淡江大學覺生紀念圖書館 (TKU Library)
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系統識別號 U0002-0907201311160200
中文論文名稱 含硼一級胺類化合物之合成及其應用
英文論文名稱 Synthesis of Boron-containing Primary Amines and Their Applications
校院名稱 淡江大學
系所名稱(中) 化學學系碩士班
系所名稱(英) Department of Chemistry
學年度 101
學期 2
出版年 102
研究生中文姓名 鍾勝烜
研究生英文姓名 Sheng-Hsuan Chung
學號 600180060
學位類別 碩士
語文別 中文
口試日期 2013-06-21
論文頁數 168頁
口試委員 指導教授-潘伯申
委員-黃俊誠
委員-魏屹
中文關鍵字   peptoid  一級胺  Ugi-4CR  Suzuki reaction  Gabriel reaction 
英文關鍵字 boron  peptoid  primary amine  Ugi-4CR  Suzuki reaction  Gabriel reaction 
學科別分類 學科別自然科學化學
中文摘要 本研究成功利用優化之Gabriel reaction合成六個含硼之一級胺類化合物 (Fig. 1)。由於這六個含硼一級胺類化合物皆在溫和的條件下予以合成,因此所得產率皆高於50%以上 (Scheme 1,2)。
以含硼一級胺產物為Ugi多組成反應(Ugi-4CR)之起始物並藉由微波輔助條件,本研究成功合成含硼之peptoid衍生物。而這些含硼之peptoid衍生物可藉由一鍋化水解反應,將其轉變為相對應之硼酸化合物 (Fig. 2)。最後,這些Ugi-4CR之peptoids化合物可藉由Suzuki coupling reaction更進一步修飾以達到將結構複雜化的目的 (Fig. 3)。
英文摘要 In this study, the modified Gabriel synthetic condition was developed to build six boron-containing primary amines in good to excellent yields (Fig. 1). This modified condition allowed the synthesis to carry out in mild synthetic processes (Scheme 1,2).
Further, the desired boron-containing primary amines were further utilized to construct the peptoid analogs via microwave assisted Ugi four component reaction (Ugi-4CR) (Fig. 2). In addition, these Ugi-4CR boronate esters were converted to the corresponding boronic acids by a one-pot hydration reaction. Finally, the peptoid structures can be further modified by incorporating aryl/heteroaryl component via palladium mediated Suzuki coupling reaction (Fig. 3).
論文目次 目 錄
謝誌 I
中文摘要 II
英文摘要 IV
目錄 VI
圖表目錄 X
附圖目錄 XVI

Chapter 1 緒論 1
1.1 研究動機 1
1.2 研究目的 3
Chapter 2 文獻回顧 5
2.1 Peptide藥物之介紹 5
2.1.1 Peptide藥物之優缺點 5
2.1.2 Peptide藥物之改良 6
2.2 Peptoid藥物之介紹 7
2.2.1 Petoid藥物之特點 7
2.2.2 Peptoid藥物之合成 8
2.3 含硼藥物之介紹 11
2.3.1 硼化學簡介 11
2.3.1.1 硼酸(Boronic acids) 11
2.3.1.2 硼酯(Boronate esters) 13
2.3.1.3 三氟硼酸鹽類化合物(Trifluoroborates) 14
2.3.2 含硼化合物在合成上之應用 14
2.3.2.1 Metal-catalyzed cross-couplings 15
2.3.2.2 Petasis reaction 15
2.3.3含硼化合物在藥物化學上之應用 16
2.3.3.1. 酵素抑制劑 18
2.3.3.2 蛋白酶體抑制劑 27
2.3.3.3 抗癌技術與治療 32
2.3.3.4 現階段之FDA臨床藥物 34
2.4 Multiconpoment Reactions (MCRs)之介紹 36
2.4.1 MCRs之特點 36
2.4.2 Ugi Reaction之應用 41
2.4.3 含硼Ugi Reaction之介紹 46
Chapter 3 結果與討論 48
3.1 含硼一級胺之合成 48
3.1.1 BF3K amine之合成 48
3.1.2 Bpin amine之合成 53
3.1.3 Bpin amine之One-Pot合成 59
3.1.4 Bpin amine salt之合成 63
3.2 含硼一級胺之應用 66
3.2.1 Bpin Ugi之合成 66
3.2.2 B(OH)2 ugi之合成 70
3.2.3 Suzuki Reaction的合成 72
Chapter 4 結論 75
Chapter 5藥品、實驗步驟與儀器 76
5-1 藥品介紹 76
5-2 實驗儀器與測試方法 78
5-3 含硼一級胺實驗步驟 79
5-4 含硼一級胺光譜 90
5-5 含硼Ugi實驗步驟 93
5-6 含硼Ugi光譜 103
5-7 Suzuki實驗步驟 108
5-8 Suzuki光譜 111
5-9 生物活性評估與方法 113
附錄一 參考文獻 115
附錄二 光譜圖 126


圖表目錄
Fig. 1.1一般的peptide與peptoid之構型 2
Fig. 1.2含硼官能基之應用 4
Fig. 2.1各種不同peptidomimetics結構 6
Fig. 2.2硼衍生物之命名 11
Fig. 2.3常見硼酸型態 12
Fig. 2.4常見硼酯型態 13
Fig. 2.5常見硼酸鹽類型態 14
Fig. 2.6中性的三角平面之硼酸與親核試劑進行配位後會變形成陰性的四面體構型 17
Fig. 2.7最早發現的含硼天然物Boromycin 17
Fig. 2.8凝血酶抑制劑 20
Fig. 2.9凝血酶抑制劑 21
Fig. 2.10 fXa抑制劑 21
Fig. 2.11類水蛭素之凝血酶抑制劑 22
Fig. 2.12推測之水合物抑制機制 22
Fig. 2.13 α-chymotrypsin抑制劑 23
Fig. 2.14 β-lactamases抑制劑 24
Fig. 2.15 HCV抑制劑 24
