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研究生: 史南卡
Santosh Salunke
論文名稱: 1. Design and Synthesis of Histone Deacetylase Inhibitors for Lung and Breast Cancer. 2. Asymmetric Aerobic Oxidation of α-Hydroxy Acid Derivatives Catalyzed by Reusable, Polystyrene Supported Chiral N-Salicylidine Oxidovanadium tert-Leucinates.
1. Design and Synthesis of Histone Deacetylase Inhibitors for Lung and Breast Cancer. 2. Asymmetric Aerobic Oxidation of α-Hydroxy Acid Derivatives Catalyzed by Reusable, Polystyrene Supported Chiral N-Salicylidine Oxidovanadium tert-Leucinates.
指導教授: 李位仁
Lee, Way-Zen
陳建添
Chen, Chien-Tien
學位類別: 博士
Doctor
系所名稱: 化學系
Department of Chemistry
論文出版年: 2011
畢業學年度: 99
語文別: 英文
論文頁數: 256
中文關鍵詞: 組蛋白去乙醯酶抑制劑乳癌及肺癌抗癌藥物速配化學細胞成像不對稱氧化動力光學對拆離可回收手性氧釩金屬錯合物四聚體增效式的汞離子篩選
英文關鍵詞: Histone deacetylase inhibitors, Lung and Breast cancer, Anti-tumor agents, Click Chemistry, Fluorescent HDACI-QD Conjugate, Cellular Imaging, Asymmetric, Kinetic Resolution, Chiral Mandelic acid derivatives, Reusable Chiral Vanadyl complexes, Tetramers, Hg(II)-specific detection and removal
論文種類: 學術論文
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  • 我們開發出組蛋白去乙醯酶抑制劑的簡單製備方法。其中一種化合物OSU-HDAC-44,在NSCLC及異種移植具有抗腫瘤活性的效能。此化合物不只會抑制癌症細胞的生殖能力,並且在許多的NSCLC細胞株會引發細胞自毀,其效能是SAHA的三到四倍。此外其亦可藉由抑制癌細胞在生物體內的生長,而不影響到身體體重、器官及血液的狀態。另外新設計出的化合物對乳癌細胞也有抑制的活性。
    N-hydroxy p-(acylamido)benzamide (HAAC) 是組蛋白去乙醯酶抑制劑,其可藉由控制賴胺酸N-端的去乙醯反應,造成含有腫瘤抑制基因之染色體位點的染色質濃縮及轉錄失活。在HDAC抑制劑的概念設計方面,我們以速配化學合成Dendron化合物,並藉由硫酯官能基將之接合在螢光CdSe/ZnS量子點上。螢光HDACI-CdSe/ZnS結合物可抑制A549肺癌細胞的生長。此外我們也利用共軛焦顯微圖像證明出此結合物會被傳遞至肺癌細胞核內。
    在催化方面,我們將本實驗室所開發出的氧釩金屬錯合物藉由速配化學將之固定在疊氮聚苯乙烯的聚合物上(PSS),並成功將此聚苯乙烯聚合物的錯合物應用在-羥基酯類衍生物的不對稱催化空氣型氧化反應上面;且其鏡像超越值可高達99%,影響因子為41。值得一提的是此高分子類型催化劑可以藉由過濾的方式將之回收再利用。
    最後我們利用Na-鉗合的C4-對稱四聚簇狀體來進行增效式的汞離子篩選。在含有十種大小接近之金屬離子水溶液中,可選擇性地辨識出汞離子並將它篩選出來。此外,所生成的Hg2+-鉗合的C4-對稱四聚簇狀體與硫酸鈉進行離子交換後,亦可再還原成Na+-鉗合的C4-對稱四聚簇狀體,並可繼續作為汞離子的特殊篩選傳送與回收。

    We have developed short protocol for the preparation of compounds having histone deacetylase inhibition activities, as shown in chapter 1. Among these compounds, OSU-HDAC-44, displayed promising antitumor activities in non small lung cancer cell (NSCLC) and xenograft models. This compound not only repressed cell viability but also induced apoptosis in various NSCLC cell lines with 3-4 times greater potency than SAHA (known anticancer drug). In addition, submicromolar concentration of OSU-HDAC-44 exhibited prominently synergistic effects in combination with cisplatin on suppressing proliferation of NSCLC cell lines. Furthermore, it induced cell apoptosis and thereby inhibited tumor growth in vivo without adversely affected body weight, major organs and hematological parameters. Collectively, these results suggested that OSU-HDAC-44 is a promising HDAC inhibitor for NSCLC treatment. Additionally, we have also prepared two novel compounds for HDAC inhibition. Among these two molecules, one bearing tans-cyclopropyl moiety exhibited promising activities towards lung and breast cancer cells.
    N-hydroxy p-(acylamido)benzamide (HAAC) is a histone deacetylase (HDAC) inhibitor, which regulates deacetylation of the N-terminal group of lysine in histone, leading to chromatin compaction and transcriptional inactivation of chromosomal loci containing tumor suppressor genes. A new tri-antennary, N-hydroxy-p-(Acylamido) benzamide (HAAC) capped gallamide anchor with thiolate focal group is synthesized via click chemistry. The resulted highly hydrophilic dendron was efficiently anchored onto the surface of CdSe/ZnS core/shell nanoparticles in a covalent fashion, as evidenced by 1H NMR spectrum of the resultant nanohybrid with intact core fluorescent property. The water-miscible nanohybrid which bears peripheral HAAC as the HDAC inhibitor was found smoothly uptaken by lung cancer cells and translocated inside cell nucleus in 2-3 hours, as evidenced by confocal microscopic analysis. In addition, Nano-HAAC displayed promising activities towards A549 and H1299 lung cancer cell lines. Nanohybrid-HAAC at 20 nM induced cell cycle arrest at G2/M and eventually led to apoptotic cell death of lung cancer cell lines, demonstrating that nanohybrid-HAAC is much more potent in inhibiting lung cancer cell growth than parental HTPB. In addition, nanohybrid-HAAC was more effective than the parental HTPB to increase the acetylation of histone proteins and non-histone proteins. Our results provided the compelling evidences that encapsulation of quantum dots with triantennary dendritic HDAC inhibitors represent a feasible and novel strategy for drug delivery preserving the biological effects of drug.
