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博碩士論文 etd-0726106-104051 詳細資訊
Title page for etd-0726106-104051
論文名稱
Title
台灣產叢羽軟珊瑚Cespitularia sp.雙萜類成分研究
Studies on the diterpenoids of Formosan soft coral Cespitularia sp.
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
78
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
2006-07-12
繳交日期
Date of Submission
2006-07-26
關鍵字
Keywords
軟珊瑚
Cespitularia
統計
Statistics
本論文已被瀏覽 5671 次,被下載 1527
The thesis/dissertation has been browsed 5671 times, has been downloaded 1527 times.
中文摘要
為了研究癌細胞抑制活性的雙萜類化合物,本次實驗材料採自台灣東岸產軟珊瑚Cespitularia sp.之甲醇/二氯甲烷萃取物,以矽膠管柱層析和高壓液態層析儀分離純化後,得到7個diterpenoid化合物,依骨架區分為三大類,即具有 verticillane骨架的GXX-7-
L3-1-2(1)、G8-5-L2-8-1(3)和G8-4-L3-9-1(4),屬cespitularane骨架的GXX-7-L3-4-1(2),而G8-4-L3-7-1(5)和G8-4-L3-8-1(6)、cespitularin E(7)為norverticillane骨架,其中1-6為新化合物。這些化合物主要構造是有一個環外雙鍵以及三組甲基訊號。化合物1於C-20位置有一組乙酯訊號,且於C-11、C-12、C-10間有一組α,β-unsaturated ketone,而C-6位置接一組hydroxyl group;化合物3與1相比差異在C-10、C-11、C-12與C-20間形成一個含氧五元環,其中C-11、C-12位置的α,β-unsaturated ketone氧化成epoxy ring,且C-10位置的Ketone還原成hydroxyl group,並與C-20形成氧橋。化合物4於C-20為methyl group,並缺少C-6的hydroxyl group,且C-7與C-8雙鍵氧化成epoxy ring。化合物2於C-9至C-12和C-20間形成一個五元環,並於C-6與C-20上各有一組乙醯基的結構的構造。化合物5在C-10、C-11、C-12含有α,β-unsaturated ketone,且C-6位置為一個ketone。化合物6與5的差異在於C-6為hydroxyl group且C-7與C-8間雙鍵氧化成epoxy ring;化合物7與5差異只在C-6的Ketone 還原為hydroxyl group。所有化合物的結構鑑定皆藉由一維及二維核磁共振圖譜、紅外線光譜及質譜來建立,化合物1也利用Mosher’s method來確定立體化學構造,證明C-6位置的hydroxyl group為β位向。並將以上的新化合物進行HeLa, KB, Daoy, WiDr等癌細胞毒殺測試發現其ED50值皆大於20 μg/ml。
Abstract
To investigate the bioactive constituents for evaluation of cytotoxicity, six new diterpenoids(1-6)and one known compound(7)were isolated from a sample of soft coral Cespitularia sp. collected in Taiwan.These diterpenoids were divided into three skeletons: GXX-7-L3-1-2(1), G8-5-L2-8-1(3)and G8-4-L3-9-1(4)are verticillane skeleton. GXX-7-L3-4-1(2)possesses a cespitularane skeleton. G8-4-L3-7-1(5), G8-4-L3-8-1(6)and cespitularin E (7) contain a norverticillane skeleton.Compound 1 contains an α,β-unsaturated ketone at C-11, C-12 and C-10, an ethyl ester group at C-20 position, and a hydroxyl group at C-6 position. There is a α-hydroxy-β,γ-epoxy-δ-hydroxy furan in compound 3. Compound 4 contains a methyl group at C-20 position, an epoxy ring at C-7 and C-8 position, and loses a hydroxyl group at C-6. Compound 2 has two acetoxyl groups at C-6 and C-20 position. Compound 5 contains an α,β-unsaturated ketone at C-11, C-12 and C-10, and olefinic double bond at C-7 and C-8 conjugated with ketone group at C-6 .The olefinic double bond at C-7 and C-8 is oxygenized to an epoxy ring and the ketone at C-6 is reduced to a hydroxyl group in compound 6.The ketone in compound 5 is reduced to a hydroxyl group in compound 7. All of these structures were elucidated on basis of extensive spectroscopic analysis and chemical derivatization.The configuration of hydroxyl group at C-6 in 1 was determined to be β orientation by using Mosher’s method. All of the isolated diterpenoids were tested against a panel of human tumor cell lines.