Fig. 2.16 DPPIV抑制劑 25
Fig. 2.17精胺酸脢抑制劑 25
Fig. 2.18一氧化氮合酶含硼抑制劑 26
Fig. 2.19 26S蛋白酶質體 28
Fig. 2.20硼替佐米 32
Fig. 2.21硼中子捕獲治療(BNCT,Boron Neutron Capture Therapy) 33
Fig. 2.22目前應用於各類型硼之中子捕獲治療藥物 34
Fig. 2.23上圖為多步合成反應,下圖為MCRs 37
Fig. 2.24藉由MCR所開發之藥物 40
Fig. 2.25針對Ugi酸基之其他可替換官能基 42
Fig. 2.26針對Ugi胺基之其他可替換官能基 42
Fig. 2.27 Ugi環化反應之設計 43
Fig. 2.28各種不同含硼化合物 47
Fig. 3.1目標之化合物 48
Fig. 3.2推測之化合物 49
Fig. 3.3 BF3K官能基氧化為OH官能基 52
Fig. 3.4目標之化合物 53
Fig. 3.5 (a)氯化物 (b)含methyl methanesulfonate離去基之化合物 55
Fig. 3.6含硼一級胺 58
Fig. 3.7硼酸與硼酯可以藉由酸鹼度加以調控 65
Fig. 3.8進行Ugi-4CR所需起始物 67
Fig. 3.9含Bpin之Ugi-4CR產物 69
Fig. 3.10含B(OH)2之Ugi-4CR產物 71
Fig. 3.11有機鹵化物與Pd催化劑 72
Fig. 3.12 Suzuki cross-coupling之產物 73


Scheme 2.1最起初peptoid的合成 9
Scheme 2.2 peptoid的“submonomer”之固相合成 10
Scheme 2.3硼酸易受到環境pH值的改變而影響構型 12
Scheme 2.4硼酸化合物於cross-coupling之反應 15
Scheme 2.5由Petasis reaction合成出不同官能機化合物 16
Scheme 2.6硼酸化合物在四面體轉換 18
Scheme 2.7硼酸化合物對蛋白酶抑制機制簡圖 19
Scheme 2.8胱胺酸蛋白酶抑制機制 27
Scheme 2.9a Ugi反應基本的四大元素 41
Scheme 2.10 Solid-Phase MCRs of Ugi Reaction 44
Scheme 2.11 GSK藉由Ugi-4CR所合成之DKP類藥物 45
Scheme 2.12 Lemonomycin之Ugi-4CR 46
Scheme 3.1硼官能基轉換 48
Scheme 3.2含BF3K之一級胺合成步驟 51
Scheme 3.3含BF3K之一級胺合成步驟 52
Scheme 3.4 含氟之一級胺合成步驟 58
Scheme 3.5有機鹼與無機鹼在氯化反應中推測之反應機制 61
Scheme 3.6首次使用One-Pot反應合成出含硼一級胺 62
Scheme 3.7用One-Pot反應合成出含硼一級胺鹽 65
Scheme 3.8 Suzuki cross-coupling 72

Table 2.1含硼藥物之臨床試驗 34
Table 2.2大部分常見的MCRs 37
Table 2.3 MCRs的類型 40
Table 3.1含BF3K之一級胺條件測試 49
Table 3.2 B(OH)2轉Bpin官能基 54
Table 3.3 Aldehyde還原為Alcohol官能基 54
Table 3.4 Alcohol轉換為phthalimide基團 56
Table 3.5 phthalimide基團轉換為一級胺 57
Table 3.6 Alcohol轉換為phthalimide基團 59
Table 3.7一級胺轉鹽類 64
Table 3.8利用微波裝置進行Ugi-4CR之優化試驗 66
Table 3.9含硼Ugi-4CR之合成 68
Table 3.10含硼Ugi-4CR之合成 70
Table 3.11 Suzuki cross-coupling之合成 73


附圖目錄
附圖 1化合物3.8a之1H-NMR (300 MHz, CDCl3-d3) 130
附圖 2化合物3.8a之13C-NMR (75.5 MHz, CDCl3-d3) 131
附圖 3化合物3.8a之11B-NMR (192.5 MHz, CD3OD-d4) 131
附圖 4化合物3.8b之1H-NMR (300 MHz, CDCl3-d3) 132
附圖 5化合物3.8b之13C-NMR (75.5 MHz, CDCl3-d3) 132
附圖 6化合物3.8b之11B-NMR (192.5 MHz, CD3OD-d4) 133
附圖 7化合物3.8c之1H-NMR (300 MHz, CDCl3-d3) 133
附圖 8化合物3.8c之13C-NMR (75.5 MHz, CDCl3-d3) 134
附圖 9化合物3.8c之11B-NMR (192.5 MHz, CD3OD-d4) 134
附圖 10化合物3.8d之1H-NMR (300 MHz, CDCl3-d3) 135
附圖 11化合物3.8d之13C-NMR (75.5 MHz, CDCl3-d3) 136
附圖 12化合物3.8d之11B-NMR (192.5 MHz, CD3OD-d4) 136
附圖 13化合物3.8e之1H-NMR (300 MHz, CDCl3-d3) 137
附圖 14化合物3.8e之13C-NMR (75.5 MHz, CDCl3-d3) 137
附圖 15化合物3.8e之11B-NMR (192.5 MHz, CD3OD-d4) 138
附圖 16化合物3.8f之1H-NMR (300 MHz, CDCl3-d3) 138
附圖 17化合物3.8f之13C-NMR (75.5 MHz, CDCl3-d3) 139
附圖 18化合物3.8f之11B-NMR (192.5 MHz, CD3OD-d4) 139
附圖 19化合物3.12a之1H-NMR (300 MHz, CDCl3-d3) 140
附圖 20化合物3.12a之13C-NMR (75.5 MHz, CDCl3-d3) 140
附圖 21化合物3.12a之11B-NMR (192.5 MHz, CDCl3-d3) 141
附圖 22化合物3.12b之1H-NMR (300 MHz, CDCl3-d3) 141
附圖 23化合物3.12b之13C-NMR (75.5 MHz, CDCl3-d3) 142
附圖 24化合物3.12b之11B-NMR (192.5 MHz, CDCl3-d3) 142
附圖 25化合物3.12c之1H-NMR (300 MHz, CDCl3-d3) 143
附圖 26化合物3.12c之13C-NMR (75.5 MHz, CDCl3-d3) 143
附圖 27化合物3.12c之11B-NMR (192.5 MHz, CD3OD-d4) 144
附圖 28化合物3.12e之1H-NMR (300 MHz, CDCl3-d3) 144
附圖 29化合物3.12e之13C-NMR (75.5 MHz, CDCl3-d3) 145
附圖 30化合物3.12e之11B-NMR (192.5 MHz, CD3OD-d4) 145
附圖 31化合物3.12e之HMQC-2D NMR 146