    In chapter 3, we have documented the first successful synthesis of heterogeneous chiral vanadium complexes through direct immobilization of C5-propargyl ether modified, chiral N-Salicylidine oxidovanadium tert-leucinates onto 4-azidomethyl-substituted polystyrene by click chemistry. This protocol offers promising alternative to synthesize polymer bound catalyst which is prepared by immobilization of ligands followed by metallation. The grafting occurred cleanly, under mild conditions, affording heterogeneous chiral vanadium (V) catalysts with excellent vanadium loadings. The resulting polystyrene-supported (PSS) catalysts were then successfully used in asymmetric, aerobic oxidation of α-hydroxy carboxylic acid derivatives with excellent enantioselectivities (up to 99% ee, krel up to 41). In addition, practical scale synthesis of optically pure, mandelic acid derivatives can be made with only 3 mol% loading of PSS catalyst in CHCl3.These PSS catalysts can be readily recovered by filtration and reused for at least four consecutive runs without discernible loss of reactivity and enantioselectivity.
    In chapter 4, we have demonstrated a unique green protocol for highly sensitive and specific Hg(II) recognition and transport from an aqueous solution containing ten different M+ and M2+ of similar size by utilizing two tailor-made, C4-symmetric Na+-bound tetramers based on simple chiral oxidovanadium(V) methoxide complexes. Exclusive swapping of Na+ by Hg2+ in these tetramers can be achieved readily in reasonable time scale with discernible δ changes of their 51V signals by 5 ppm and Δε change of their CD-ORD spectra by 8-49% at 267-272 and 400-417 nm. The structural identify was subsequently confirmed by X-ray crystallographic analysis. Furthermore, the original Na+-bound cluster can be regenerated by simply treating the corresponding Hg2+ Cluster in CDCl3 with a saturated, aqueous solution of Na2SO4 in 5 min. Reusability and sustainability of the sodium clusters make the newly developed system unique and highly desirable for the Hg2+-specific recovery and storage as HgSO4. Our experimental findings offer new and tailor-made opportunity for rapid, easy, and economical diagnosis and removal of toxic metal ions from highly contaminated environmental sewage.

    Table of Contents. Acknowledgements. i Table of Contents. iii Index of Schemes. vi Index of Figures. x Index of Tables. xv Abbreviations. xvi Abstract. xix Permission letter for biological studies by Prof. Yi-Ching Wang. xxiv Chapter 1. Design and Synthesis of Histone Deacetylase Inhibitors for Lung and Breast Cancer. 1.1. Introduction and Background. 1 1.2. Results. 6 1.2.1. Synthesis and characterization of HDAC inhibitors 2, 5, 7 and 9. 6 1.2.2. Molecular Docking Assay of 2 and 5. 9 1.2.3. In vitro HDAC inhibition assay of 2, 5, 7 and 9. 10 1.2.4. In vivo HDAC inhibition assay of 2, 5 and 9. 19 1.3. Discussions. 22 1.4. Conclusion. 24 Chapter 2. Synthesis of Dendritic, Histone Deacetylase Inhibitor-QD Conjugate for Cancer Cell Imaging and Delivery. 2.1. Introduction and Background. 25 2.2. Results and Discussions. 36 2.2.1. Rational design of QD-HDAC inhibitor conjugate 30 (Nano-HAAC). 36 2.2.2. Synthesis and characterization of nanohybrid 21(Nano-galactose) and 30. 37 2.2.3. Biological evaluation of HDAC inhibitor capped nanohybrid 30. 47 2.4. Conclusion. 55 Chapter 3. Asymmetric Aerobic Oxidation of α-Hydroxy Acid Derivatives Catalyzed by Reusable, Polystyrene Supported Chiral N-Salicylidine Oxidovanadium tert-Leucinates. 3.1. Introduction and Background. 56 3.2. Results and Discussions. 69 3.2.1. Design of PS supported chiral vanadyl catalysts via click chemistry. 69 3.2.2. Synthesis and characterization of PS bound vanadyl catalysts 35 and 39. 70 3.2.3. Structural analysis of PSS catalysts 35 and 39 by PyMOL. 74 3.2.4. Evaluation of PSS catalysts 35 and 39 in asymmetric aerobic oxidation. 74 3.2.5. Recovery and Recycling of PSS catalyst 39. 82 3.2.6. Practical scale synthesis of enantioenriched benzyl mandelate. 85 3.3. Mechanistic proposal. 85 3.4. Conclusion. 88 3.5. Future plan. 89 Chapter 4. Synthesis of Sodium Vanadate-Centered Quadruples from Chiral Oxidovanandium tert-butylglycinates for Synergistic Hg2+-Specific Detection and Removal. 4.1. Introduction and Background. 91 4.2. Results and Discussions. 94 4.2.1. Chemistry. 94 4.2.2. Crystal structure of 3,5-Di-I-Hg. 99 4.2.3. Competitive binding experiments. 102 4.2.4. Recovery and recycling of Na-cluster 58-Na. 108 4.2.5. Evaluation of PS bound vanadyl clusters and their homogeneous -counterparts in the selective detection and removal of Hg2+. 110 4.2.6. Further applications of vanadyl tetramers in drug encapsulation and their delivery. 124 4.3. Conclusion. 128 Experimental Section. 130 References. 241 Appendix. 1H NMR, 13 CNMR, 51V NMR, IR, Mass and HPLC. S1

    (1) (a) Hill-Harmon, M. B.; Murray, T.; Thun, M. C. A. Cancer J. Clin. 2001, 51, 15. (b)
    Danesi, R.; de Braud, F.; Fogli, S.; de Pas, T. M.; Di Paolo, A. Pharmacol Rev. 2003, 55,
    57. (c) Yang, P.; Allen, M. S.; Aubry, M. C.; Wampfler, J. A.; Marks, R. S. Chest. 2005,
    128, 452.
    (2) (a) Socinski, M. A. Clin. Cancer Res. 2004, 10, 4210s. (b) Pfister, D. G.; Johnson, D.
