臺灣博碩士論文加值系統

　　gamma-內醯胺所衍生的抗HIV化合物已經在許多文獻上被發表出來，如以Amprenavir和Indinavir為基礎所做出的gamma-內醯胺化合物，都成功的與蛋白&;#37238;結合而抑制其作用，因為合成出此類化合物的起始物就為gamma-內醯胺，所以發展出合成gamma-內醯胺的化合物，使有利於進行下一步的合成。利用三級膦的化合物與稀炔和亞胺進行一鍋化的反應，三級膦會優先攻打三鍵上的alpha位，之後進行環化反應，形成gamma-內醯胺的化合物，經過氫譜、碳譜、磷譜、紅外線光譜、質譜和單晶繞射的鑑定，則可驗證出此結構帶有Ylide結構，並在藉由三級膦與雙炔和醛類的反應更加證明此反應機構的推導。因為此產物帶有Ylide結構，所以可以進行Wittig反應，在日後全合成上必有一些幫助。
　　另一方面，利用碳七十對其開洞到20員環的過程，來探討跟碳六十開洞一些不一樣的地方，並藉由12員環異構物的單晶繞射來探討其機構，之後將碳七十擴環到20員環，利用變溫NMR實驗來看洞裡的含水量有何變化，並藉由紫外可見光光譜和循環伏安法計算出碳七十20員環的HOMO和LUMO，並與PCBM和ICBA做比較。

Antiretroviral drug have been developed in recent years and some antiretroviral drugs are commercial available. For example, Amprenavir and Indinavir are some of these commercial available drugs. Issues of some side effects and the cost for production of these antiretroviral drug have been primary concerns. Highly-efficient and low-cost synthetic procedures for drug syntheses can be conducive to human. Some gamma-lactam antiretroviral drugs have been reported, such as gamma-lactam-like Amprenavir and Indinavir. Because these drugs are gamma-lactam derivatives, we are interested in developing a one-pot synthetic method to its synthetic precursors. In this study, we used phosphine, (E)-dimethyl hex-2-en-4-ynedioate and N-Benzylidene-p-toluenesulfonamide to obtain the gamma-lactam intermediates bearing ylide functionality. We characterized these products by 1H, 13C, 31P, IR, Mass and X-ray diffraction analyses. These readily available structures may be adventageous to the total synthesis of molecules having lactam moiety.
The other study, we synthesized the 12-member ring of [70]fullerene and we also studied the isomers about the open-cage products. Form the reference of Iwamatsu, we can use 1,2-Diaminobenzene to enlarge 12-member ring of [70]fullerene to 20-member ring. We can find the water in the 20-member ring product by 1H NMR. Because water can go inside the 20-member ring spontaneous, we did the variable temperature NMR experiment to see that the ratio of water inside when change the temperature. Finally, we characterized the HOMO, LUMO and band gap of 20-member ring and compare with the PCBM and ICBA.

摘要 i
Abstract ii
目錄 iv
圖目錄 viii
表目錄 xiii
第一章 緒論 1
1.1 多組成反應 1
1.1.1 多組成反應的由來 1
1.1.2 多組成反應的歷史 1
1.1.3 多組成反應的定義及種類 4
1.1.4 多組成反應的應用 5
1.1.4.1 Mannich反應 5
1.1.4.2 自由基的多組成反應 6
1.1.4.3 有機硼多組成反應 7
1.1.4.4 金屬催化多組成反應 9
1.1.5 雜環化合物的多組成反應 9
1.1.5.1 兩性離子的產生 9
1.1.5.2 g-丁內酯的多組成反應 10
1.1.5.3 g-內醯胺的多組成反應 12
