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系統識別號 U0002-2207202014284300
中文論文名稱 利用含硼異腈合成depsipeptide衍生物
英文論文名稱 Synthesis of Borodepsipeptides using Boron-containing Isocyanides
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 108
學期 2
出版年 109
研究生中文姓名 江曜宇
研究生英文姓名 Yao-Yu Chiang
學號 608160106
學位類別 碩士
語文別 英文
口試日期 2020-06-29
論文頁數 46頁
口試委員 指導教授-潘伯申
委員-陳一瑋
委員-謝忠宏
中文關鍵字 帕瑟里尼反應  多組成反應  硼酸  微波 
英文關鍵字 Passerini  Multicomponent Reaction  Boronic Acid  Microwave 
學科別分類 學科別自然科學化學
中文摘要 自從發現含硼的Passerini反應以來,報導主要集中在將含硼的羧酸或醛作為唯一的結構單元。部分原因是由於通常將含硼異氰酸酯視為不穩定的材料,不適合合成應用。這項研究提供了證據,證明含硼異氰酸酯足夠穩定,可以用作原料。此外,異氰基可用於多種合成目的,這使其成為有機化學家非常有價值的官能團。在此,描述了利用含硼異氰酸酯合成硼二肽的方法。通過Passerini三組分反應(P-3CR)合成目標化合物,其中H2O被用作溶劑。此外,與通常需要路易斯酸催化劑的常規P-3CR不同,所報導的方法不需要催化劑,並且可以在室溫下進行。各種醛和酸被用作生成所需產物的基礎。
英文摘要 Since the discovery of the boron-containing Passerini reaction, reports are mainly focusing on having boron-containing carboxylic acids or aldehydes as the only building blocks. This is partly due to the fact that boron-containing isocyanides are generally perceived as the unstable materials that are not suitable for synthetic applications. This study provided evidence that boron-containing isocyanide is stable enough that can be used as the starting material. Further, isocyano group could serve multiple synthetic purposes that make it very valuable functional group for the organic chemists (Scheme 1).

Herein, the synthesis of borodepsipeptides utilizing boron-containing isocyanide is described. The target compounds were synthesized via Passerini three component reaction (P-3CR), in which H2O was uti-lized as the solvent. Further, unlike conventional P-3CR, where Lewis acid catalysts are often required, the reported method requires no cata-lyst and proceeds in room temperature. A variety of aldehydes and ac-ids were used as the building blocks to generate the desired products.
論文目次 Main Directory
Acknowledgement I
Abstract IV
Main Directory VI
Graph Appendix VII
Spectrum Directory VIII
Chapter 1 Introduction 1
1.1Multicomponent reaction 1
1.2Passerini MCRs 2
1.3Depsipeptide 3
1.4Boron-containing pharmaceuticals 4
1.5Research motivation 6
Chapter 2 Synthesis of Borodepsipeptides Using Boron-Containing Isocyanides 6
2.1 Passerini-3CR results in laboratory & research purpose 6
2.2 Results and Discussion 7
2.3 Conclusion 13
Chapter 3 Chemicals & Instrument 14
3.1 Chemicals 14
3.2 Instruments 16
Chapter 4 Experimental Procedure 17
Appendix 1 Spectrum Data 27
Appendix 2 Reference 45

Graph Appendix
Figure 1 Ideal Multicomponent Reaction conditions 1
Figure 2 Depsipeptide structure 3
Figure 3 FDA approved depsipeptide drugs 4
Figure 4 Boron drugs approved or in clinical trials by USFDA 5
Figure 5 Boron-containing Passerini reaction strategies 7
Figure 6 Isocyanide before microwave heating 8
Figure 7 Isocyanide after microwave heating 9

Scheme 1 Different used of boron-containing isocyanide V
Scheme 2 Passerini reaction mechanism 3

Table 1. Boron containing isocyanide Passerini reaction condition 10
Table 2 Passerini derivatives 12