附圖 32化合物3.12e之HMBC-2D NMR 146
附圖 33化合物3.12e之HMBC-2D NMR (expand) 147
附圖 34化合物3.16a之1H-NMR (300 MHz, CDCl3-d3) 148
附圖 35化合物3.16a之13C-NMR (75.5 MHz, CDCl3-d3) 148
附圖 36化合物3.16a之11B-NMR (192.5 MHz, CD3OD-d4) 149
附圖 37化合物3.16b之1H-NMR (300 MHz, CDCl3-d3) 149
附圖 38化合物3.16b之13C-NMR (75.5 MHz, CDCl3-d3) 150
附圖 39化合物3.16b之11B-NMR (192.5 MHz, CD3OD-d4) 150
附圖 40化合物3.16c之1H-NMR (300 MHz, CDCl3-d3) 151
附圖 41化合物3.16c之13C-NMR (75.5 MHz, CDCl3-d3) 151
附圖 42化合物3.16c之11B-NMR (192.5 MHz, CDCl3-d3) 152
附圖 43化合物3.16d之1H-NMR (300 MHz, CDCl3-d3) 152
附圖 44化合物3.16d之13C-NMR (75.4 MHz, CDCl3-d3) 153
附圖 45化合物3.16d之11B-NMR (192.5 MHz, CDCl3-d3) 153
附圖 46化合物3.16e之1H-NMR (300 MHz, CDCl3-d3) 154
附圖 47化合物3.16e之13C-NMR (150.9 MHz, CDCl3-d3) 154
附圖 48化合物3.16e之11B-NMR (192.5 MHz, CDCl3-d3) 155
附圖 49化合物3.17a之1H-NMR (300 MHz, CD3OD-d4) 155
附圖 50化合物3.17a之13C-NMR (75.5 MHz, CD3OD-d4) 156
附圖 51化合物3.17a之11B-NMR (192.5 MHz, CD3OD-d4) 156
附圖 52化合物3.17b之1H-NMR (300 MHz, CD3OD-d4) 157
附圖 53化合物3.17b之13C-NMR (150.9 MHz, CD3OD-d4) 157
附圖 54化合物3.17b之11B-NMR (192.5 MHz, CD3OD-d4) 158
附圖 55化合物3.17c之1H-NMR (300 MHz, CD3OD-d4) 158
附圖 56化合物3.17c之13C-NMR (75.4 MHz, CD3OD-d4) 159
附圖 57化合物3.17c之11B-NMR (192.5 MHz, CD3OD-d4) 159
附圖 58化合物3.17d之1H-NMR (300 MHz, CD3OD-d4) 160
附圖 59化合物3.17d之13C-NMR (75.4 MHz, CD3OD-d4) 160
附圖 60化合物3.17d之11B-NMR (192.5 MHz, CD3OD-d4) 161
附圖 61化合物3.17e之1H-NMR (600 MHz, CD3OD-d4) 161
附圖 62化合物3.17e之13C-NMR (75.4 MHz, CD3OD-d4) 162
附圖 63化合物3.17e之11B-NMR (192.5 MHz, CD3OD-d4) 162
附圖 64化合物3.17e之HMQC - 2D NMR 163
附圖 65化合物3.17e之HMBC - 2D NMR 164
附圖 66化合物3.19a之1H-NMR (300 MHz, CDCl3-d3) 165
附圖 67化合物3.19a之13C-NMR (150.9 MHz, CDCl3-d3) 165
附圖 68化合物3.19b之1H-NMR (300 MHz, CDCl3-d3) 166
附圖 69化合物3.19b之13C-NMR (75.5 MHz, CDCl3-d3) 166
附圖 70化合物3.19c之1H-NMR (600 MHz, CD3OD-d4) 167
附圖 71化合物3.19c之13C-NMR (150.9 MHz, CD3OD-d4) 167
附圖 72化合物3.19d之1H-NMR (600 MHz, CDCl3-d3) 168
附圖 73化合物3.19d之13C-NMR (75.5 MHz, CDCl3-d3) 168
參考文獻 1. Zuckermann, R. N.; Martin, E. J.; Spellmeyer, D. C.; Stauber, G. B.; Shoemaker, K. R.; Kerr, J. M.; Figliozzi, G. M.; Goff, D. A.; Siani, M. A.; Simon, R. J.; Banville, S. C.; Brown, E. G.; Wang, L.; Richter, L. S.; Moos, W. H. Journal of Medicinal Chemistry 1994, 37, 2678.
2. Murphy, J. E.; Uno, T.; Hamer, J. D.; Cohen, F. E. Dwarki, V.; Zuckermann, R. N. Proceedings of the National Academy of Sciences of the United States of America 1998, 95, 1517.
3. Ng, S.; Goodson, B.; Ehrhardt, A.; Moos, W. H.; Siani, M.; Winter, Bioorganic & Medicinal Chemistry 1999, 7, 1781.
4. Humet, M.; Carbonell, T.; Masip, I.; Sa’nchez-Baeza, F.; Mora, P.; Canto’ n, E.; Gobernado, M.; Abad, C.; Pe’rez- Paya’ , E.; Messeguer, A. Journal of Combinatorial Chemistry 2003, 5, 597.
5. Goodson, B.; Ehrhardt, A.; Ng, S.; Nuss, J.; Johnson, K.; Giedlin, M.; Yamamoto, R.; Moos, W. H.; Krebber, A.; Ladner, M.; Giacona, M. B.; Vitt, C.; Winter, J. Antimicrobial Agents and Chemotherapy 1999, 43, 1429.
6. Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. Journal of Medicinal Chemistry 1999, 42, 3743.
7. Miller, S. M.; Simon, R. J.; Ng, S.; Zuckermann, R. N.; Kerr, J. M.; Moos, W. H. Drug Development Research 1995, 35, 20.
