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博碩士論文 etd-0911112-174722 詳細資訊
Title page for etd-0911112-174722
論文名稱
Title
肉質軟珊瑚Sarcophyton ehrenbergi所含二次代謝物之研究
Studies on the Secondary Metabolites from the Formosan Soft Coral Sarcophyton ehrenbergi
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
235
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2012-08-21
繳交日期
Date of Submission
2012-09-11
關鍵字
Keywords
細胞毒殺、抗人類巨細胞病毒、雙萜類、肉質軟珊瑚、三仙台
anti-HCMV, diterpene, San-Hsien-Tai, cytotoxicity, Sarcophyton ehrenbergi
統計
Statistics
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中文摘要
為了從海洋生物體尋找具有生物活性的二次代謝物,本研究針對台東三仙台海域所採集到的肉質軟珊瑚Sarcophyton ehrenbergi進行化學成分之研究。從軟珊瑚S. ehrenbergi有機萃取物中分離得到九個新的雙萜類cembrane化合物1–9以及一個首次天然分離之雙萜類cembrane化合物10。這些純化合物之化學結構鑑定,主要是透過其有機光譜的分析(一維與二維核磁共振圖譜、質譜、紫外線光譜、紅外線光譜)以及比對已知化合物之文獻光譜資料而決定。
此外,化合物 1–10 分別對於人類肺癌細胞(A-549)、人類直腸癌細胞(HT-29)與老鼠血癌細胞 (P-388)進行細胞毒殺活性實驗,以及抗人類巨細胞病毒 (human cytomegalovirus) 測試,結果發現化合物3、6、9和10對P-388皆有毒殺活性,其ED50 值分別為2.7、3.6、2.0和3.0 μg/mL,而化合物1、2、3和7則對人類巨細胞病毒有抑制活性,EC50 值分別為60、46、5和45 μg/mL。
Abstract
In the course of studying on secondary metabolites from marine organisms, we have investigated the chemical constituents of the soft coral Sarcophyton ehrenbergi collected at San-Hsien-Tai, Taitong County, Taiwan. Chromatographic separation of the organic extracts has led to the isolation of nine new cembrane diterpenes 1–9, and a initial natural separation of known cembrane diterpene 10. The chemical structures of pure compounds were determined by spectral (NMR, MS, UV and IR) and physical data, as well as comparison with the spectroscopic data of related chemicals in literature.
Moreover, the metabolites 1–10 were evaluated in vitro for their cytotoxicity against of A-549 (human lung epithelial carcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cells, as well as anti-HCMV activity. Compounds 3, 6, 9, and 10 were shown to exhibit significant cytotoxicity activities against P-388 with ED50 values of 2.7, 3.6, 2.0, and 3.0 μg/mL, respectively. Compound 1, 2, 3, and 7 exhibited inhibitory activity against anti-HCMV, with EC50 values of 60.0, 46.0, 5.0, and 45.0 μg/mL.
