Total Synthesis of Pikrosalvin, Simplexene C, D and Synthetic Studies toward Swartziarboreol G and Simplexene B

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：10

、訪客IP：18.188.40.207

姓名

黃柔潔(Rou-Jie Huang) 查詢紙本館藏

畢業系所

化學學系

論文名稱

(Total Synthesis of Pikrosalvin, Simplexene C, D and Synthetic Studies toward Swartziarboreol G and Simplexene B)

相關論文

★ 以手性有機硫催化劑進行不對稱環丙烷化反應並應用於合成吡咯類化合物之研究

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 ( 永不開放)

摘要(中)

本論文敘述Simplexene C, D和Pikrosalvin 之全合成，以及Swartziarboreol G和Simplexene B之合成研究。Swartziarboreol G and Simplexene B, C, D為一種新發現具有抗白色念珠菌活性的cassane類型的二萜類化合物，另一種結構非常類似的天然物Pikrosalvin為1962年從鼠尾草葉子中分離出來，尚未進行任何活性測試。合成上，我們以香草酸 (vanillic acid) 為起始物，先進行官能基的轉換、保護，經由親電芳香取代引入三甲基矽 (TMS) 基團以及ㄧ鍋化 (one-pot) 反應一步製備出二烯化合物，再利用實驗室所新開發的多烯環化方法建立反式十氫萘核心骨架，接著將三甲基矽基團置換成碘化物以進行Suzuki 耦合反應得到苯乙烯，然後經由氧化內酯化反應得到甲基內酯 (methyl lactone) 再將甲基芳基醚水解去甲基完成Pikrosalvin之全合成，另外，以同樣的苯乙烯中間體進行氧化內酯化建立羥基內酯 (hydroxy lactone)，接著將保護基移除後以高效液相層析法掌性分離管柱 (chiral HPLC column) 分離異構物，完成Simplexene C之全合成，最後再對其中一個異構物進行甲基芳基醚水解去甲基即可得到天然物Simplexene D。
　　本論文合成重點為利用本實驗室所開發的多烯環化反應方法，將其應用在天然物Simplexene B, C, D、Swartziarboreol G和Pikrosalvin 之全合成研究上，以增加其應用性。

摘要(英)

The new anti-Candida cassane-type diterpenes Swartziarboreol G and Simplexene B, C, D were isolated from the root bark of Panamanian plant Swartzia simplex by Queiroz et al. in 2015. These secondary metabolites exhibited a strong antifungal activity against Candida albicans. Another natural product Pikrosalvin was isolated from the leaf of Salvia officinalis in 1962 with similar structure to Swartziarboreol G and Simplexene B, C, D. The need for further biological investigations prompted us to conduct the synthetic studies.
A number of polyene cyclization methods have been reported for the total synthesis of 　polycyclic natural products. We applied a new polyene cyclization method, which was developed by our group as a key step for the total synthesis of these natural products. So far, we have finished the total synthesis of Pikrosalvin, Simplexene C and Simplexene D.

關鍵字(中)

★ 天然物全合成
★ 多烯環化反應

關鍵字(英)

★ total synthesis of natural products
★ polyene cyclization
★ cassane-type diterpenes

論文目次

目錄

中文摘要····································································································i
Abstract·····································································································ii
誌謝········································································································iii
目錄·········································································································iv
圖目錄······································································································vi
表目錄······································································································ix
符號說明···································································································x
第一章：緒論·······························································································1
　　　1-1 天然物Simplexene B, C, D和Swartziarboreol G之單離與生物活性·············1
　　　1-2 天然物Pikrosalvin之單離·································································3
　　　1-3 Cassane類天然物之全合成文獻回顧···················································4
　　　1-4 多烯環化反應(polyene cyclization)·····················································5
　　　　　1-4-1 生物合成途徑······································································5
　　　　　1-4-2 仿生合成方法······································································6
　　　1-5 研究動機·····················································································7
第二章：結果與討論······················································································9
　　　2-1 Pikrosalvin, Simplexene B, C, D和Swartziarboreol G之逆合成分析··············9
　　　　　2-1-1 逆合成分析一······································································9
　　　　　2-1-2 逆合成分析二·····································································10
　　　2-2 二烯化合物的製備·······································································11
　　　　　2-2-1 合成路徑一········································································11
　　　　　2-2-2 合成路徑二········································································18
　　　2-3 多烯環化反應建立反式十氫萘核心結構············································22
　　　2-4 苯環上雙鍵取代的建立·································································30
　　　　　2-4-1 Vilsmeier-Haack反應建立醛類後進行Wittig olefination··················30
　　　　　2-4-2將三甲基矽基團置換成碘化物後建立醛類再進行Wittig olefination···31
　　　　　2-4-3利用碘化物進行耦合反應·······················································36
　　　2-5 Pikrosalvin之全合成······································································41
　　　2-6 Simplexene C, D之全合成·······························································44
　　　2-7 Simplexene B和Swartziarboreol G之合成研究······································49
　　　2-8不對稱合成、其他合成路徑之嘗試····················································51
　　　　　2-8-1不對稱合成C15之掌性中心····················································51
　　　　　2-8-2其他合成策略、結果討論·························································54
　　　2-9 天然物Pikrosalvin之萃取分離·························································58
第三章：結論·····························································································59
第四章：實驗部分·······················································································60
　　　4-1 General Method·············································································60
　　　4-2 Experimental Procedures and Spectra Data·············································61
參考文獻··································································································85
附錄········································································································87