8. Hruby, V. J.; Matsunaga, T. O.; Oxford University Press, 2002, 272.
9. (a) Simon, R. J.; Kania, R. S.; Zuckermann, R. N.; Huebner, V. D.; Jewell, D. A.; Banvill, S.; Ng, S.; Wang, L.; Rosenberg, S.; Marlowe, C. K.; Spellmeyer, D. C.; Tan, R.; Frankel, A. D.; Santi, D. V.; Cohen, F. E.; Bartlet, P. A. Proceedings of the National Academy of Sciences of the United States of America 1992, 89, 9367. (b) Kruijtzer, J. A. W.; Liskamp, R. M. J. Tetrahedron Letters 1995, 36, 6969. (c) Kruijtzer, J. A. W.; Hofmeijer, L. J. F.; Heerma, W.; Versluis, C.; Liskamp, R. M. J. Chemistry - A European Journal 1998, 4, 1570.
10. (a) Decicco, C. P.; Seng, J. L.; Kennedy, K. E.; Covington, M. B.; Welch, P. K.; Arner, E. C.; Magolda, R. L.; Nelson, D. J. Bioorganic & Medicinal Chemistry Letters 1997, 7, 2231. (b) Choy, N.; Choi, H.; Won, H. J.; Kim, C. R.; Yoon, H.; Kim, S. C.; Lee, T. G.; Koh, J. S. Journal of Medicinal Chemistry 1997, 7, 2635. (c) Moree,W. J.; van der Marel, G. A.; Liskamp, R. M. J. The Journal of Organic Chemistry 1995, 60, 5157. (d) Benedetti, F.; Berti, F.; Colombatti, A.; Ebert, C.; Linda, P.; Tonizzo, F. Chem. Commun. 1996, 1417. (e) Paik, S.; White, E. H. Tetrahedron 1996, 5303. (f) Gude, M.; Piarulli, U.; Potenza, D.; Salom, B.; Gennari, C. Tetrahedron Letters 1996, 47, 8589. (g) De Bont, D. B. A.; Dijkstra, G. D. H.; Den Hartog, J. A. J.; Liskamp, R. M. J. Bioorganic & Medicinal Chemistry Letters1996, 6, 3035.
11. (a) Burgess, K.; Linthicum, D. S.; Shin, H. Angewandte Chemie International Edition 1995, 34, 907. (b) Burgess, K.; Ibarzo, J.; Linthicum, D. S.; Russell, D. H.; Shin, H.; Shitangkoon, A.; Totani, R.; Zhang, A. J. Journal of the American Chemical Society 1997, 119, 1556.
12. (a) Barre, C.; Le Grel, P.; Robert, A.; Bandy-Flock, M. Journal of the Chemical Society, Chemical Communications 1994, 607. (b) Han, H.; Janda, K. D. Journal of the American Chemical Societ 1996, 118, 2539.
13. Fowler, S. A., Luechapanichkul, R., Blackwell, H. E. Journal of Organic Chemistry 2009, 74, 4, 1440.
14. Chongsiriwatana, N. P.; Patch, J. A.; Czyzewski, A. M.; Dohm, M. T.; Ivankin, A.; Gidalevitz, D.; Zuckermann, R. N.; Barron, A. E. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 2794.
15. Seurynck-Servoss, S. L.; Dohm, M. T.; Barron, A. E. Biochemistry 2006, 45, 11809.
16. Li, S.; Bowerman, D.; Marthandan, N.; Klyza, S.; Luebke, K. J.; Garner, H. R.; Kodadek, T. Journal of the American Chemical Society 2004, 126, 4088.
17. Liu, B.; Alluri, P. G.; Yu, P.; Kodadek, T. Journal of the American Chemical Society 2005, 127, 8254.
18. Hara, T.; Durell, S. R.; Myers, M. C.; Appella, D. H. Journal of the American Chemical Society 2006, 128, 1995.
19. Maayan, G.; Ward, M. D.; Kirshenbaum, K. Proceedings of the National Academy of Sciences of the United States of America 2009, 106, 13679.
20. Lee, B.-C.; Chu, T. K.; Dill, K. A.; Zuckermann, R. N. Journal of the American Chemical Society 2008, 130, 8847.
21. (a) Waters, M. L. Biopolymers 2004, 76, 435. (b) Waters, M. L. Current Opinion in Chemical Biology 2002, 6, 736.
22. (a) Graciani, N. R.; Tsang, K. Y.; McCutchen, S. L.; Kelly, J. W. Bioorganic & Medicinal Chemistry 1994, 2, 999. (b) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore, J. S. Journal of the American Chemical Society 1999, 121, 3114. (c) Gabriel, G. J.; Sorey, S.; Iverson, B. L. Journal of the American Chemical Society 2005, 127, 2637. (d) Mahalakshmi, R.; Raghothama, S.; Balaram, P. Journal of the American Chemical Society 2006, 128, 1125. (e) Hu, Z.-Q.; Hu, H.-Y.; Chen, C.-F. The Journal of Organic Chemistry 2006, 71, 1131.
23. (a) Armand, P.; Kirshenbaum, K.; Goldsmith, R. A.; Farr-Jones, S.; Barron, A. E.; Truong, K. T.; Dill, K. A.; Mierke, D. F.; Cohen, F. E.; Zuckermann, R. N.; Bradley, E. K. Proceedings of the National Academy of Sciences of the United States of America 1998, 95, 4309. (b) Armand, P.; Kirshenbaum, K.; Falicov, A.; Dunbrack, R. L. Jr.; Dill, K. A.; Zuckermann, R. N.; Cohen, F. E. Folding and Design 1997, 2, 369.
24. For an excellent review of aromatic-aromatic interactions, see: Meyer, E. A.; Castellano, R. K.; Diederich, F. Angewandte Chemie International Edition 2003, 42, 1210.
25. Carosi, L.; Hall, D. G. Angewandte Chemie, International Edition 2007, 46, 31, 5913.
26. Jego, J. M.; Carboni, B.; Vaultier, M. Journal of Organometallic Chemistry 1992, 1, 435.
27. Fandrick, D. R.; Reeves, J. T.; Tan, Z.; Lee, H.; Song, J. J.; Yee, N. K.; Senanayake, C. H. Organic Letters 2009, 11, 23, 5458.