目次 Table of Contents
論文審定書 i
謝辭 ii
中文摘要 iii
英文摘要 iv
化合物 1–10 之化學結構 v
目錄 vi
表次 viii
圖次 ix
縮寫對照表 xv
壹、緒論 1
貳、軟珊瑚Sarcophyton ehrenbergi文獻回顧 2
一、軟珊瑚Sarcophyton ehrenbergi之分類地位 2
二、軟珊瑚Sarcophyton ehrenbergi之二次代謝物文獻回顧 3
1. Cembrane類之骨架化合物 4
2. Cadinane類之骨架化合物 14
3. Guaiane類之骨架化合物 16
4. Ceramide類化合物 18
5. Cerebroside類化合物 19
6. Trinor tetraterpene類化合物 22
參、材料及研究方法 23
一、實驗設備儀器 23
二、實驗材料 25
三、軟珊瑚Sarcophyton ehrenbergi 樣品採集 26
四、軟珊瑚Sarcophyton ehrenbergi 之萃取與分離流程 27
五、軟珊瑚Sarcophyton ehrenbergi 之分離純化 29
1. SST13-14-C-L100-70-65-18 (1) 之分離純化 29
2. SST13-15-41-8 (2) 之分離純化 30
3. SST13-14-b-L41-90-85-6-H11 (3) 之分離純化 31
4. SST13-19-50-22 (4) 之分離純化 32
5. SST13-17-g-80-75-15-4 (5) 之分離純化 33
6. SST13-14-b-L41-90-85-4 (6) 之分離純化 34
7. SST13-16-f-60-65-11 (7) 之分離純化 35
8. SST13-16-c-70-7 (8) 之分離純化 36
9. SST13-16-g-70-e-70-11-31 (9) 之分離純化 37
10. SST13-14-d-90-85-18 (10) 之分離純化 38
肆、化學成分之結構解析 39
一、SST13-14-C-L100-70-65-18 (1) 之結構解析 39
二、SST13-15-41-8 (2) 之結構解析 58
三、SST13-14-b-L41-90-85-6-H11 (3) 之結構解析 76
四、SST13-19-50-22 (4) 之結構解析 93
五、SST13-17-g-80-75-15-4 (5) 之結構解析 111
六、SST13-14-b-L41-90-85-4 (6) 之結構解析 128
七、SST13-16-f-60-65-11 (7) 之結構解析 145
八、SST13-16-c-70-7 (8) 之結構解析 162
九、SST13-16-g-70-e-70-11-31 (9) 之結構解析 181
十、SST13-14-d-90-85-18 (10) 之結構判定 200
伍、生物活性測試之分析方法 207
一、細胞毒殺活性測試 207
二、MTT分析原理 207
三、細胞毒殺活性試驗結果 208
四、抗 HCMV 病毒的測試 210
陸、結論 211
柒、參考文獻 213
參考文獻 References
1. 法蘭克.薛慶(Frank Schätzing)作;丁君君、劉永強譯, Nachrichten Aus Einen Unbekannten Universum Eine Zeitreise durch die Meere;海,另一個未知的宇宙,
野人出版,台北,中華民國,2008,365–370。
2. 邵廣昭,台灣本土物種全都錄–45,000 種本土物種可上網查閱,行政院國家科學委員會之專題報導,2005/4/7。
3. 方力行,珊瑚學–間論台灣的珊瑚資源,黎明文化出版,台北,中華民國,1989,71–84。
4. (a) 何立德、王鑫、戴昌鳳,臺灣的珊瑚礁,遠足文化出版,台北,中華民國,2002,74–76。
(b) 戴昌鳳,台灣珊瑚礁地圖–台灣本島篇(上)、離島篇(下),天下遠見出版,台北,中華民國,2011。
5. Bowden, B. F.; Coil, J. C.; Hicks, W.; Kazlauskas, R.; Mitchell, S. J., Studies of Australian Soft Corals. X* The Isolation of Epoxyisoneocembrene-A from Sinularia grayi and Isoneocembrene-A from Sarcophyton ehrenbergi. Aust. J. Chem. 1978, 31, 2707-2712.
6. Konig, G. M.; Wright, A. D., New Cembranoid Diterpenes from the Soft Coral Sarcophyton ehrenbergi. J. Nat. Prod. 1998, 61, 494-496.
7. Cheng, S.-Y.; Wang, S.-K.; Chiou, S.-F.; Hsu, C.-H.; Dai, C.-F.; Chiang, M. Y.; Duh, C.-Y., Cembranoids from the Octocoral Sarcophyton ehrenbergi. J. Nat. Prod. 2010, 73, 197-203.
8. Shaker, K. H.; Muller, M.; Ghani, M. A.; Dahse, H.-M.; Seifert, K., Terpenes from the Soft Corals Litophyton arboreum and Sarcophyton ehrenbergi. Chem. Biodivers. 2010, 7, 2007-2015.