目次 Table of Contents
目錄
頁次
壹、緒論 1
一、前言.................................................1
二、Cespitularia屬之天然物化學成分研究文獻回顧...........3
三、研究動機及目的.......................................10
貳、軟珊瑚Cespitularia sp.之化學成分研究 11
一、材料採集.............................................11
二、軟珊瑚Cespitularia sp.之分類地位....................11
三、軟珊瑚Cespitularia sp.之萃取與分離流程..............12
四、軟珊瑚Cespitularia sp.之分離純化....................16
(1)GXX-7-L3-1-2(1)之分離純化......................16
(2)GXX-7-L3-4-1(2)之分離純化......................18
(3)G8-5-L2-8-1(3)之分離純化.......................20
(4)G8-4-L3-9-1(4)之分離純化.......................22
(5)G8-4-L3-7-1(5)之分離純化.......................24
(6)G8-4-L3-8-1(6)之分離純化.......................26
(7)G8-4-L3-7-2(7)之分離純化.......................28

五、軟珊瑚Cespitularia sp.成分之化學結構解析.............34
(1)Gxx-7-L3-1-2(1)之結構解析......................34
(2)Gxx-7-L3-4-1(2)之結構解析......................47
(3)G8-5-L2-8-1(3)之結構解析.......................57
(4)G8-4-L3-9-1(4)之結構解析.......................67
(5)G8-4-L3-7-1(5)之結構解析.......................76
(6)G8-4-L3-8-1(6)之結構解析.......................86
(7)G8-4-L3-7-2(7)之結構分析.......................96
參、結論 102
肆、參考文獻 104
伍、附錄 108
使用儀器與材料......................................108







圖附錄
圖一、軟珊瑚Cespitularia sp.之分離流程(一).............14
圖二、軟珊瑚Cespitularia sp.之分離流程(二).............15
圖三、化合物1之1H-NMR數據指定............................17
圖四、化合物1之13C-NMR數據指定...........................17
圖五、化合物2之1H-NMR數據指定............................19
圖六、化合物2之13C-NMR數據指定...........................19
圖七、化合物3之1H-NMR數據指定............................21
圖八、化合物3之13C-NMR數據指定...........................21
圖九、化合物4之1H-NMR數據指定............................23
圖十、化合物4之13C-NMR數據指定...........................23
圖十一、化合物5之1H-NMR數據指定..........................25
圖十二、化合物5之13C-NMR數據指定.........................25
圖十三、化合物6之1H-NMR數據指定..........................27
圖十四、化合物6之13C-NMR數據指定.........................27
圖十五、化合物7之1H-NMR數據指定..........................29
圖十六、化合物7之13C-NMR數據指定.........................29圖十七、化合物1之Mosher’s Method........................37
圖十八、化合物1之NOESY立體圖............................37
圖十九、化合物1之1H-NMR圖譜..............................38
圖二十、化合物1之13C-NMR圖譜.............................39
圖二十一、化合物1之COSY圖譜.............................40
圖二十二、化合物1之HMQC圖譜.............................41
圖二十三、化合物1之HMBC圖譜.............................42
圖二十四、化合物1之NOESY圖譜............................43
圖二十五、化合物1之HRMS圖譜.............................44
圖二十六、化合物1之S-MTPA圖.............................45
圖二十七、化合物1之R-MTPA圖.............................46
圖二十八、化合物2之NOESY立體圖...........................49
圖二十九、化合物2之1H-NMR圖譜............................50
圖三十、化合物2之13C-NMR圖譜.............................51
圖三十一、化合物2之COSY圖譜.............................52
圖三十二、化合物2之HMQC圖譜.............................53
圖三十三、化合物2之HMBC圖譜.............................54
圖三十四、化合物2之NOESY圖譜............................55
圖三十五、化合物2之HRMS圖譜.............................56
圖三十六、化合物3之NOESY立體圖...........................59
圖三十七、化合物3之1H-NMR圖譜............................60
圖三十八、化合物3之13C-NMR圖譜...........................61
圖三十九、化合物3之COSY圖譜.............................62
圖四十、化合物3之HMQC圖譜...............................63
圖四十一、化合物3之HMBC圖譜.............................64
圖四十二、化合物3之NOESY圖譜............................65
圖四十三、化合物3之HRMS圖譜.............................66
圖四十四、化合物4之NOESY立體圖...........................69
圖四十五、化合物4之1H-NMR圖譜............................70
圖四十六、化合物4之13C-NMR圖............................71
圖四十七、化合物4之COSY圖譜.............................72
圖四十八、化合物4之HMQC圖譜.............................73
圖四十九、化合物4之HMBC圖譜.............................74
圖五十、化合物4之HRMS圖譜...............................75
圖五十一、化合物5之NOESY立體圖..........................78
圖五十二、化合物5之1H-NMR圖譜............................79
圖五十三、化合物5之13C-NMR圖............................80
圖五十四、化合物5之COSY圖譜.............................81
圖五十五、化合物5之HMQC圖譜..............................82
圖五十六、化合物5之HMBC圖譜..............................83
圖五十七、化合物5之NOESY圖譜............................84
圖五十八、化合物5之HRMS圖譜.............................85
圖五十九、化合物6之NOESY立體圖..........................88
圖六十、化合物6之1H-NMR圖譜.............................89
圖六十一、化合物6之13C-NMR圖譜...........................90
圖六十二、化合物6之COSY圖譜.............................91
圖六十三、化合物6之HMQC圖譜.............................92
圖六十四、化合物6之HMBC圖譜.............................93
圖六十五、化合物6之NOESY圖譜............................94
圖六十六、化合物6之HRMS圖譜.............................95
圖六十七、化合物7之1H-NMR圖譜............................97
圖六十八、化合物7之13C-NMR圖............................98
圖六十九、化合物7之COSY圖譜.............................99
圖七十、化合物7之HMQC圖譜..............................100
圖七十一、化合物7之HMBC圖譜............................101
圖七十二、化合物1-7之可能生合成路徑(一)................104
圖七十三、化合物1-7之可能生合成路徑(二)................105



表附錄
表一、化合物1-4之1H-NMR數據..............................30
表二、化合物1-4之1H-NMR數據..............................31
表三、化合物5-7之1H-NMR數據..............................32
表四、化合物5-7之1H-NMR數據..............................33
參考文獻 References
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2. Braekman J. C., Daloze D., Stoller C. and Declercq J. P.“ The Configuration of Palustrol and Related Compound”Bull. Soc. Chim. Belg. 1989,98,869-876.