28. Eran, S.; Doron, S. Journal of the American Chemical Society 2009, 131, 29, 9934.
29. Nunez, S. A.; Yeung, K.; Fox, N. S.; Phillips, S. T. Journal of Organic Chemistry 2011, 76, 24, 10099.
30. Ulijn, R. V., Smith, A. M. Chemical Society Reviews 2008, 37, 664.
31. Zhao, X., Pan, F., Lu, J. R. Progress in Natural Science, 2008, 18, 653.
32. Stryer, L. Biochemistry 1988.
33. Paramonov, S. E., Jun, H. W., Hartgerink, J. D. Journal of the American Chemical Society 2006, 128, 7291.
34. Ranganathan, D., Lakshmi, C., Karle, I. L. Journal of the American Chemical Society 1999, 121, 6103.
35. Haldar, D., Maji, S. K., Drew, M. G. B., Banerjee, A. Tetrahedron Letters 2002, 43, 5465.
36. Ghadiri, M. R., Granja, J. R., Milligan, R. A., McRee, D. E., Khazanovich, N. Nature, 1993, 366, 324.
37. Hartgerink, J. D., Granja, J. R., Milligan, R. A., Ghadiri, M. R. Journal of the American Chemical Society 1996, 118, 43.
38. Khoe, U., Yang, Y., Zhang, S. Macromolecular Bioscience, 2008, 8, 1060.
39. von-Maltzahn, G., Vauthey, S., Santoso, S., Zhang, S. Langmuir 2003, 19, 4332.
40. Nagai, A., Nagai, Y., Qu, H., Zhang, S. Journal of Nanoscience and Nanotechnology 2007, 7, 2246.
41. Santoso, S., Hwang, W., Hartman, H., Zhang, S. Nano Letters 2002, 2, 687.
42. Khoe, U., Yang, Y., Zhang, S. Langmuir 2009, 25, 4111.
43. Yang, H., Fung, S.-Y. Pritzker, M., Chen, P. PLoS One 2007, 2, 1325.
44. Cousins, B. G., Das, A. K., Sharma, R., Li, Y., McNamara, J. P., Hillier, I. H., Kinloch, I. A., Ulijn, R. V., Small 2009, 5, 587.
45. Das, A. K., Collins, R., Ulijn, R. V. Small 2008, 4, 279.
46. Toledano, S., Williams, R. J., Jayawarna, V., Ulijn, R. V. Journal of the American Chemical Society 2006, 128, 1070.
47. Laromaine, A., Koh, L., Murugesan, M., Ulijn, R. V., Stevens, M. M. Journal of the American Chemical Society 2007, 129, 4156.
48. Fowler, S. A., Luechapanichkul, R., Blackwell, H. E. Journal of Organic Chemistry 2009, 74, 4, 1440.
49. Tan, N.C., Yu, P., Kwon, Y., Kodadek, T. Bioorganic & Medicinal Chemistry 2008, 16, 5853.
50. Simon, R. J., Kania, R. S., Zuckermann, R. N., Huebner, V. D., Jewell, D. A., Banville, S., Ng, S. Wang, L., Rosenberg, S., Marlowe, C. K., Spellmeyer, D. C., Tan, R., Frankel, A. D., Santi, D. V., Cohen, F. E., Bartlett, P. A. Proceedings of the National Academy of Sciences of the United States of America 1992, 89, 9367.
51. Zuckermann, R. N., Kerr, J. M., Kent, S. B. H., Moos, W. H. Journal of the American Chemical Society 1992, 114, 10646.
52. Wender, P. A., Mitchell, D. J., Pattabiraman, K., Pelkey, E. T., Steinman, L., Rothbard, J. B. Proceedings of the National Academy of Sciences of the United States of America 2000, 97, 13003.
53. Schroder, T., Schmitz, K., Niemeier, N., Balaban, T. S., Krug, H. F. Bioconjugate Chemistry 2007, 18, 342.
54. Fowler, S. A., Blackwell, H. E. Organic & Biomolecular Chemistry 2009, 7, 1508.
55. Liu, B., Alluri, P. G., Yu, P., Kodadek, T. Journal of the American Chemical Society 2005, 127, 8254.
56. Olivos, H. J., Alluri, P. G., Reddy, M. M., Salony, D., Kodadek, T. Organic Latters 2002, 4, 23, 4057.
57. Elgersma, R. C., Mulder, G. E., Kruijtzer, J. A. W., Posthuma, G., Rijkers, D. T. S., Liskamp, R. M. J. Bioorganic & Medicinal Chemistry Letters 2007, 17, 1837.
58. Simon, R.J., Kania, R.S., Zuckermann, R.N., Huebner, V.D., Jewell, D.A., Banville, S., Ng, S., Wang, L., Rosenberg, S., Marlowe, C.K., Spellmeyer, D.C. Proceedings of the National Academy of Sciences of the United States of America 1992, 89, 20, 9367.
59. Zuckermann, R. N., Kerr, J. M., Kent, S. B. H., Journal of the American Chemical Society 1992, 114, 26, 10646.
60. Zuckermann,R. N., Kerr, J. M., Kent, S. B. H., Moos, W. H. Journal of the American Chemical Society 1992, 114, 10646.