9. Cheng, S.-Y.; Wen, Z.-H.; Chiou, S.-F.; Tsai, C.-W.; Wang, S.-K.; Hsu, C.-H.; Dai, C.-F.; Chiang, M. Y.; Wang, W.-H.; Duh, C.-Y., Ceramide and Cerebrosides from the Octocoral Sarcophyton ehrenbergi. J. Nat. Prod. 2009, 72, 465–468.
10. Dauben W. G.; Thiessen W. E.; Resnick P. R., Cembrene, A 14-Membered Ring Diterpene Hydrocarbon, 1962, 84, 2014–2015.
11. Hiroshi K.; Saburo A., Terpenoids. VI. The Structure of Thunbergene 1963, 36, 823–826.
12. Torssell, K., Natural Product Chemistry, A Mechanistic, Biosynthetic and Ecological Approch. 2nd ed.; Swedish Pharmaceutical Press,Sweden: 1997.
13. Bowden, B. F.; Coil, J. C.; Heaton, A.; König, G.; Bruck, M. A.; Cramer, R. E.; Klein, D. M.; Scheuer, P. J., The Structures of Four Isomeric Dihydrofuran-Containing Cembranoid Diterpenes from Several Species of Soft Coral. J. Nat. Prod. 1987, 50, 650-659.
14. Kobayashi M.; Nakagawa T,; Mitsuhashi H., Marine Terpenes and Terpenoids. I. Structures of Four Cembrane-Type Diterpenes; Sarcophytol-A, Sarcophytola Acetate Sarcophytol-B, and Sarcophytonin-A, From the Soft Coral, Sarcophyton glaucum Chem. Phurm. Bull., 1979, 27, 2382-2387.
15. Herin, M.; Tursch, B., Chemical Studies of Marine Invertebrates. XXIV. Minor Cembrane Diterpenes from the Soft Coral Sinularia flexibilis (Coelenterata, Octocorallia) Bull. Soc. Chim. Belg., 1976, 85, 707-719.
16. Yamada, K.; Ryu, K.; Miyamoto, T.; Higuchi, R., Bioactive Terpenoids from Octocorallia. 4. Three New Cembrane-Type Diterpenoids from the Soft Coral Lobophytum schoedei. J. Nat. Prod. 1997, 60, 798-801.
17. Bernstein, J.; Shmeuli, U.; Zadock, E.; Kashman, Y., Sarcophine, a New Epoxy cembranolide from Marine Origin. Tetrahedron 1974, 30, 2817-2824.
18. Bowden, B. F.; Coll, J. C.; Mitchell, S. J., Studies of Australian Soft Corals. XVIII* Further Cembranoid Diterpenes from Soft Corals of the Genus Sarcophyton. Aust. J. Cherm. 1980, 33, 879-884.
19. Gross, H.; Wright, A. D.; Beil, W.; Konig, G. M., Two New Bicyclic Cembranolides from a New Sarcophyton species and Determination of the Absolute Configuration of Sarcoglaucol-16-one. Org. Biomol. Chem. 2004, 2, 1133-1138.
20. Kashman, Y.; Zadock, E.; Nbeman, I., Some New Cembrane Derivatives of Marine Origin. Tetrahedron 1974, 30, 3615-3620.
21. Bowden, B. F.; Coll, J. C.; Mitchell, S. J.; Stokie, G. J., Studies of Australian Soft Corals. XI* Two New Cembranoid Diterpenes from a Sarcophyton Species. Aust. J. Chem. 1979, 32, 653-659.
22. Shin, J.; Fenical, W., New Cembradiene Diterpenoids from an Undescribed Caribbean Gorgonian of the Genus Eunicea. Tetrahedron 1993, 49, 515-524.
23. Greenland, G. J.; Bowden, B. F., Cembranoid Diterpenes Related to Sarcophytol A from the Soft Coral Sarcophyton trocheliophorum (Alcyonacea). Aust. J. Chem. 1994, 47, 2013-2021.
