,1968,7(12):919-930.
[46]Snieckus V. Directed Ortho Metalation. Tertiary Amide and O-Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics.Chemical Reviews,1990,90: 879-933.
[47]Shinkai I. A Practical Asymmetric Synthesis of a Novel Topically Active Carbonic Anhydrase Inhibitor. Journal of Heterocyclic Chemistry,1992,29:627-630.
[48]Jones T K, Mohan J J, Xavier L C, et al. An asymmetric synthesis of MK-0417. Observations on oxazaborolidine-catalyzed reductions. The Journal of Organic Chemistry,1991,56(2):763-769.
[49]Tsai H J, Chou S Y, Chuang S H, et al. D-420720, A Novel Orally Active Sulfonamide Compound Dipeptidyl Peptidase IV Inhibitor:Structure and Activity Relationship of Arylsulfonamide to Dipeptidyl Peptidase IV Inhibition. Drug Development Research, 2008,69:514-519.
[50]Blacklock T J, Sohar P, Butcher J W, et al. An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507:5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride. The Journal of Organic Chemistry,1993,58(7):1672-1679.
[51]DuPriest M T, Zinke P W, Conrow R E, et al. Enantioselective Synthesis of AL-4414A, a Topically Active Carbonic Anhydrase Inhibitor. The Journal of Organic Chemistry, 1997,62:9372-9375.
[52]Baker R H, Dodson R M, Riegel B.The Cleavage of Organic Sulfides with Chlorine. Journal of American Chemical Society,1946,68:2636-2639.
[53]Kwart H, Miller R K. Chlorinolysis of Su(?)(?)(?)(?)-Carbon Bonds in Aryl-Alkyl Sulfides. Journal of American Chemical Society,1956,78:5008-5011.
[54]Remuzon P, Dussy C, Jacquet J P, et al.4-Hydroxy-2-Methyl-3(2H)-Isothiazolone-1, 1-Dioxide as Protecting Group of 4-(N-Methylaminosulfonyi) methyiphenyihydrazine during Fischer Indole Synthesis. Tetrahedron Letters,1995,36(35):6227-6230.
[55]Poss M A, Reid J A. The Use of Diphenylmethyl as a Sulfonamide Protecting Group. Tetrahedron Letters,1992,33(48):7291-7292.
[56]Szymonifka M J, Heck J V. The Synthesis and Reactions of 4-Carbomethoxy β-Syntams. Tetrahedron Letters,1989,30(22):2869-2872.
[57]Heck J V, Christensen B G. Nuclear Analogs of β-Lactam Antibiotics I.The synthesis of 6β-amidocyclonocardicins. Tetrahedron Letters,1981,22(50):5027-5030.
[58]Love B, Kormendy M F. N-Sulphonylimino Esters. Canadian Journal of Chemistry, 1964,42(1):176-178.
[59]Adkins H, Burgoyne E E, Schneide H J. The Copper-Chromium Oxide Catalyst for Hydrogenation. Journal of American Chemical Society,1950,72:2626-2629.
[60]张铸勇.精细有机合成单元反应.上海：华东理工大学出版社,2003,
[61]Edwards M L, Stemerick D M, McCarthy J R. Stereospecific Synthesis of Secondary Amines by the Mitsunobu Reaction. Tetrahedron Letters,1990,31(24):3417-3420.
[62]Scozzafava A, Briganti F, Mincione G, et al. Carbonic Anhydrase Inhibitors:Synthesis of Water-Soluble, Aminoacyl/Dipeptidyl Sulfonamides Possessing Long-Lasting Intraocular Pressure-Lowering Properties via the Topical Route. Journal of Medicinal Chemistry,1999,42:3690-3700.
[63]Supurana C T, Briganti F, Menabuoni L, et al. Carbonic anhydrase inhibitors-Part 78#. Synthesis of Water-soluble Sulfonamides Incorporating β-alanyl Moieties, Possessing Long Lasting-intraocular Pressure Lowering Properties via the Topical Route. European Journal of Medicinal Chemistry,2000,35:309-321.
[64]Scozzafava A, Menabuoni L, Mincione F, et al.Carbonic Anhydrase Inhibitors: Synthesis of Sulfonamides Incorporating Dtpa Tails and of Their Zinc Complexes with Powerful Topical Antiglaucoma Properties. Bioorganic & Medicinal Chemistry Letters, 2001,11:575-582.
[65]尤启东.药物化学.北京：化学工业出版社,2004,35-38.
[66]郭宗儒.药物化学总论.第二版.北京：中国医药科技出版社,2003,474-476.
[67]Gallagher D J, Beak P.Is Halogen-Lithium Exchange Intramolecularly Competitive with Removal of an Acidic Hydrogen? Reinvestigation of a Recent Claim. Journal of American Chemical Society,1991,113:7984-7987.
[68]Snieckus V. Directed Ortho Metalation. Tertiary Amide and & Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics. Chemical Reviews,1990,90: 879-933.
[69]Campagne J M. Total Syntheses of Lysobactin(Katanosin B). Angewandte Chemie International Edition,2007,46(45):8548-8552.
[70]Von Nussbaum F, Anlauf S,Benet-Buchholz J, et al.Structure and Total Synthesis of Lysobactin (Katanosin B).Angewandte Chemie International Edition,2007,46(12): 2039-2042.