61. Olivos, H. J., Alluri, P. G., Reddy, M. M., Salony, D., Kodadek, T. Organic Letters 2002, 4, 4057.
62. Nnanabu, E., Burgess, K. Organic Letters 2006, 8, 1259.
63. Gorske, B. C., Jewell, S. A., Guerard, E. J., Blackwell, H. E. Organic Letters 2005, 7, 1521.
64. Hall, D. G. Wiley-VCH 2005.
65. Hall, D. G. Wiley-VCH 2005.
66. Petasis, N. A., Zavialov, I. A. Journal of the American Chemical Society 1997, 119, 445.
67. Kumagai, N., Muncipinto, G., Schreiber, S. L. Angewandte Chemie International Edition 2006, 45, 3635.
68. Petasis, N. A., Zavialov, I. A. Journal of the American Chemical Society 1998, 120, 11798.
69. Brown, H. C., Ramachandran, P. V. Accounts of Chemical Research 1992, 25, 16.
70. Yamamoto, Y., Asao, N. Chemical Reviews 1993, 93, 2207.
71. Hernandez, E., Canales, E., Gonzalez, E., Soderquist, J. A. Pure and Applied Chemistry 2006, 78, 1389.
72. Ramachandran, P. V., Burghardt, T. E. Pure and Applied Chemistry 2006, 78, 1397.
73. Roy, C. D., Brown, H. C. Australian Journal of Chemistry 2007, 60, 835.
74. Corey, E. J., Shibata, S., Bakshi, R. K. The Journal of Organic Chemistry 1988, 53, 2861.
75. Braunschweig, H., Dewhurst , R. D., Schneider, A. Chemical Reviews 2010, 110, 3924.
76. Levonis, S. M., Bornaghi, L. F., Houston, T. A. Australian Journal of Chemistry 2007, 60, 821.
77. Yan, J., Fang, H., Wang, B. Medicinal Research Reviews 2005, 25, 490.
78. Jin, S., Cheng, Y., Reid, S., Li, M., Wang, B. Medicinal Research Reviews 2010, 30, 171.
79. Wade, C. R., Broomsgrove, A. E. J., Aldridge, S., Gabbaı‥, F. P. Chemical Reviews 2010, 110, 3958.
80. Wade, C. R., Gabbaı‥, F. P. Inorganic Chemistry 2010, 49, 714.
81. Baker, S. J., Ding, C. Z., Akama, T., Zhang, Y. K., Hernandez, V., Xia, Y. Future Medicinal Chemistry 2009, 1, 1275.
82. Groziak, M. P. American Journal of Therapeutics 2001, 8, 321.
83. Yang, W., Gao, X., Wang, B. H. Medicinal Research Reviews 2003, 23, 346.
84. Hutter, R., Keller-Schierlein, W., Knusel, F., Prelog, V., Rodgers, G. C., Suter, P., Vogel, G., Voser, W., Zahner, H. Helvetica Chimica Acta 1967, 50, 1533.
85. Pache, W., Zahner, H. Archives of Microbiology 1969, 67, 156.
86. Kohno, J., Kawahata, T., Otake, T., Morimoto, M., Mori, H., Ueba, N., Nishio, M., Kinumaki, A., Komatsubara, S., Kawashima, K. Bioscience, Biotechnology, and Biochemistry 1996, 60, 1036.
87. Springsteen, G., Wang, B. Tetrahedron 2002, 58, 5291.
88. Wiskur, S. L., Lavigne, J. J., Ait-Haddou, H., Lynch, V., Chiu, Y. H., Canary, J. W., Anslyn, E. V. Organic Letters 2001, 3, 1311.
89. Liu, X.-C., Hubbard, J. L., Scouten, W. H. Journal of Organometallic Chemistry 1995, 493, 91.
90. Lienhard, G. E., Koehler, K. A. Biochemistry 1971, 10, 2477.
91. Philipp, M., Bender, M. L. Proceedings of the National Academy of Sciences 1971, 68, 478.
92. Matthews, D. A., Alden, R. A., Birktoft, J. J., Freer, S. T., Kraut, J. Journal of Biological Chemistry 1975, 250, 7120.
93. Hiratake, J., Oda, J. i. Bioscience, Biotechnology, and Biochemistry 1997, 61, 211.
94. Kettner, C., Mersinger, L., Knabb, R. Journal of Biological Chemistry 1990, 265, 18289.
95. Fevig, J. M., Abelman, M. M., Brittelli, D. R., Kettner, C. A., Knabb, R. M., Weber, P. C. Bioorganic & Medicinal Chemistry Letters 1996, 6, 295.
96. Cacciola, J., Fevig, J. M., Alexander, R. S., Brittelli, D. R., Kettner, C. A., Knabb, R. M., Weber, P. C. Bioorganic & Medicinal Chemistry Letters 1996, 6, 301.
97. Fevig, J. M., Buriak Jr, J., Cacciola, J., Alexander, R. S., Kettner, C. A., Knabb, R. M., Pruitt, J. R., Weber, P. C., Wexler, R. R. Bioorganic & Medicinal Chemistry Letters 1998, 8, 301.
98. Cacciola, J., Fevig, J. M., Stouten, P. F. W., Alexander, R. S., Knabb, R. M., Wexler, R. R. Bioorganic & Medicinal Chemistry Letters 2000, 10, 1253.
99. Lee, S.-L., Alexander, R. S., Smallwood, A., Trievel, R., Mersinger, L., Weber, P. C., Kettner, C. Biochemistry 1997, 36, 13180.
100. Elgendy, S., Patel, G., Green, D., Goodwin, C. A., Scully, M. F., Husman, W., Skordalakes, E., Kakkar, V. V., Deadman, J. J. Tetrahedron Letters 1997, 38, 3305.
101. Tian, Z.-Q., Brown, B. B., Mack, D. P., Hutton, C. A., Bartlett, P. A. The Journal of Organic Chemistry 1997, 62, 514.
102. Bonomo, R., Rice, L. Front Biosci 1999, 4, 34.
103. Strynadka, N. C. J., Adachi, H., Jensen, S. E., Johns, K., Sielecki, A., Betzel, C., Sutoh, K., James, M. N. G. Nature 1992, 359, 700.
104. Strynadka, N. C. J., Martin, R., Jensen, S. E., Gold, M., Jones, J. B. Nature Structural & Molecular Biology 1996, 3, 688.
105. Ness, S., Martin, R., Kindler, A. M., Paetzel, M., Gold, M., Jensen, S. E., Jones, J. B., Strynadka, N. C. J. Biochemistry 2000, 39, 5312.
106. Kwong, A. D. Current Opinion in Infectious Diseases 1997, 10, 485.
107. Attwood, M. R., Bennett, J. M., Campbell, A. D., Canning, G. G., Carr, M. G., Conway, E., Dunsdon, R. M., Greening, J. R., Jones, P. S., Kay, P. B., Handa, B. K., Hurst, D. N., Jennings, N. S., Jordan, S., Keech, E., O'Brien, M. A., Overton, H. A., King-Underwood, J., Raynham, T. M., Stenson, K. P., Wilkinson, C. S., Wilkinson, T. C., Wilson, F. X. Antivir Chem Chemother 1999, 10, 259.