Spectrum Directory
Spectrum 1 1H-NMR (600 MHz,CD3OD-d1 ) of (4) 29
Spectrum 2 13C-NMR (600 MHz, CDCl3-d1) of (4) 30
Spectrum 3 11B-NMR (600 MHz, CDCl3-d1) of (4) 30
Spectrum 4 1H-NMR (600 MHz, CDCl3-d1) of (5) 31
Spectrum 5 13C-NMR (600 MHz, CDCl3-d1) of (5) 31
Spectrum 6 11B-NMR (600 MHz, CDCl3-d1) of (5) 32
Spectrum 7 1H-NMR (600 MHz, CDCl3-d1) of (6) 32
Spectrum 8 13C-NMR (600 MHz, CDCl3-d1) of (6) 33
Spectrum 9 11B-NMR (600 MHz, CDCl3-d1) of (6) 33
Spectrum 10 1H-NMR (600 MHz, CDCl3-d1) of (7) 34
Spectrum 11 13C-NMR (600 MHz, CDCl3-d1) of (7) 34
Spectrum 12 11B-NMR (600 MHz, CDCl3-d1) of (7) 35
Spectrum 13 1H-NMR (600 MHz, CDCl3-d1) of (8) 35
Spectrum 14 13C-NMR (600 MHz, CDCl3-d1) of (8) 36
Spectrum 15 11B-NMR (600 MHz, CDCl3-d1) of (8) 36
Spectrum 16 1H-NMR (600 MHz, CDCl3-d1) of (9) 37
Spectrum 17 13C-NMR (600 MHz, CDCl3-d1) of (9) 37
Spectrum 18 11B-NMR (600 MHz, CDCl3-d1) of (9) 38
Spectrum 19 1H-NMR (600 MHz, CDCl3-d1) of (10) 38
Spectrum 20 13C-NMR (600 MHz, CDCl3-d1) of (10) 39
Spectrum 21 11B-NMR (600 MHz, CDCl3-d1) of (10) 39
Spectrum 22 1H-NMR (600 MHz, CDCl3-d1) of (11) 40
Spectrum 23 13C-NMR (600 MHz, CDCl3-d1) of (11) 40
Spectrum 24 11B-NMR (600 MHz, CDCl3-d1) of (11) 41
Spectrum 25 1H-NMR (600 MHz, CDCl3-d1) of (12) 41
Spectrum 26 13C-NMR (600 MHz, CDCl3-d1) of (12) 42
Spectrum 27 11B-NMR (600 MHz, CDCl3-d1) of (12) 42
Spectrum 28 1H-NMR (600 MHz, CDCl3-d1) of (13) 43
Spectrum 29 13C-NMR (600 MHz, CDCl3-d1) of (13) 43
Spectrum 30 11B-NMR (600 MHz, CDCl3-d1) of (13) 44
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2 Haste Nina M; Perera, Varahenage R; Maloney, Katherine N; Tran, Dan N; Jensen, Paul; Fenical, William; Nizet, Victor; Hensler, Mary E. Journal of Antibiotics. 2010, 63 (5) 219.
3 Multicomponent Reactions in Organic Synthesis, pp. 1-12
4 Ichikawa Y., Yamasaki T., Nakanishi K., Udagawa Y., Hosokawa S. and Masuda T. Synthesis. 2019, 51, 2305
5 Kreye O., Tóth T. and Meier M.A.R., Journal of the American Chemical Society. 2011, 133, 6
6 Alizadeh A., Oskueyan Q. and Rostamnia S., Synthetic Communica-tions. 2008,38, 24
7 Michel K. H., Kastner R. E. (Eli Lilly and Company), US 4492650, Chem. Abstr. 1985, 102
8 Osada, Hiroyuki, Tatsuya Yano, Hiroyuki Koshino, and Kiyoshi Isono. "Enopeptin A, a novel depsipeptide antibiotic with anti-bacteriophage activity." The Journal of Antibiotics 1991, 44, 12, 1463-1466.
9 Petasis N. A ., Zavialov I.A. J. Am. Chem. Soc. 1997, 119, 445-446.
10 Shabaan S., Ba L.A., Abbas M., Burkholz T., Denkert A., Gohr A., Wessjohann L.A., Sasse F., Weber W. and Jacob C., Chem. Commun. 2009, 31, 4702
11 Kazemizadeh A.R., Ramazani A., Current Organic Chemistry. 2012, 16, 418
12 Hattori Y., Ishimura M., Ohta Y., Takenaka H. and Kirihata M. ACS Sensors 2016, 1, 12
13 Baker S. J., Ding C. Z., Akama T., Zhang Y. K., Hernandez V., Xia Y. Med. Chem. 2009, 7, 1275-1288.
14 Bhaskar C Das,* Pritam Thapa, Radha Karki, Caroline Schinke, Sasmita Das, Suman Kambhampati, Sushanta K Banerjee, Peter Van Veldhuizen, Amit Verma, Louis M Weiss, and Todd Evans, Future Med Chem. 2013, 5(6), 653–676
15 Adams J., Kauffman M. D. Cancer Invest. 2004, 2, 304-311
16 Das B. C., Thapa P., Karki R., Schinke C., Das S., Kambhampati S., Banerjee S. K., Veldhuizen P. Van, Verma A., Weiss L. M., Evans T. Future medicinal chemistry 2013, 5, 6
17 Fang H. P., Fu C. C., Tai C. K., Chang K. H., Yang R. H., Wu M. J., Chen H. C., Li C. J., Huang S. Q., Lien W. H., Chen C. H., Hsieh C. H., Wang B. C., Cheung S. F., Pan P. S., RSC Advances 2016, 6, 36
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