參考文獻

[1] Favre-Godal, Q.; Dorsaz, S.; Queiroz, E. F.; Marcourt, L.; Ebrahimi, S. N.; Allard, P.-M.; Voinesco, F.; Hamburger, M.; Gupta, M. P.; Gindro, K.; Sanglard, D.; Wolfender, J.-L. J. Nat. Prod. 2015, 78, 2994-3004.
[2] Schultes, R. E. J. Ethnopharmacol. 1979, 1, 79-87.
[3] CYTED. Plantas Medicinales Iberoamericanas; Edición de la Organizacion Del Convenio Andrés Bello: Bogota, 2008; p 1003.
[4] Brieskorn, C. H. Chem. Ber. 1962, 95, 3034-3041.
[5] Qiao, Y.; Xu, Q.; Hu, Z.; Li, X.-N.; Xiang, M.; Liu, J.; Huang, J.; Zhu, H.; Wang, J.; Luo, Z.; Xue, Y.; Zhang, Y. J. Nat. Prod. 2016, 79, 3134-3142.
[6] Mahdjour, S.; Harche-Kaid, M.; Haidour, A.; Chahboun, R.; Alvarez-Manzaneda, E. Org. Lett. 2016, 18, 5964-5967.
[7] Stork, G.; Burgstahler, A. W. J. Am. Chem. Soc. 1955, 77, 5068-5077.
[8] Eschenmoser, A.; Ruzicka, L.; Jeger, O.; Arigoni, D. Helv. Chim. Acta. 1955, 38, 222-230
[9] Yoder, R. A.; Johnston, J. N. Chem. Rev. 2005, 105, 4730-4756.
[10] Corey, E. J.; Cheng, H.; Baker, C. H.; Matsuda, S. P. T.; Li, D.; Song, X. J. Am. Chem. Soc. 1997, 119, 1289-1296.
[11] Corey, E. J.; Virgil, S. C.; Cheng, H.; Baker, C. H.; Matsuda, S. P. T.; Singh, V.; Sarshar, S. J. Am. Chem. Soc. 1995, 117, 11819-11820.
[12] Wendt, K.U.; Schulz, G.E.; Corey, E.J.; Liu, D.R. Angew. Chem. Int. Ed. 2000, 39, 2812-2833.
[13] Ishihara, K.; Nakamura, S.; Yamamoto, H. J. Am. Chem. Soc. 1999, 121, 4906-4907.
[14] Lin, S.-C.; Chein, R.-J. J. Org. Chem. 2017, 82, 1575-1583.
[15] de Silva, S. O.; Reed, J. N.; Billedeau, R. J.; Wang, X.; Norris, D. J.; Snieckus, V. Tetrahedron 1992, 48, 4863-4878.
[16] Fache, F.; Suzan, N.; Piva, O. Tetrahedron 2005, 61, 5261-5266.
[17] Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521-2522.
[18] Liang, H.; Hu, L.; Corey, E. J. Org. Lett. 2011, 13, 4120-4123.
[19] Kumar Sharma, A.; Maheshwary, Y.; Singh, P.; Singh, K ARKIVOC 2010, 9, 54-62.
[20] Mills, R. J.; Taylor, N. J.; Snieckus, V. J. Org. Chem. 1989, 54, 4372-4385.
[21] Jørgensen, K. B.; Rantanen, T.; Dörfler, T.; Snieckus, V. J. Org. Chem. 2015, 80, 9410-9424.
[22] Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581-584.
[23] Tada, M.; Kurabe, J.; Yasue, H.; Ikuta, T. Chem. Pharm. Bull. 2008, 56, 287-291.
[24] Godeau, J.; Olivero, S.; Antoniotti, S.; Duñach, E. Org. Lett. 2011, 13, 3320-3323.
[25] Lin, Y. C.; Chen, C. T. Chem. Eur. J 2012, 19, 2531-2538.
[26] Fresneau, N.; Dumas, N.; Tournier, B. B.; Fossey, C.; Ballandonne, C.; Lesnard, A.; Millet, P.; Charnay, Y.; Cailly, T.; Bouillon, J.-P.; Fabis, F. Eur. J. Med. Chem. 2015, 94, 386-396.
[27] Kauch, M.; Hoppe, D. Synthesis 2006, 2006, 1578-1589.
[28] Takami, K.; Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1997-1999.
[29] Grirrane, A.; Garcia, H.; Corma, A. J. Catal. 2013, 302, 49-57.
[30] Bhalla, V.; Singh, H.; Kumar, M. Org. Lett. 2010, 12, 628-631.
[31] Sanaboina, C.; Chidara, S.; Jana, S.; Eppakayala, L. Tetrahedron Lett. 2016, 57, 1767-1770.
[32] Mikula, H.; Hametner, C.; Fröhlich, J. Synth. Commun. 2013, 43, 1939-1946.
[33] Keck, G. E.; McLaws, M. D.; Wager, T. T. Tetrahedron 2000, 56, 9875-9883.
[34] Mamidyala, S. K.; Ramu, S.; Huang, J. X.; Robertson, A. A. B.; Cooper, M. A. Bioorg. Med. Chem. Lett. 2013, 23, 1667-1670.
[35] Kang, Y.-B.; Gade, L. H. J. Org. Chem. 2012, 77, 1610-1615.
[36] Novoa, M. L.; Escalante, Y.; Maldonado, L.; Galindo-Castro, I.; Álvarez, A.; Figarella, K.; Marsiccobetre, S.; Arocha, I.; Nieves, J.; Salazar, F.; Gámez, C.; Canudas, N.; Tropper, E.; González, T.; Villamizar, J. E. Nat. Prod. Res. 2015, 29, 207-212.
[37] Haas, D.; Hofmayer, M. S.; Bresser, T.; Knochel, P. Chem. Commun. 2015, 51, 6415-6417.

指導教授

陳榮傑謝發坤(Rong-Jie Chein Fa-Kuen Shieh)

審核日期

2018-7-17

推文