108. Dunsdon, R. M., Greening, J. R., Jones, P. S., Jordan, S., Wilson, F. X. Bioorganic &, Medicinal Chemistry Letters 2000, 10, 1577.
109. Demuth, H. U., Baumgrass, R., Schaper, C., Fischer, G., Barth, A. Journal of Enzyme Inhibition and Medicinal Chemistry 1988, 2, 129.
110. Boduszek, B., Oleksyszyn, J., Kam, C.-M., Selzler, J., Smith, R. E., Powers, J. C. Journal of Medicinal Chemistry 1994, 37, 3969.
111. Flentke, G. R., Munoz, E., Huber, B. T., Plaut, A. G., Kettner, C. A., Bachovchin, W. W. Proceedings of the National Academy of Sciences 1991, 88, 1556.
112. Kanyo, Z. F., Scolnick, L. R., Ash, D. E., Christianson, D. W. Nature 1996, 383, 554.
113. Baggio, R., Elbaum, D., Kanyo, Z. F., Carroll, P. J., Cavalli, R. C., Ash, D. E., Christianson, D. W. Journal of the American Chemical Society 1997, 119, 8107.
114. Lebarbier, C., Carreaux, F., Carboni, B., Boucher, J. L. Bioorganic &, Medicinal Chemistry Letters 1998, 8, 2573.
115. Martichonok, V., Bryan Jones, J. Bioorganic &, Medicinal Chemistry 1997, 5, 679.
116. Peters, J. M., Franke, W. W., Kleinschmidt, J. A. The Journal of Biological Chemistry 1994, 269, 10, 7709.
117. Lodish, H., Berk A., Matsudaira, P., Kaiser, C. A., Krieger, M., Scott, M. P., Zipursky, S. L., Darnell, J. Molecular Cell Biology 2004, 5, 3, 66.
118. Davie, E. The Journal of Biological Chemistry 2003, 278, 50819.
119. Angelman, H. Developmental Medicine & Child Neurology 1965, 7, 681.
120. Mori, H., Kondo, J.,, Ihara, Y. Science 1987, 235, 1641.
121. Lodish, H., Berk, A., Matsudaira, P., Kaiser, C. A., Krieger, M., Scott, M. P., Zipursky, S. L., Darnell, J. Molecular Cell Biology 2004, 5, 3, 66.
122. Lodish, H., Berk, A., Matsudaira, P., Kaiser, C. A., Krieger, M., Scott, M. P., Zipursky, S. L., Darnell, J. Molecular Cell Biology 2004, 5, 3, 66.
123. Chesnel, F., Bazile, F., Pascal, A., Kubiak, J. Z. Cell Cycle 2006, 5, 15, 1687.
124. Havens, C. G., Ho, A., Yoshioka, N., Dowdy, S. F. Molecular and Cellular Biology 2006, 26, 12, 4701.
125. Bashir, T., Dorrello, N. V., Amador, V., Guardavaccaro, D., Pagano, M. Nature 2004, 428, 6979, 190.
126. Dharmasiri, S., Estelle, M. Plant Molecular Biology 2002, 49, 3-4, 401.
127. Weijers, D., Benkova, E., Jager, K. E., Schlereth, A., Hamann, T., Kientz, M., Wilmoth, J. C., Reed, J. W., Jurgens, G. The EMBO Journal , 2005, 24, 10, 1874.
128. Haas, A. L., Warms, J. V., Hershko, A., Rose, I. A. The Journal of Biological Chemistry 1982, 257, 5, 2543.
129. Schwartz, L. M., Myer, A., Kosz, L., Engelstein, M., Maier, C. Neuron 1990, 5, 411.
130. Low, P., Bussell, K., Dawson, S. P., Billett, M. A., Mayer, R. J., Reynolds, S. E. FEBS Letters 1997, 400, 345.
131. Pitzer, F., Dantes, A., Fuchs, T., Baumeister, W., Amsterdam, A. FEBS Letters 1996, 394, 47.
132. Orlowski, R. Z. Cell Death & Differentiation 1999, 6, 303.
133. U.S. Food and Drug Administration
134. Fisher, R. I., Bernstein, S. H., Kahl, B. S., Djulbegovic, B., Robertson, M. J., de Vos, S., Epner, E., Krishnan, A., Leonard, J. P., Lonial, S., Stadtmauer, E. A., O'Connor, O. A., Shi, H., Boral, A. L., Goy, A. Journal of Clinical Oncology 2006, 24, 30, 4867.
135. Jakob, C., Egerer, K., Liebisch, P., Turkmen, S., Zavrski, I., Kuckelkorn, U., Heider, U., Kaiser, M., Fleissner, C., Sterz, J., Kleeberg, L., Feist, E., Burmester, G. R., Kloetzel, P. M., Sezer, O. Blood First Edition 2006.
136. Shah, S. A., Potter, M. W., McDade, T. P., Ricciardi, R., Perugini, R. A., Elliott, P. J., Adams, J., Callery, M. P. Journal of Cellular Biochemistry 2001, 82, 1, 110.
137. Nawrocki, S. T., Sweeney-Gotsch, B., Takamori, R., McConkey, D. J. Molecular Cancer Therapeutics 2004, 3, 1, 59.
138. Schenkein, D. Clinical Lymphoma, Myeloma & Leukemia 2002, 3, 1, 49.
139. O'Connor, O. A., Wright, J., Moskowitz, C., Muzzy, J., MacGregor-Cortelli, B., Stubblefield, M., Straus, D., Portlock, C., Hamlin, P., Choi, E., Dumetrescu, O., Esseltine, D., Trehu, E., Adams, J., Schenkein, D., Zelenetz, A. D. Journal of Clinical Oncology 2005, 23, 4, 676.
140. Soloway, A. H., Tjarks, W., Barnum, B. A., Rong, F. G., Barth, R. F., Codogni, I. M., Wilson, J. G. Chemical Reviews 1998, 98, 1515.