    H.; Azzoli, C. G.; Sause, W.; Smith T. J. J. Clin. Oncol. 2004, 22, 330. (c) Stinchcombe,
    T. E.; Socinski, M. A. Proc. Am. Thorac. Soc. 2009, 6, 233.
    (3) (a) Sandler, A.; Gray, R.; Perry, M. C.; Brahmer, J.; Schiller J. H. N. Engl. J. Med.
    2006, 355, 2542. (b) Shepherd, F. A.; Rodrigues, P. J.; Ciuleanu, T.; Tan, E. H.; Hirsh, V.
    N. Engl. J. Med. 2005, 353, 123.
    (4) (a) Jones, P. A.; Baylin, S. B. Cell 2007, 128, 683. (b) Bhalla, K. N. J. Clin. Oncol.
    2005, 23, 3971. (c) Barlesi, F.; Giaccone, G.; Gallegos-Ruiz, M. I.; Loundou, A.; Span, S.
    W. J. Clin. Oncol. 2007, 25, 4358.
    (5) Tanner, K. G.; Trievel, R. C.; Kuo, M. H. J. Biol. Chem. 1999, 274, 18157.
    (6) Gregory, P. D.; Wagner, K.; Horz, W. Exp. Cell Res. 2001, 265, 195.
    (7) Roth, S. Y.; Denu, J. M.; Allis, C. D. Annu. Rev. Biochem. 2001, 70, 81.
    (8) Minucci, S; Pelicci, P.G. Nat. Rev. Cancer 2006, 6, 38.
    (9) (a) Johnstone, R. W. Nat. Rev. Drug Discov. 2002, 1, 287. (b) Xu, W. S.; Parmigiani,
    R. B.; Marks, P. A. Oncogene 2007, 26, 5541.
    242
    (10) (a) Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Nat. Rev. Drug Discov. 2006, 5, 769.
    (b) Dokmanovic, M.; Marks, P. A. J. Cell. Biochem. 2005, 96, 293. (c) Miller, T. A.;
    Witter, D. J.; Belvedere, S. J. Med. Chem. 2003, 46, 5097. (d) Rasheed, W. K.; Johnstone,
    R. W.; Prince, H. M. Expert Opin. Investig. Drugs 2007, 16, 659.
    (11) Yoshida, M.; Kijima, M.; Akita, M.; Beppu, T. J. Biol. Chem. 1990, 265, 17174.
    (12) Marsoni, S.; Damia, G.; Camboni, G. Epigenetics 2008, 3, 164.
    (13) Mann, B. S.; Johnson, J. R.; Cohen, M. H.; Justice, R.; Pazdur, R. Oncologist 2007,
    12, 1247.
    (14) Finnin, M. S.; Donigian, J. R.; Cohen, A.; Richon, V. M.; Rifkind, R. A.; Marks, P.
    A.; Breslow, R.; Pavletich, N. P. Nature 1999, 401, 188.
    (15) (a) Vannini, A.; Volpari, C.; Filocamo, G.; Caroli Casavola, E.; Brunetti, M.;
    Renzoni, D.; Chakravarty, P.; Paolini, C.; De Francesco, R.; Gallinari, P.; Steinkuhler, C.;
    Di Marco, S. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 15064. (b) Somoza, J. R.; Skene, R.
    J.; Katz, B. A.; Mol, C.; Ho, J. D.; Jennings, A. J.; Luong, C.; Arvai, A.; Buggy, J. J.; Chi,
    E.; Tang, J.; Sang, B.-C.; Verner, E.; Wynands, R.; Leahy, E. M.; Dougan, D. R.; Snell,
    G.; Navre, M.; Knuth, M. W.; McRee, D. E.; Tari, L. W. Structure 2004, 12, 1325.
    (16) (a) Lu, Q.; Yang, Y.-T.; Chen, C.-S.; Davis, M.; Byrd, J. C.; Etherton, M. R.; Umar,
    A.; Chen, C. -S. J. Med. Chem. 2004, 47, 467. (b) Lu, Q.; Wang, D. -S.; Chen, C. -S.; Hu,
    Y. -D.; Chen, C. -S. J. Med. Chem. 2005, 48, 5530.
    (17) (a) Shieh, J. M.; Wei, T. T.; Tang, Y. A.; Huang, S. M.; Wen, W. L.; Chen, M. Y.;
    Salunke, S. B.; Chen, C. -T.; Chen, C. -S.; Wang, Y. -C. PLoS ONE 2011, in revision. (b)
    Tang, Y. A.; Wen, W. L.; Chang, J. W.; Wei, T. T.; Tan, Y. H. C.; Salunke, S.; Chen, C. -
    T.; Chen, C. -S.; Wang, Y. -C. PLoS ONE 2010, 5, E12417.
    243
    (18) (a) Lens, S. M.; Vader, G.; Medema, R. H. Curr. Opin. Cell. Biol. 2006, 18, 616. (b)
    Carmena, M.; Earnshaw, W. C. Nat. Rev. Mol. Cell. Biol. 2003, 4, 842.
    (19) (a) Richon, V. M.; Sandhoff, T. W.; Rifkind, R. A.; Marks, P. A. Proc. Natl. Acad.
    Sci. U. S. A. 2000, 97, 10014. (b) Gui, C. Y.; Ngo, L.; Xu, W. S.; Richon, V. M.; Marks,
    P. A. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 1241.
    (20) (a) Canes, D.; Chiang, G. J.; Billmeyer, B. R.; Austin, C. A.; Kosakowski, M. Int. J.
    Cancer 2005, 113, 841. (b) Vigushin, D. M.; Ali, S.; Pace, P. E.; Mirsaidi, N. Ito, K. Clin.
    Cancer Res. 2001, 7, 971.
    (21) Glotzer, M. Science 2005, 307, 1735.
    (22) Vischioni, B.; Oudejans, J. J.; Vos, W.; Rodriguez, J. A.; Giaccone, G. Mol. Cancer
    Ther. 2006, 5, 2905.
    (23) (a) Glaser, K. B.; Staver, M. J.; Waring, J. F.; Stender J.; Ulrich, R. G. Mol. Cancer
    Ther. 2003, 2, 151. (b) Mitsiades, C. S.; Mitsiades, N. S.; McMullan, C. J.; Poulaki, V.;
    Shringarpure, R. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 540. (c) Peart, M. J.; Smyth, G.