1.1.5.4 呋喃的多組成反應 14
1.1.5.5 吡咯的多組成反應 15
1.1.5.6 其他異環化合物的多組成反應 16
1.1.5.7 不對稱炔類的多組成反應 17
1.1.5.8 烯炔的多組成反應 18
1.1.6 多組成反應的發展與未來展望 19
1.1.6.1 多組成反應的優點與環境影響 19
1.1.6.2 多組成反應在藥物上應用 20
1.2 人類免疫缺陷病毒（HIV） 20
1.2.1人類免疫缺陷病毒簡介 20
1.2.2 強效抗愛滋療法（highly active anti-retroviral therapy, HAART）21
1.2.3 蛋白酶抑制劑（PI） 21
1.2.3.1 蛋白酶抑制劑的種類 21
1.2.3.2 g-內醯胺的HIV-1蛋白酶抑制劑 22
1.3 碳六十和碳七十的開洞合成 23
1.3.1 碳六十和碳七十的發展 23
1.3.2 碳六十的開洞發展 24
1.3.2.1 球外修飾與球內修飾 24
1.3.2.2 擴張碳六十開洞環張數 25
1.3.2.3 現階段的開洞發展 26
1.3.2.4 將塞氫氣的開洞碳六十關起來 30
1.3.2.5 碳七十的開洞與關洞 31
1.3.3 碳六十開洞之未來發展 31
第二章 非催化之三級膦反應 33
2.1 研究動機 33
2.2 烯炔、亞胺與三級膦的多組成反應 33
2.2.1 烯炔的合成 33
2.2.2 亞胺的合成 35
2.2.3 1a反應條件的尋找 36
2.2.4 改變三級膦和亞胺的官能基的反應探討 38
2.2.5雙稀的產生 42
2.2.6 產物5的鑑定 43
2.2.6.1 產物5a氫譜的鑑定 43
2.2.6.2 產物5a磷譜的鑑定 44
2.2.6.3 產物5a碳譜的鑑定 45
2.2.6.4 產物5a紅外線光譜、質譜和X-ray的鑑定 48
2.2.7 產物5反應機構的推導 50
2.3 雙炔、醛類和三級膦的多組成反應 51
2.3.1 雙炔的合成 51
2.3.2 1b反應條件的尋找 52
2.3.3改變三級膦和醛類官能基的反應探討 54
2.3.4 產物6的鑑定 56
2.3.4.1 產物6a氫譜的鑑定 56
2.3.4.2 產物6a磷譜的鑑定 57
2.3.4.3 產物6a碳譜的鑑定 58
2.3.4.4 產物6a 紅外線光譜和質譜的鑑定 60
2.3.4 產物6的反應機構推導 61
2.3.5 產物7的探討 62
第三章 富勒烯開洞之研究 73
3.1 研究動機 73
3.2 碳七十12員環的探討 73
3.3 碳七十20員環的探討 78
3.3.1 產物的合成 78
3.3.2 產物14的探討 82
3.3.2.1 產物14的紅外線光譜 82
3.3.2.1 產物14的紫外可見光光譜和電化學 83
第四章 結論 86
參考文獻 87

[1] Woodward, R.B.; Cava, M.P.; Ollis, W.D.; Hunger, A.; Daeniker, H.U.; Schenker, K. J. Am. Chem. Soc. 1954, 76, 4749–4751.
[2] Knight, S.; Overman, L.; Pairaudeau, G. J. Am. Chem. Soc. 1993, 115, 9293–9294.
[3] Magnus, P.; Giles, M.; Bonnert, R.; Johnson, G.; McQuire, L.; Deluca, M.; Merritt, A.; Kim, C. S.; Vicker, N. J. Am. Chem. Soc. 1992, 114, 4403–4405.
[4] Kuehne, M. E.; Xu, F. J. Org. Chem. 1993, 58, 7490–7497.
[5] Rawal, V. H.; Iwasa, S. J. Org. Chem. 1994, 59, 2685–2686.
[6] Strecker, A. Liebigs Ann. Chem. 1850, 75, 27–45.
[7] Robinson, R. J. Chem. Soc. 1917, 111, 762–768.
[8] Humphrey, A. J.; OʼHagan, D. Nat. Prod. Rep. 2001, 18, 494–502.
[9] Passerini, M.; Simone, L. Gazz. Chim. Ital. 1921, 51, 126–129.
[10] Ugi, I. Angew. Chem. Int. Ed. Engl. 1962, 1, 8–20.
[11] Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. Engl. 2000, 39, 3168–3210.
[12] Ugi, I. Molecules. 2003, 8, 53–66.
[13] Mannich, C.; Krosche, W. Arch. Pharm. 1912, 250, 647–667.
[14] Bur, S. K.; Martin, S. F. Tetrahedron. 2001, 57, 3221–3242.
[15] Tsuchii, K.; Doi, M.; Hirao, T.; Ogawa, A. Angew. Chem. Int. Ed. Engl. 2003, 42, 3490–3493.
[16] Heaney, H, Compreh. Org. Synth. 1991, 4, 953–973.
[17] Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc. 1997, 119, 445–446.