141. Kruger, G. Proceedings of the National Academy of Sciences of the United States of America 1940, 26, 181.
142. Adams, J. The Discovery and Selection of Successful Drug Candidates 2007.
143. Baker, S. J., Ding, C. Z., Akama, T., Zhang, Y. K., Hernandez, V., Xia, Y. Future Medicinal Chemistry 2009, 1, 7, 1275.
144. Wender, P. A., Handy, S. T., Wright, D. L. Chemistry & Industry 1997, 765, 767.
145. Gaich, T., Baran, P. S. The Journal of Organic Chemistry 2010, 75, 4657.
146. Zhu, J., Bienayme, H., Wiley-VCH 2005.
147. Ugi, I., Domling, A., Horl, W. Endeavour 1994, 18, 115.
148. Tietze, L. F. Chemical Reviews 1996, 96, 115.
149. Passerini, M. Gazzetta Chimica Italiana 1921, 51, 126.
150. Van Leusen, D., Van Leusen, A. M. Organic Reactions 2003, 57, 419.
151. Strecker, A. Ann. Chem. Pharm. 1854, 91, 349.
152. Hantzsch, A. Chemische Berichte 1881, 14, 1637.
153. (a) Biginelli, P. Chemische Berichte 1891, 24, 1317. (b) Biginelli, P. Chemische Berichte 1891, 24, 2962. (c) Kappe, C. O. Tetrahedron 1993, 49, 6937.
154. Mannich, C. Journal of the Chemical Society 1917, 112, 634.
155. ADomling, A., Wang, W., Wang, K. Chemical Reviews 2012, 112, 3083.
156. Domling, A. Chemical Reviews 2006, 106, 17.
157. Zhu, J., Bienayme, H., Wiley-VCH 2005.
158. Ugi, I., Werner, B., Domling, A. Molecules 2003, 8, 53.
159. El Kaim, L., Grimaud, L. Tetrahedron 2009, 65, 2153.
160. Domling , A., Ugi, I. Angewandte Chemie International Edition 2000, 39, 3168.
161. Kehagia, K., Ugi, I. K. Tetrahedron 1995, 51, 35, 9523.
162. Banfi, L., Wiley-VCH 2005, 1.
163. Tempest, P. A., Brown, S. D., Armstrong, R. W. Angewandte Chemie, International Edition in English 1996, 35, 640.
164. Oertel, K., Zech, G., Kunz, H. Angewandte Chemie International Edition 2000, 39, 8, 1431.
165. Chen, J. J., Golebiowski, A., Klopfenstein, S. R., West, L. Tereahedron Letters 2002, 43, 22, 4083.
166. Corey, R. B. Journal of the American Chemical Society 1938, 60, 7, 1598.
167. Martins, M. B., Carvalho, I. Tetrahedron 2007, 63, 40, 9923.
168. Nicholson, B., Lloyd, G. K., Miller, B. R., Palladino, M. A., Kiso, Y., Hayashi, Y., Neuteboom, S. T. Anti-Cancer Drugs 2006, 17, 1, 25.
169. Sinha, S., Srivastava, R., de Clercq, E., Singh, R. K. Nucleosides, Nucleotides and Nucleic Acids 2004, 23, 12, 1815.
170. Houston, D. R., Synstad, B., Eijsink, V. G., Stark, M. J., Eggleston, I. M., van Aalten, D. M. Journal of Medicinal Chemistry 2004, 47, 23, 5713.
171. Kwon, O. S., Park, S. H., Yun, B.-S., Pyun, Y. R., Kim, C.-J. Journal of Antibiotics 2000, 53, 9, 954.
172. Whaley, H. A., Patterson, E. L., Dann, M., Shay, A. J., Porter, J. N. Antimicrobial Agents and Chemotherapy 1964, 8, 83-86.
173. Lemonomycin was originally known as LL-AP191.
174. Rikimaru, K., Mori, K., Kan, T., Fukuyama, T. Chemical Communications 2005, 3, 394-396.
175. Miyaura, N., Suzuki, A., Chemical Reviews 1995, 95, 2457.
176. Gamsey, S., Miller, A., Olmstead, M.M., Beavers, C.M., Hirayama, L.C., Pradhan, S., Wessling, R.A., Singaram, B. Journal of the American Chemical Society 2007, 129, 1278
177. Ugolotti, J., Hellstorm, S., Britovsek, G. J. P., Jones, T. S., Hunt, P., White, A. J. P. Dalton Transactions 2007, 1425.
178. Stolowitz, M. L., Ahlem, C., Hughes, K. A., Kaiser, R. J., Kesicki, E. A., Li, G., Lund, K. P., Torkelson, S. M., Wiley, J. P. Bioconjugate Chemistry 2001, 12, 229.
179. Adams, J. Cancer Treatment Reviews 2003, 29, 3.
180. Lenz, H. -J. Cancer Treatment Reviews 2003, 29, 41.
181. Soloway, A. H., Tjarks, W., Barnum, B. A., Rong, F. -G., Barth, R. F., Codogni, I. M., Wilson, J. G. Chemical Reviews 1998, 98, 1515.
182. Rock, F. L., Mao, W., Yaremchuk, A., Tukalo, M., Crepin, T., Zhou, H., Zhang, Y. -K., Hernandez, V., Akama, T., Baker, S. J., Plattner, J. J., Shapiro, L., Martinis, S. A., Benkovic, S. J., Cusack, S., Alley, M. R. K. Science 2007, 316, 1759.
183. Molander, G. A., Cavalcanti, L. N. The Journal of Organic Chemistry 2011, 76, 623.
184. Zeynizadeh, B., Setamdideh, D. Journal of the Chinese Chemical Society 2005, 52, 1179.
185. Yaping, W., Yonggang, L., Yulin, L., Guojun, Z., Yi, L. 2009 C. N. Patent, No. 20090111994.
186. Bauer, J., Rademann, J. Tetrahedron Letters 2003, 44, 5019.
187. Zhong, Q., Ngim, K. K., Sun, M., Li, J., Deese, A., Chetwyn, N. P. Journal of Chromatography A 2012, 1229, 216.
188. Miyaura, N., Suzuki, A. Journal of the Chemical Society, Chemical Communications 1979, 886.
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