    K.; van Laar, R. K.; Bowtell, D. D.; Richon, V. M. Proc. Natl. Acad. Sci. U. S. A. 2005,
    102, 3697.
    (24) (a) Li, J.; Lin, Q.; Wang, W.; Wade, P.; Wong, J. Genes Dev. 2002, 16, 687. (b)
    Wilson, A. J.; Chueh, A. C.; Togel, L.; Corner, G. A.; Ahmed, N. Cancer Res. 2010, 70,
    609.
    (25) (a) Jr. Bruchez, M.; Moronne, M.; Gin, P.; Weiss, S.; Alivisatos, A. P. Science 1998,
    281, 2013. (b) Anikeeva, N.; Lebedeva, T.; Clapp, A. R.; Goldman, E. R.; Dustin, M.
    L.; Mattoussi, H.; Sykulev, Y. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16846. (c)
    244
    Michalet, X.; Pinaud, F. F.; Bentolila, L. A.; Tsay, J. M.; Doose, S.; Li, J. J.; Sundaresan,
    G.; Wu, A. M.; Gambhir, S. S.; Weiss, S. Science 2005, 307, 538.
    (26) (a) Zimmer, J. P.; Kim, S.-W.; Ohnishi, S.; Tanaka, E.; Frangioni, J. V.; Bawendi,
    M. G. J. Am. Chem. Soc. 2006, 128, 2526. (b) So, M. -K.; Xu, C.; Loening, A. M.;
    Gambhir, S. S.; Rao, J. Nat. Biotechnol. 2006, 24, 339.
    (27) (a) Somers, R. C.; Bawendi, M. G.; Nocera, D. G. Chem. Soc. Rev. 2007, 36, 579.
    (b) Medintz, I. L.; Clapp, A. R.; Brunel, F. M.; Tiefenbrunn, T.; Tetsuo, U. H.; Chang, E.
    L.; Deschamps, J. R.; Dawson, P. E.; Mattoussi, H. Nat. Mater. 2006, 5, 581. (c) Zhang,
    C. Y.; Yeh, H. C.; Kuroki, M. T.; Wang, T. H. Nat. Mater. 2005, 4, 826.
    (28) (a) Parak, W. J.; Pellegrino, T.; Plank, C. Nanotechnology 2005, 16, R9. (b)
    Mitchell, G. P.; Mirkin, C.A.; Letsinger, R. L. J. Am. Chem. Soc. 1999, 121, 8122. (c)
    Wang, Y. A.; Li, J. J.; Chen, H.; Peng, X. J. Am. Chem. Soc. 2002, 124, 2293. (d) Gao,
    X.; Yang, L.; Petros, J. A.; Marshall, F. F.; Simons, J. W.; Nie, S. Curr.Opin.Biotechnol.
    2005, 16, 63.
    (29) (a) Chan, W. C. W.; Nie, S. Science 1998, 281, 2016. (b) Wang, Q. B.; Xu, Y.;
    Zhao, X. H.; Chang, Y.; Liu, Y.; Jiang, L. J.; Sharma, J.; Seo, D. -K.; Yan, H. J. Am.
    Chem. Soc. 2007, 129, 6380.
    (30) (a) Zhang, C.-Y.; Yeh, H.-C.; Kuroki, M. T.; Wang, T. -H. Nat. Mater. 2005, 4, 826.
    (b) Medintz, I. L.; Tetsuouyeda, H.; Goldman, E. R.; Mattoussi, H. Nat. Mater. 2005, 4,
    435.
    245
    (31) (a) Gill, R.; Willner, I.; Shweky, I.; Banin, U. J. Phys. Chem. B. 2005, 109, 23715.
    (b) Pinaud, F.; King, D.; Moore, H.-P.; Weiss, S. J. Am. Chem. Soc. 2004, 126, 6115.
    (32) (a) Chen, A. A.; Derfus, A. M.; Khetani, S. R.; Bhatia, S. N. Nucleic Acids Res.
    2005, 33, e190. (b) Tan, W. B.; Jiang, S.; Zhang, Y. Biomaterials 2007, 28, 1565.
    (33) Bagalkot, V.; Zhang, L.; Levy-Nissenbaum, E.; Jon, S.; Kantoff, P. W.; Langer, R.;
    Farokhzad, O. C. Nano Lett. 2007, 7, 3065.
    (34) Weng, K. C.; Noble, C. O.; Papahadjopoulos-Sternberg, B.; Chen, F. F.;
    Drummond, D. C.; Kirpotin, D. B.; Wang, D.; Hom, Y. K.; Hann, B.; Park, J. W. Nano
    Lett. 2008, 8, 2851.
    (35) Rosenthal, S. J.; Tomlinson, I.; Adkins, E. M.; Schroeter, S.; Adams, S.; Swafford,
    L.; McBride, J.; Wang, Y.; DeFelice, L. J.; Blakely, R. D. J. Am. Chem. Soc. 2002, 124,
    4586.
    (36) Gussin, H. A.; Tomlinson, I.; Little, D. M.; Warnement, M. R.; Qian, H.; Rosenthal,
    S. J.; Pepperberg, D. R. J. Am. Chem. Soc. 2006, 128, 15701.
    (37) Clarke, S. J.; Hollmann, C. A.; Zhang, Z.; Suffern, D.; Bradforth, S. E.; Dimitrijevic,
    N.; Minaric, W. G.; Nadeau, J. L. Nat. Mater. 2006, 5, 409.
    (38) Byrne, S. J.; le Bon, B.; Corr, S. A.; Stefanko, M.; O’Connor, C.; Gun’ko, Y. K.;
    Rakovich, Y. P.; Donegan, J. F.; Williams, Y.; Volkov, Y.; Evans, P. ChemMedChem
    2007, 2, 183.
    (39) Narayanan, S. S.; Sinha, S. S.; Pal, S. K. J. Phys. Chem. C. 2008, 112, 12716.