[18] Chen, C.-P.; Luo, C.; Ting, C.; Chuang, S.-C. Chem. Commun. 2010, 1, 1–3.
[19] Gevorgyan, V.; Radhakrishnan, U.; Takeda, a; Rubina, M.; Rubin, M.; Yamamoto, Y. J. Org. Chem. 2001, 66, 2835–2841.
[20] Winterfeldt, E. Angew. Chem. 1967, 6, 423–434.
[21] Ziyaei-Halimehjani, A.; Saidi, M. R. Tetrahedron Lett. 2008, 49, 1244–1248.
[22] Li, C. Q.; Shi, M. Org. Lett. 2003, 5, 4273–4276.
[23] Nair, V.; Bindu, S.; Sreekumar, V.; Rath, N. P. Org. Lett. 2003, 5, 665–667.
[24] Kazmierski, W. M.; Andrews, W.; Furfine, E.; Spaltenstein, A.; Wright, L. Bioorg. Med. Chem. Lett. 2004, 14, 5689–5692.
[25] Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031–5041.
[26] Trost, B. M.; Marrs, C. M. J. Am. Chem. Soc. 1993, 115, 6636–6645.
[27] Wei, J.; Shaw, J. T. Org. Lett. 2007, 9, 4077–4080.
[28] Ma, C.; Ding, H.; Zhang, Y.; Bian, M. Angew. Chem. Int. Ed. Engl. 2006, 45, 7793–7797.
[29] Anary-Abbasinejad, M.; Charkhati, K.; Anaraki-Ardakani, H. Synlett. 2009, 1115–1117.
[30] Zhang, H.; Yang, G.; Chen, J.; Chen, Z. Synlett, 2004, 3055–3059.
[31] Sasada, T.; Kobayashi, F.; Sakai, N.; Konakahara, T. Org. Lett., 2009, 11, 2161–2164.
[32] Adib, M.; Ansari, S.; Feizi, S.; Damavandi, J. A.; Mirzaei, P. Synlett, 2009, 3263–3266.
[33] Cao, H.; Wang, X.; Jiang, H.; Zhu, Q.; Zhang, M.; Liu, H. Chem. Eur. J. 2008, 14, 11623–11633.
[34] Zhang, M.; Jiang, H. F.; Liu, H. L.; Zhu, Q. H. Org. Lett. 2007, 9,4111.
[35] Chuang, S.-C.; Santhosh, K. C.; Lin, C.-H.; Wang, S. L.; Cheng, C. H. J. Org. Chem. 1999, 64, 6664–6669.
[36] Azizi, N.; Torkiyan, L.; Saidi, M. R. Org. Lett., 2006, 8, 2079–2082.
[37] Passerini, M.; Simone, L.; Gazz. Chim. Ital. 1921, 51, 126.
[38] Moran, E. J.; Tellew, J. E.; Zhao, Z.; Armstrong, R. W.. J. Org. Chem.1993, 58, 7848–7859.
[39] Salturo, F.; Baker, C.; Court, J.; Deiningr, D.; Kim, E.; Li, B.; Novak, P.; Rao, B.; Pazhanisamy, S.; Porter, M. Bioorg. Med. Chem. Lett. 1998, 8, 3637–3642.
[40] (1) Spaltenstein, A.; Almond, M. R.; Bock, W. J.; Cleary, D. G.; Furfine, E. S.; Hazen, R. J.; Kazmierski, W. M.; Salituro, F. G.; Tung, R. D.; Wright, L. L. Bioorg. Med. Chem. Lett. 2000, 10, 1159–1162. (2) Kazmierski, W. M.; Andrews, W.; Furfine, E.; Spaltenstein, A.; Wright, L. Bioorg. Med. Chem. Lett. 2004, 14, 5689–5692.
[41] Osawa, E. Kagaku. 1970, 25, 854–863.
[42] Rohlfing, E. A.; Cox, D. M.; Kaldor, A. J. Chem. Phys. 1984, 81, 3322–3330.
[43] Kroto, H. W.; H., J. R.; O'Brien, S. C.; Curl, R. F.; Smalley, R. E. Nature. 1985, 318, 162–163.
[44] Cekovic, Z. Hemijski Pregled. 1997, 38, 34–35.
[45] Kratschmer, W.; Lamb, L.D.; Fostiropoulos, K.; Huffman, D. R. Nature. 1990, 347, 354–358.