24. Yin, S.-W.; Shi, Y.-P.; Li, X.-M.; Wang B. G., A New Cembranoid Diterpene and Other Related Metabolites from the South-China-Sea Soft Coral Lobophytum crassum. Helv. Chim. Acta 2006, 89, 567-572.
25. Chen, S. H.; Huang, H.; Guo, Y. W., A New Diterpenoid from the South China Sea Soft Coral Lobophytum sp. J. Nat. Prod. Reser. 2008, 10, 965-969.
26. Vanderah, D. J.; Rutledge, N.; Schmitz, F. J.; Ciereszko, L. S., Marine Natural Products: Cembrene-A and Cembrene-C from a Soft Coral, Nephthea sp. J. Org. Chem. 1978, 43, 1614-1616.
27. Kashman, Y.; Carmely, S.; Groweiss, A., Further Cembranoid Derivatives from the Red Sea Soft Corals Alcyonium flaccidum and Lobophytum crassum. J. Org. Chem. 1981, 46, 3592-3596.
28. Kobayashi, M.; Hirase, T., Marine Terpenes and Terpenoids. XI. Structures of New Dihydrofuranoocebranoids Isolated from a Sarcophyton sp. Soft Coral of Okinawa. Chem. Pharm. Bull. 1990, 38, 2442-2445.
29. Dong, H.; Gou, Y.-L.; Kini, R. M.; Xu, H.-X.; Chen, S.-X.; Teo, S. L. M.; But, P. P. H., A New Cytotoxic Polyhydroxysterol from soft coral sarcophyton trocheliophorum. Chem. Pharm. Bull. 2000, 48, 1087-1089.
30. Uchio, Y.; Nitta, M.; Nakayama, M.; Iwagawa, T.; Hase, T., Ketoemblide and Sarcophytolide, Two New Cembranolides with -Lactone Function from the Soft Coral Sarcophyta elegans. Chem. Lett. 1983, 613-616.
31. Zhang, C.; Li, J.; Su, J.; Liang, Y.; Yang, X.; Zheng, K.; Zeng, L., Cytotoxic Diterpenoids from the Soft Coral Sarcophyton crassocaule. J. Nat. Prod. 2006, 69, 1476-1480.
32. Gross, H.; Kehraus, S.; Nett, M.; König, G. M.; Beil, W.; Wright, A. D., New Cytotoxic Cembrane Based Diterpenes from the Soft Corals Sarcophyton cherbonnieri and Nephthea sp. Org. Biomol. Chem. 2003, 1, 944-949.
33. Nagashima, F.; Asakawa, Y., Sesqui- and Diterpenoids from Two Japanese and Three European Liverworts. Phytochemistry 2001, 56, 347-352.
34. Feller, M.; Rudi, A.; Berer, N.; Goldberg, I.; Stein, Z.; Benayahu, Y.; Schleyer, M.; Kashman, Y., Isoprenoids of the Soft Coral Sarcophyton glaucum: Nyalolide, a New Biscembranoid, and Other Terpenoids. J. Nat. Prod. 2004, 67, 1303-1308.
35. Kang, S. S.; Kim, J. S.; Son, K. H.; Kim, H. P.; Chang, H. W., Cyclooxygenase-2 Inhibitory Cerebrosides from Phytolaccae Radix. Chem. Pharm. Bull. 2001, 49, 321-323.
36. Wenzao J.; Kenneth L. R.; Elizabeth A. J., Ophidiacerebrosides: Cytotoxic Glycosphingolipids Containing a Novel Sphingosine from a Sea Star. J. Org. Chem. 1994, 59, 144–147.
37. Tan, J.-W.; Dong, Z.-J.; Liu, J.-K., New Cerebrosides from the Basidiomycete Cortinarius tenuipes. Lipids 2003, 38, 81-84.