    246
    (40) Chen, C.-T.; Pawar, V. D.; Munot, Y. S.; Chen, C.-C.; Hsu, C.-J. Chem.Commun.
    2005, 19, 2483.
    (41) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem.
    Int. Ed. 2002, 41, 2596. (b) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
    2002, 67, 3057. (c) Wang, Q.; Chan, T. R.; Hilgraf, R.; Fokin, V. V.; Sharpless, K. B.;
    Finn, M. G. J. Am. Chem. Soc. 2003, 125, 3192. (d) Kolb, H. C.; Sharpless, K. B. Drug
    Discovery Today 2003, 8, 1128.
    (42) Chen, C.-T.; Munot, Y. S.; Salunke, S. B.; Wang, Y.-C.; Lin, R.-K.; Lin, C.-C.;
    Chen, C.-C.; Liu, Y. -H. Adv. Func. Mat. 2008, 18, 527.
    (43) (a) Marks, P.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K.
    Nat. Rev. Cancer 2001, 1, 194. (b) Hassig, C. A.; Schreiber, S. L. Curr. Opin. Chem.
    Biol. 1997, 1, 300.
    (44) Witt, O.; Deubzer, H. E.; Milde, T.; Oehme, I. Cancer Lett. 2009, 277, 8.
    (45) Ungerstedt, J. S.; Sowa, Y.; Xu, W. S.; Shao, Y.; Dokmanovic, M.; Perez, G.; Ngo,
    L.; Holmgren, A.; Jiang, X.; Marks, P. A. Proc. Natl. Acad. Sci.U.S.A. 2005, 102, 673.
    (46) (a) Grunstein, M. Nature 1997, 389, 349. (b) Hebbes, T. R.; Thorne, W.; Crane-
    Robinson, A.; EMBO C. J. 1988, 7, 1395. (c) Tazi, J.; Bird, A. Cell 1990, 60, 909.
    (47) (a) Jung, M. Curr. Med. Chem. 2001, 8, 1505. (b) Kramer, O. H.; Gottlicher, M.;
    Heinzel, T. Trends Endocrinol. Metab. 2001, 12, 294. (c) Marks, P. A.; Richon, V. M.;
    Rifkind, R. A. J. Natl. Cancer Inst. 2000, 92, 1210.
    (48) Paris, M.; Porcelloni, M.; Binaschi, M.; Fattori, D. J. Med.Chem. 2008, 51, 1505.
    247
    (49) Grant, S.; Easley, C.; Kirkpatrick, P. Nat. Rev. Drug Discov. 2007, 6, 21.
    (50) (a) Chen, Y.; Sanchez, M. L.; Savoy, D. N.; Billadeau, D. D.; Dow, G. S.;
    Kozikowski, A. P. J. Med.Chem. 2008, 51, 3437.
    (51) Pirali, T.; Pagliai, F.; Mercurio, C.; Boggio, R.; Canonico, P. L.; Sorba, G.; Tron, G.
    C.; Genazzani, A. A. J. Comb. Chem. 2008, 10, 624.
    (52) Chen, P. C.; Patil, V.; Guerrant, W.; Green, P.; Oyelere, A. K. Bioorg. Med. Chem.
    2008, 16, 4839.
    (53) Shen, J.; Woodward, R.; Kedenburg, P. J.; Liu, X.; Chen, M.; Fang, L.; Sun, D.;
    Wang, P. G. J. Med.Chem. 2008, 51, 7417.
    (54) Suzuki, T.; Ota, Y.; Kasuya, Y.; Mutsuga, M.; Kawamura, Y.; Tsumoto, H.;
    Nakagawa, H.; Finn M. G.; Miyata, N. Angew. Chem. Int. Ed. 2010, 49, 6817.
    (55) Oyelere, A. K.; Chen, P. C.; Guerrant, W.; Mwakwari, S. C.; Hood, R.; Zhang, Y.;
    Fan, Y. J. Med. Chem. 2009, 52, 456.
    (56) Mazitschek, R.; Patel, V.; Wirth, D. F.; Clardy, J. Bioorg. Med. Chem. Lett. 2008, 18,
    2809.
    (57) Canzoneri, J. C.; Chen, P. C.; Oyelere, A. K. Bioorg. Med. Chem. Lett. 2009, 19,
    6588.
    (58) (a) Neilands, J. B. HJ. Am. Chem. SocH. 1952, 74, 4846. (b) Neilands, J. B. HJ. Biol.
    Chem.H 1995, 270, 26723. (c) Miller, M. J. Chem Rev. 1989, 89, 1563. (d) Raymond, K.
    N. Pure & Appl. Chem. 1994, 66, 773.
    (59) Miethke, M.; Marahiel, M. Microbiol. Mol. Bio. Reviews 2007, 71, 413.
    248
    (60) Ferguson, A. D.; Hofmann, E.; Coulton, J. W.; Diederichs, K.; Welte, W. Science
    1998, 282, 2215.
    (61) For reviews on transition metal catalyzed aerobic oxidations, see: (a) Wills, M.
    Angew.Chem.Int.Ed. 2008, 47, 4264. (b) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006,
    62, 8227. (c) Stoltz, B. M. Chem.Lett. 2004, 33, 362. (d) Sigman, M. S.; Jensen, D. R.
    Acc. Chem. Res. 2006, 39, 221
    (62) Vedejs, E.; Jure, M. Angew. Chem. Int. Ed. 2005, 44, 3974.
    (63) Rychnovsky, S. D.; McLernon, T. L.; Rajapakse, H. J. Org. Chem. 1996, 61, 1194.
    (64) (a) Ebner, D. C.; Trend, R. M.; Genet, C.; McGrath, M. J.; O’Brien, P.; Stoltz, B.
    M. Angew. Chem. Int. Ed. 2008, 47, 6367. (b) Krishnan, S.; Bagdanoff, J. T.; Ebner, D.
    C.; Ramtohul, Y. K.; Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2008, 130, 13475.
    (c) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2001, 123, 7725.
    (65) Jensen, D. R.; Puglsey, J. S.; Sigman, M. S. J. Am. Chem. Soc. 2001, 123, 7475.
    (66) Arita, S.; Koike, T.; Kayaki, Y.; Ikariya, T. Angew. Chem. Int. Ed. 2008, 47, 2447.