[46] Hummelen, J. C.; Knight, B. W.; LePeq, F.; Wudl, F.; Yao, J.;Huang, J.; Wilkins, C. L. J. Org. Chem. 1995, 60, 532–538.
[47] Hummelen, J. C.; Prato, M.; Wudl, F. J. Am. Chem. Soc. 1995, 117, 7003–7004.
[48] (a) Arce, M.-J.; Viado, A. L.; An, Y.-Z.; Khan, S. I.; Rubin, Y. J. Am. Chem. Soc. 1996, 118, 3775–3776. (b) Edwards, C. M.; Butler, I. S.; Qian, W.; Rubin, Y. J. Mol. Struct. 1998, 442, 169–174.
[49] Rubin, Y.; Jarrosson, T.; Wang, G.-W.; Bartberger, M. D.; Houk, K. N.; Schick, G.; Saunders, M.; Cross, R. J. Angew. Chem. Int. Ed. Engl. 2001, 40, 1543–1546.
[50] Murata, Y.; Kato, N.; Komatsu, K., J. Org. Chem. 2001, 66, 7235–7239.
[51] Inoue, H.; Yamaguchi, H.; Iwamatsu, S.; Uozaki, T.; Suzuki, T.; Akasaka, T.; Nagase, S.; Murata, S. Tetrahedron Lett. 2001, 42, 895–897.
[52] Murata, Y.; Murata, M.; Komatsu, K. Chem. Eur. J. 2003, 9, 1600–1609.
[53] Iwamatsu, S.; Ono, F.; Murata, S. Chem. Commun. 2003, 1268–1269.
[54] Iwamatsu, S.; Uozaki, T.; Kobayashi, K.; Re, S.; Nagase, S.; Murata, S. J. Am. Chem. Soc. 2004, 126, 2668–2669.
[55] Komatsu, K.; Murata, M.; Murata, Y. Science. 2005, 307, 238–240.
[56] Stanisky, C. M.; Cross, R. J.; Saunders, M. J. Am. Chem. Soc. 2009, 131, 3392–3395.
[57] Iwamatsu, S.; Stanisky, C. M.; Cross, R. J.; Saunders, M.; Mizorogi, N.; Nagase, S.; Murata, S. Angew. Chem., Int. Ed. 2006, 45, 5337–5340.
[58] Whitener, K. E.; Frunzi, M.; Iwamatsu, S.; Murata, S.; Cross, R. J.; Saunders, M. J. Am. Chem. Soc. 2008, 130, 13996–13999.
[59] Whitener, K. E.; Cross, R. J.; Saunders, M.; Iwamatsu, S.; Murata, S.; Mizorogi, N.; Nagase, S. J. Am. Chem. Soc. 2009, 131, 6338–6339.
[60] Murata, M.; Maeda, S.; Morinaka, Y.; Murata, Y.; Komatsu, K. J. Am. Chem. Soc. 2008, 130, 15800–15801.
[61] Wenkert, E.; Adams, K.; Leicht, C. L. Can. J. Chem. 1963, 41, 1844–1846.
[62] Dai, M.; Sarlah, D.; Yu, M.; Danishefsky, S. J.; Jones, G. O.; Houk, K. N. J. Am. Chem. Soc. 2007, 129, 645–657.
[63] Sharghi, H.; Hosseini-Sarvari, M.; Ebrahimpourmoghaddam, S. ARKIVOC. 2007, 15, 255–264.
[64] Zhou, L. H.; Yu, X. Q.; Pu, L. Tetrahedron Lett. 2010, 51, 425–427.
[65] Boisvert, L.; Beaumier, F.; Spino, C. Org. Lett. 2007, 9, 5361–5363.
[66] (1) Lange's Handbook of Chemistry, 10th ed. 1496. (2) CRC Handbook of Chemistry and Physics, 44th ed. 2143.
[67] Wozacuteniak, L. Tetrahedron Lett. 1999, 40, 2637–2640.
[68] Hay, A. S. J. Org. Chem. 1962, 27, 3320–3321.
[69] Cox, D. M.; Behal, S.; Disko, M.; Gorun, S. M.; Greaney, M.; Hsu, C. S.; Kollin, E. B.; Millar, J.; Robbins, J. J. Am. Chem. Soc. 1991, 113, 2940–2944.
[70] Cheng, Y. J.; Hsieh, C. H.; He, Y.; Hsu, C. S.; Li, Y. J. Am. Chem. Soc. 2010, 132, 17381–17383.