3. Braekman J. C., Daloze D., Ottinger R. and Tursch B. “Chemical Studies of Marine Invertebrates. XXVII. On the
Absolute Configuration of Aromadendrane Sesquiterpenes
from the Soft Coral Cespitularia aff. Subviridis” Experientia 1977,33,993.
4. Bowden B. F., Coll J. C., Mitchell S. J., Stokie G. J. and Blount J. F.“Studies of Australian soft coral. VIII A Chemical and Crystallographic Study of a Novel Bicyclic Diterpene Alcohol with a Rearranged Skeleton from
an Unknown Species of Soft Coral”Aust. J. Chem. 1978, 31,
2039-2046.
5. Bowden B. F., Braekman J. C., Coll J. C. and Mitchell S. J. “Studies of Australian Soft Corals. XX A New Sesquiterpene Furan from Soft Corals of the Family Xeniidae and an Examination of Clavularia inflate from North Queensland Waters” Aust J. Chem. 1980, 33, 927-932.
6. Burns K. P., Kazlauskas R., Murphy P. T., Wells R. J. and Schönholzer P.“Two Cembrances from Cespitularia Species (Soft Coral)”Aust. J. Chem.1982, 35, 85-94.
7. Bowden B. F., Coll J. C. and Tapiolas D. M.“Studies of Australian Soft Coral. XXX A Novel Trisnorsesquiterpene form a Cespitularia Species and the Isolation of Guaiazulene from a small Blue Alcyonium Species” Aust. J. Chem. 1983, 36, 211-214.
8. Askoka M., Kosaka T., Itahana H., Takei H. “Total Synthesis of Clavukerin A and Its Epimer”Chem. Lett.1991,1295-1298.
9. Bowden B. F., Coll J. C., Gulbis J. M., Mackay M. F. and Willis R. H.“Studies of Australian Soft Corals. XXXVIII Structure Determination of Several Diterpenes Derived from a Cespitularia Species (Coelenterata, Octocorallia, Xeniidae)”Aust. J. Chem. 1986, 39, 803-812.
10. König G. M. and Wright A. D.“A New Caryophyllene-Based Diterpene from the Soft Coral, Cespitularia sp.”J. Nat. Prod. 1993, 56, 2198-2200.
11. Coll J. C., Kearns P. S. and Rideout J. A. “Isolation of Novel Diterpene Triacetate from Two Soft Corals of the Order Alcyonacea”J. Nat. Prod. 1998, 61, 835-837.
12. Duh C.-Y., El-Gamal A. A. H., Wang S.-K. and Dai C.-F. “Novel Terpenoids from Formosan Soft Carol Cespitularia Hypotentaculata”J. Nat. Prod. 2002, 64, 1028-1031.
13. Shen Y.-C., Lin Y.-S., Kuo Y.-H. and Cheng Y.-B. “Cespitulactams A, B, and C, three new nitrogen
-containing diterpenes from Cespitularia taeniata May”
Tetrahedron Letters 2005, 46, 7893
14. Shen Y.-C., Ho C.-J., Kuo Y.-H.與Lin Y.-S.
“Cespitulactones A and B, new diterpenoids from Cespitularia
taeniata”Bioorg. Med. Chem. Let.2006,16, 2369-2372.
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“ High-Field FT NMR Application of Mosher’s Method.The Absolute Configurations of Marine Terpenoids.”J. Am. Chem. Soc. 1991,113, 4092-4096.
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