    (67) (a) Coppola, G. M.; Schuster, H. F. R-Hydroxy Acids in Enantioselective Synthesis;
    VCH: Weinheim, 1997. (b) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2005, 127,
    1080. (c) Budavari, S. The Merck Index (Merck & Co., Rahway, NJ), 11th Ed., ed. 1989,
    898. (d) Furlemmeier, A.; Quitt, P.; Vogler, K.; Lanz, P. U. S. Patent 3, 957, 758, 1976.
    (e) Mill, J.; Schmiegel, K. K.; Sha, W. N. U. S. Patent, 4, 391, 826, 1983. (f) A. Bousquet,
    A. Musolino, PCT Intl. Appl. WO 9, 918, 110, 1999. (g) Zhu, S.-F.; Cai, Y.; Mao, H.-X.;
    Xie, J.-H.; Zhou, Q.-L.; Nat.Chem. 2010, 2, 546. (h) Landwehr, M.; Hochrein, L.; Otey,
    249
    C. R.; Kasrayan, A.; Bäckvall, J.-E.; Arnold, F. H. J. Am. Chem. Soc. 2006, 128, 6058. (i)
    Del Valle, J. R.; Hanessian, S. Angew. Chem. Int. Ed. 2008, 47, 1202. (j) Diethelm, S.;
    Schindler, C. S.; Carreira, E. M. Org. Lett. 2010, 12, 3950.
    (68) For reviews on vanadium catalyzed reactions, see: (a) Hirao, T. Chem. Rev. 1997,
    97, 2707. (b) Bolm, C. Coord. Chem. Rev. 2003, 237, 245.
    (69) (a) Weng, S.-S.; Lin, Y.-D.; Chen, C.-T. Org. Lett. 2006, 8, 5633. (b) Chen, C.-T.;
    Weng, S.-S.; Kao, J.-Q.; Lin, C.-C.; Jan, M.-D. Org. Lett. 2005, 7, 3343. (c) Chen, C.-T.;
    Kuo, J.-H.; Ku, C.-H.; Weng, S.-S.; Liu, C.-Y. J. Org. Chem. 2005, 70, 1328. (d) Chen,
    C.-T.; Munot, Y. S. J. Org.Chem. 2005, 70, 8625. (e) Chen, C.-T.; Kuo, J.-H.; Pawar, V.
    D.; Munot, Y. S.; Weng, S.-S.; Ku, C.-H.; Liu, C.-Y. J. Org. Chem. 2005, 70, 1188. (f)
    Liu, C.-Y.; Pawar, V. D.; Kao, J.-Q.; Chen, C.-T. Adv. Synth. & catal. 2010, 352, 188.
    (70) Weng, S.-S.; Shen, M.-W.; Kao, J.-Q.; Munot, Y. S.; Chen, C.-T. Proc.Natl. Acad.
    Sci. U.S.A. 2006, 103, 3522.
    (71) Radosevich, A. T.; Musich, C.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 1090.
    (72) Radosevich, A. T.; Chan, V. S.; Shih, H.-W.; Toste, F. D. Angew. Chem. Int. Ed.
    2008, 47, 3755.
    (73) Pawar, V. D.; Weng, S.-S.; Bettigeri, S.; Kao, J.-Q.; Chen, C.-T. J. Am. Chem. Soc.
    2006, 128, 6308.
    (74) Chen, C.-T.; Bettigeri, S.; Weng, S.-S.; Pawar, V. D.; Lin, Y.-H.; Liu, C.-Y.; Lee,
    W.-Z. J. Org. Chem. 2007, 72, 8175.
    (75) Chen, C.-T.; Kao, J.-Q.; Salunke, S. B.; Lin, Y.-H. Org. Lett. 2011, 13, 26.
    250
    (76) Drago, C.; Caggiano, L.; Jackson, R. F. W. Angew. Chem. Int. Ed. 2005, 44, 7221.
    (77) Bolm, C.; Bienewald, F. Angew. Chem. Int. Ed. 1995, 107, 2883.
    (78) Hon, S.-W.; Li, C.-H.; Kuo, J.-H.; Barhate, N. B.; Liu, Y.-H.; Wang, Y.; Chen, C.-T.
    Org. Lett. 2001, 3, 869.
    (79) Barhate, N. B.; Chen, C.-T. Org. Lett. 2002, 4, 2529.
    (80) (a) Guo, Q. -X.; Wu, Z. -J.; Luo, Z. -B.; Liu, Q. -Z.; Ye, J. -L.; Luo, S. -W.; Cun, L.
    -F.; Gong L. -Z. J. Am. Chem. Soc. 2007, 129, 13927. (b) Takizawa, S.; Katayama, T.;
    Kameyama, C.; Onitsuka, K.; Suzuki, T.; Yanagida, T.; Kawai, T.; Sasai, H. Chem.
    Commun. 2008, 1810.
    (81) Chen, C.-T.; Lin, J.-S.; Kuo, J.-H.; Weng, S.-S.; Cuo, T.-S.; Lin, Y.-W.; Cheng, C.-
    C.; Huang, Y.-C.; Yu, J.-K.; Chou, P.-T. Org. Lett. 2004, 6, 4471.
    (82) Chen C.-T.; Lin Y.-H.; Kuo, T.-S. J. Am. Chem. Soc. 2008, 130, 12843.
    (83) For reviews on asymmetric heterogeneous catalysis, see: (a) Trindade, A. F.; Gois
    Pedro, M. P.; Afonso Carlos, A. M. Chem.Rev. 2009, 109, 418. (b) Ding, K.; Uozumi, Y.
    Handbook of Asymmetric Heterogeneous Catalysis, Wiley-VCH, Weinheim, 2008. (c)
    Heitbaum, M.; Glorius, F.; Escher, I. Angew. Chem., Int. Ed. 2006, 45, 4732 and
    references therein.
    (84) Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 4147.
    (85) Ohkuma, T.; Takeno, H.; Honda, Y.; Noyori, R. Adv. Synth. Catal. 2001, 343, 369.
    (86) Annuziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Pittilo, M. J. Org. Chem. 2001,
    66, 3160.