38. Zhang, G. W.; Ma, X. Q.; Zhang, C. X.; Su, J.Y.; Ye, W. C.; Zhang, X. Q.; Yao, X. S.; Zeng, L. M., Two New Ceramides from the Marine Sponge Ircinia fasciculata. Helv. Chim. Acta 2005, 88, 885-890.
39. Johansen J. E.; Borch G.; Jensen S. L., Chirality of Peridinin and Dinoxanthin Phytochemistry, 1980, 19, 441–444.
40. Strain H. H.; Svec W. A.; Wegfahrt P.; Rapoport H.; Haxo F. T.; Norgard S.; Kjosen H.; Jensen S. L., Algal Carotenoids. XIV. Structural Studies on Peridinin. Part 1. Structure Elucidation Acta Chem. Scan. B 1976, 30, 109–120.
41. Krane, J.; Aakermann, T.; Liaaen-Jensen, S., Algal Carotenoids 47*- NMR Study of All-Trans-Peridinin, Including Complete 1H and 13C NMR Assignments. Magn. Reson. Chem. 1992, 30, 1169-1177.
42. Yamada, K.; Ryu, K.; Miyamoto, T.; Higuchi, R., Bioactive Terpenoids from Octocorallia. 4. Three New Cembrane-Type Diterpenoids from the Soft Coral
Lobophytum schoedei. J. Nat. Prod. 1997, 60, 798-801.
43. Tanaka, C. M. A.; Sarragiotto, M. H.; Zukerman-Schpector, J.; Marsaioli, A. J., A Cembrane from Echinodorus Grandiflorus. Phytochemistry 1997, 44, 1547-1549.
44. Duh, C.-Y.; Hou, R.-S., Cytotoxic Cembranoids from the Soft Corals Sinularia gibberosa and Sarcophyton trocheliophorum. J. Nat. Prod. 1996, 59, 595-598.
45. Coll, J. C.; Hawes, G. B.; Liyanage, N.; Oberhansli, W.; Wells, R. J., Studies of Australian Soft Corals. I* A New Cembrenoid Diterpene from a Sarcophyton Species. Aust. J. Chem. 1977, 30, 1305-1309.
46. Lin, S. T.; Wang, S. K.; Cheng, S. Y.; Duh, C. Y., Lobocrasol, a New Diterpenoid from the Soft Coral Lobophytum crassum. Org. Lett. 2009, 11, 3012-3014.
47. Lu, Y.; Lin, Y. C.; Wen, Z. H.; Su, J. H.; Sung, P. J.; Hsu, C. H.; Kuo, Y. H.; Chiang, M. Y.; Dai, C. F.; Sheu, J. H., Steroid and Cembranoids from the Dongsha Atoll Soft Coral Lobophytum sarcophytoides. Tetrahedron 2010, 66, 7129-7135.
48. Liu, Z.; Li, W. Z.; Peng, L.; Li, Y.; Li, Y., First Enantioselective Total Synthesis of (Natural) (+)-11,12-Epoxy 11,12-dihydrocembrene-C and (−)-7,8-epoxy-7,8-dihydrocembrene-C. J. Chem. Soc., Perkin Trans.1 2000, 4250-4257.
49. Geran, R. I.; Greenberg, N. H.; MacDonald, M. M.; Schumacher, A. M.; Abbott, B. J., Protocols for Screening Chemical Agents and Natural Products Against Animal Tumors and Other Biological Systems. Cancer Chemother Rep. Part 3 1972, 3, 1–91.
50. Stevens, M.; Balzarini, J.; Tabarrini, O.; Andrei, G.; Snoeck, R.; Cecchetti, V.; Fravolini, A.; De Clercq, E.; Pannecouque, C. “Cell-Dependent Interference of a Series of New 6-Aminoquinolone Derivatives With Viral (HIV/CMV) transactivation” J. Anal. Chem. 2005, 56, 847–855.
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