    251
    (87) Baleizão, C.; Gigante, B.; Garcia, H.; Corma, A. Tetrahedron 2004, 60, 10461.
    (88) Barbarini, A.; Maggi, R.; Muratori, M.; Sartori, G.; Sartorio, R. Tetrahedron Asym.
    2004, 15, 2467.
    (89) Shiels, R. A.; Venkatasubbaiah, K.; Jones, C. W. Adv.Synth.Catal. 2008, 350, 2823.
    (90) Huisgen, R. Pure Appl. Chem. 1989, 61, 613.
    (91) For further examples of catalyst immobilizaton via azide-alkyne cycloaddition, see
    (a) Wang, X. Y.; Kimyonok, A.; Weck, M. Chem. Commun. 2006, 3933. (b) Gissibl, A.;
    Finn, M. G.; Reiser, O. Org. Lett .2005, 7, 2325. (c) Mager, I.; Zeitler, K. Org. Lett.
    2010, 12, 1480. (d) Gheorghe, A.; Matsuno, A.; Reiser, O. Adv. Synth. Catal. 2006, 348,
    1016.
    (92) Bastero, A.; Font, D.; Pericàs, M. A. J. Org. Chem. 2007, 72, 2460.
    (93) Alza, E.; Cambeiro, X. C.; Jimeno, C.; Pericàs, M. A. Org. Lett. 2007, 9, 3717.
    (94) Tilliet, M.; Lundgren, S.; Moberg, C.; Levacher, V. Adv. Synth. Catal. 2007, 349,
    2079.
    (95) Schätz, A.; Haquer, M.; Reiser, O. Adv. Funct. Mater. 2009, 19, 2109.
    (96) For binding energies of V(V) species, see: Sawatzky, G.A.; Post, D. Phys. Rev. B.
    1979, 20, 1546.
    (97) (a) Renzoni, A.; Zino, F.; Franchi, E. EnViron. Res. 1998, 77, 68. (b) Benoit, J. M.;
    Fitzgerald, W. F.; Damman, A. W. EnViron. Res. 1998, 78, 118.
    252
    (98) (a) Malm, O. EnViron. Res. 1998, 77, 73. (b) Von Burg, R.; Greenwood, R. M. E.
    Merian ed.;VCH, Weinheim, 1991, 1045.
    (99) (a) Harris, H. H.; Pickering, I. J.; George, G. N. Science 2003, 301, 1203. (b)
    Boening, D. W. Chemosphere 2000, 40, 1335.
    (100) Butler, O. T.; Cook, J. M.; Harrington, C. F.; Hill, S. J.; Rieuwerts, J.; Miles, D. L.
    J. Anal. At.Spectrom. 2006, 21, 217.
    (101) Li, Y.; Chen, C.; Li, B.; Sun, J.; Wang, J.; Gao, Y.; Zhao, Y.; Chai, Z. J. Anal. At.
    Spectrom. 2006, 21, 94.
    (102) Leermakers, M.; Baeyens, W.; Quevauviller, P.; Horvat, M. Trends Anal. Chem.
    2005, 24, 383.
    (103) For reviews see: (a) Nolan, E. M.; Lippard, S. J. Chem. Rev. 2008, 108, 3443. (b)
    Domaille, D.W.; Que, E. L.; Chang, C.J. Nat. Chem. Biol. 2008, 4, 168.
    (104) Hollenstein, M.; Hipolito, C.; Larn, C.; Dietrich, D.; Perrin, D. M. Angew.Chem.,
    Int. Ed. 2008, 47, 4346.
    (105) Liu, X.; Tang, Y.; Wang, L.; Zhang, J.; Song, S.; Fan, C.; Wang, S. Adv. Mater.
    2007, 19,1471.
    (106) Ono, A.; Togashi, H. Angew. Chem. Int. Ed. 2004, 43, 4300.
    (107) Wegner, S. V.; Okesli, A.; Chen, P.; He, C. J. Am. Chem. Soc. 2007, 129, 3474.
    (108) Lee, J.-S.; Han, M. S.; Mirkin, C. A. Angew. Chem. Int. Ed. 2007, 46, 4093.
    (109) (a) Brown, N. L.; Shih, Y.-C.; Leang, C.; Glendinning, K. J.; Hobman, J. L.;
    Wilson J. R. Biochem. Soc. Trans. 2002, 30, 715. (b) Moore M. J.; Distefano, M. D.;
    Zydowsky, L. D.; Cummigs, R. T.: Walsh, C. T. Acc. Chem. Res. 1990, 23, 301.
    (110) Ersoz, M. Adv. Colloid Interface Sci. 2007, 134-135, 96.
    253
    (111) Shokrollahi, A.; Ghaedi, M.; Shamsipur, M. Quim. Nova. 2009, 32, 153.
    (112) Jabbari, A.; Esmaeili, M.; Shamsipur, M. Sep. Purif. Technol. 2001, 24, 139.
    (113) For reviews, see: (a) Davis, J. T. Angew. Chem., Int. Ed. 2004, 43, 668. (b) Davis, J.
    T.; Spada, G. P. Chem. Soc. Rev. 2007, 36, 296.
    (114) van Leeuwen, F. W. B.; Shi, X.; Davis, J. T.; Verboom, W.; Reinhoudt, D. N. J.
    Am. Chem.Soc. 2004, 126, 16575
    (115) Gouaux, E.; MacKinnon, R. Science 2005, 310, 1461.
    (116) For a biological system exhibiting C4-Symmetry : Orlova, E. V.; Rahman, M. A.;
    Gowen, B.; Volynski, K. E.; Ashton, A. C.; Manser, C.; van Heel, M.; Ushkaryov, Y. A.;
    Nature struc. Biol. 2000, 7, 48.
    (117) The negative Cotton effect at 1615 cm-1 is overlapped by the positive Cotton effect
    at 1620 cm-1. (b) For a unique reversal of couplet chirality in VCD upon chelation of bile
    pigments by Zn2+, see: Goncharova, I.; Urbanová, M. Anal. Biochem. 2009, 392, 28. (c)
    For a representative use of VCD for studying supramolecular entities, see: Setnička, V.;
    Urbanová, M.; Volka, K.; Nampally, S.; Lehn, J.-M. Chem. Eur. J. 2006, 12, 8735.
    (118) For trigonal prismatic geometry of Hg(II) complexes by multidentate amine type
    ligands, see: (a) Nolan, E. M.; Lippard, S. J. J. Am. Chem. Soc. 2007, 129, 5910. (b) Choi,
    K. S.; Kang, D.; Lee, J.-E.; Seo, J.; Lee, S. S. Bull. Korean Chem. Soc. 2006, 27,747. (c)
    Bygott, A. M. T.; Geue, R. J.; Ralph, S. F.; Sargeson, A. M.; Willis, A. C. DaltonTrans.,
    2007, 4778. (d) Huang, L.; Peng, Y.; Li, Z.; Wei, Z.; Hughes, D. L.; Zeng, X.; Luo, Q.;
    Liu, X. Inorg. Chim. Acta 2010, 363, 2664.
    (119) Salunke, S. B.; Seshubabu, N.; Chen, C. T. Adv. Synth. Catal. 2011, 353, 1234.
    254
    (120) Cheng, H.; Cao, X.; Xian, M.; Fang, L.; Cai, T. B.; Ji, J. J.; Tunac, J. B.; Sun, D.;
    Wang, P. G. J. Med.Chem. 2005, 48, 645.
    (121) Page, D.; Aravind, S.; Roy, R. J. Chem. Soc. Chem. Commun. 1996, 16, 1913.
    (122) Boden, P.; Eden, J. M.; Hodgson, J.; Horwell, D. C.; Hughes, J.; McKnight, A.T.;
    Lewthwaite, R. A. ; Pritchard, M. C.; Raphy, J.; Meecham, K.; Ratcliffe, G. S.; Chauhan,
    N. S.; Woodruff, G. N. J. Med. Chem. 1996, 39, 1664.
    (123) Deiters, A.; Cropp, T. A.; Mukherji, M.; Chin, J. W.; Anderson, J. C.; Schultz, P.
    G. J. Am. Chem. Soc. 2003, 125, 11782.
    (124) Salunke, S. B.; Tang, Y. A.; Wang, Y. C.; Chen, C. T. manuscript to be submitted
    2011.
    (125) (a) Gheorghe, A.; Matsuno, A.; Reiser, O. Adv. Synth. Catal. 2006, 348, 1016. (b)
    Arseniyadis, S.; Wagner, A.; Mioskowski, C. Tetrahedron Lett. 2002, 43, 9717.
    (126) Loaiza, P. R.; Löber, S.; Hübner H.; Gmeiner, P. Bioorg. Med. Chem. 2009, 17,
    5482.
    (127) Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 1939.
    (128) (a) Font, D.; Pericàs, M. A. J. Org. Chem. 2007, 72, 2460. (b) Tilliet, M.; Lundgren,
    S.; Moberg, C.; Levachera, V. Adv. Synth. Catal. 2007, 349, 2079. (c) Font, D.; Jimeno,
    C.; Pericàs, M. A. Org. Lett. 2006, 8, 4653.
    (129) Hajji, C.; Roller, S.; Beigi, M.; Liese, A.; Haag, R. Adv. Synth. Catal. 2006, 348,
    1760.
    255
    (130) Zhao, S.; Zhao, J.; Zhao, D. Carbohydr. Res. 2007, 342, 254.
    (131) Gharpure, S. J.; Shukla, M. K.; Vijayasree, U. Org. Lett. 2010, 70, 8625.
    (132) Basavaiah, D.; Krishna, P. R. Tetrahedron 1995, 51, 2403.
    (133) Hall, S. S.; Doweyko, L. M.; Doweyko, A. M.; Zilenovski, J. S. R. J. Med. Chem.
    1977, 20, 1239.
    (134) Blay, G.; Fernàndez, I.; Hernàndez-Olmos,V.; Marco-Aleixandre, A.; Pedro, J. R.
    Tet. Asymm. 2005, 16, 1953.
    (135) (a) Jia, Y.-X.; Katayev, D.; Kündig, E. P. Chem. Commun. 2010, 46, 130. (b) Zhou,
    N.; Polozov, A. M.; O’Connell, M.; Burgeson, J.; Yu, P.; Zeller, W.; Zhang, J.; Onua, E.;
    Ramirez, J.; Palsdottir, G. A.; Halldorsdottir, G. V.; Andresson, T.; Kiselyov, A. S.;
    Gurney, M.; Singh, J. Bioorg. Med. Chem. Lett. 2010, 20, 2658.
    (136) Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2003, 125, 7825.
    (137) Chen, C. -T.; Salunke, S. B.; Lin, Y. H.; Kuo, T. S. manuscript to be submitted
    2011.
    (138) Kleineweischede, R.; Hackenberger, C. P. R. Angew. Chem. Int. Ed. 2008, 47, 5984.
    (139) (a) Livingston, P. O.; Koganty, R.; Longenecker, B. M.; Lloyd, K. O.; Calves, M.
    Vaccine Res. 1992, 1, 99. (b) Bray, J.; Leumieux, R. U.; McPherson, T. A. J. Immunol.
    1981, 126, 1966. (c) Kichler, A.; Schuber, F. Glycoconjugate J. 1995, 12, 275. (d) Hung,
    P. Y. S.; Madej, M.; Koganty, R. R.; Longenecker, B. M. Cancer Res. 1990,50, 4308.
    256
    (140) (a) Donovan, R. S.; Datti, A.; Baek, M. G.; Wu, Q. Q.; Sas, I. J.; Korczak, B.;
    Berger, E. G.; Roy, R.; Dennis, J. W. Glycoconjugate J. 1999, 16, 607. (b) Baek, M.-G.;
    Roy, R. Biomacromolecules 2000, 1, 768.
    (141) Gabius, H.-J.; Schroter, C.; Gabius, S.; Brink, U.; Tietze, L.-F. J. Histochem.
    Cytochem. 1990, 38, 1625.
    (142) (a) Wilson, E. Chem. Eng. News 2005, 83, 128; (b) Cahnmann, H. J.; Funakoshi, K.
    Biochemistry 1970, 9, 90.

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