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研究生:黃景熙
研究生(外文):Jing-shi Huang
論文名稱:台灣產軟珊瑚Lemnalia flava、Efflatounaria tottoni和Klyxum simplex所含化學成分及其生物活性之研究
論文名稱(外文):Chemical Constituents and Biological Activity Studies of Formosan Soft Corals Lemnalia flava, Efflatounaria tottoni, and Klyxum simplex
指導教授:杜昌益杜昌益引用關係
指導教授(外文):Chang-Yih Duh
學位類別:碩士
校院名稱:國立中山大學
系所名稱:海洋生物科技暨資源學系研究所
學門:自然科學學門
學類:海洋科學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:166
中文關鍵詞:軟珊瑚
外文關鍵詞:Lemnalia flavaEfflatounaria tottoniKlyxum simplex
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在天然二次代謝物的研究中,本論文從台灣產穗花軟珊瑚Lemnalia flava中得到六個倍半萜類化合物,分別為GN76-9-1 (1)、GN76-10-3 (2)、GN76-12-6-10-1 (3)、GN76-25-1 (4)、GN76-25-5 (5)和GN76-30-5 (6)。其中GN76-9-1 (1)為一個具有ylangene骨架的新化合物。
此外,從台灣產花冠軟珊瑚Efflatounaria tottoni亦獲得一個alcyonolide骨架的雙萜類化合物GN79-11-3 (7)。
另外還有二個屬於germacrane骨架的已知倍半萜類化合物,則是從台灣產軟珊瑚Klyxum simplex中所分離得到,分別是GN82-11-4-2-15 (8)以及GN82-16-5-6-25 (9)。
以上化合物的結構皆是利用有機的光譜分析方法決定,並進行化合物的抗發炎活性試驗與神經細胞保護作用測試,發現化合物 2 對發炎性蛋白 iNOS (誘發型一氧化氮合成酶) 和 COX-2 (環氧酶-2) 有抗發炎活性以及化合物 8 對神經細胞 SH-SY5Y (人骨髓神經腫瘤細胞) 具有保護作用。
In our ongoing research for secondary metabolites from the Formosan soft corals, six sesquiterpenoids namely GN76-9-1 (1), GN76-10-3 (2), GN76-12-6-10-1 (3), GN76-25-1 (4), GN76-25-5 (5), and GN76-30-5 (6) were isolated from Lemnalia flava (GN76). Among these secondary metabolites, compound 1 possessing a ylangene-type skeleton is a new natural product.
Chromatographic separation of the extracts of the Formosan soft coral Efflatounaria tottoni yielded one known compound, GN79-11-3 (7), having an alcyonolide-type structure.
In addition, two known germacrane-type sesquiterpenoids, GN82-11-4-2-15 (8) and GN82-16-5-6-25 (9), were isolated from the extracts of the Formosan soft coral Klyxum simplex (GN82).
The structures of compounds 1 possessing a ylangene-type skeleton is a new natural product.
Chromatographic separation of the extracts of the Formosan soft coral Efflatounaria tottoni yielded one known compound, GN79-11-3 (7), having an alcyonolide-type structure.
In addition, two known germacrane-type sesquiterpenoids, GN82-11-4-2-15 (8) and GN82-16-5-6-25 (9), were isolated from the extracts of the Formosan soft coral Klyxum simplex (GN82).
The structures of compounds 1-9 were elucidated by extensive spectral analyses. The anti-inflammatory and neuro-protective activities of these compounds were measured in vitro. Compound 2 showed more specific inhibition against the increase of the pro-inflammatory iNOS and COX-2 proteins of LPS-stimulated RAW264.7 macrophage cells. Compound 8 also reveals more specific neuro protective activity to human neuroblastoma cells SH-SY5Y.
目錄
壹、緒論 1
一、前言 1
二、Lemnalia屬軟珊瑚之天然物化學研究回顧 4
三、Efflatounaria屬軟珊瑚之天然物化學研究回顧 14
四、Klyxum simplex軟珊瑚之天然物化學研究回顧 17
五、研究目的與動機 18
貳、GN76穗花軟珊瑚Lemnalia flava化學成分之研究 19
一、生物材料採集與鑑定 19
二、GN76穗花軟珊瑚Lemnalia flava之分類地位 19
三、GN76穗花軟珊瑚Lemnalia flava化學成分之萃取與分離流程 20
四、GN76穗花軟珊瑚Lemnalia flava化學成分之分離純化 22
1. GN76-9-1 (1) 之分離純化 22
2. GN76-9-1 (1) 之水解及(S)-MTPA ester 製備 25
3. GN76-9-1a (1a) 之(R)-MTPA ester 製備 27
4. GN76-10-3 (2)之分離純化 29
5. GN76-12-6-10-1 (3) 之分離純化 32
6. GN76-25-1 (4) 之分離純化 35
7. GN76-25-5 (5) 之分離純化 38
8. GN76-30-5 (6) 之分離純化 41
五、GN76穗花軟珊瑚Lemnalia flava化學成分之結構解析 44
1. GN76-9-1 (1) 之結構解析 44
2. GN76-10-3 (2) 之結構解析 59
3. GN76-12-6-10-1 (3) 之結構解析 64
4. GN76-25-1 (4) 之結構解析 68
5. GN76-25-5 (5) 之結構解析 73
6. GN76-30-5 (6) 之結構解析 78
叁、GN79花冠軟珊瑚Efflatounaria tottoni化學成分之研究 83
一、生物材料採集與鑑定 83
二、GN79花冠軟珊瑚Efflatounaria tottoni之分類地位 83
三、GN79花冠軟珊瑚Efflatounaria tottoni化學成分之萃取與分離流程 84
四、GN79花冠軟珊瑚Efflatounaria tottoni化學成分之分離純化 86
1. GN79-11-3 (7) 之分離純化 86
五、GN79花冠軟珊瑚Efflatounaria tottoni之結構解析 89
1. GN79-11-3 (7) 之結構解析 89
肆、GN82軟珊瑚Klyxum simplex化學成分之研究 100
一、生物材料採集與鑑定 100
二、GN82穗花軟珊瑚Klyxum simplex之分類地位 100
三、GN82軟珊瑚化學成分之萃取與分離流程 101
四、GN82軟珊瑚化學成分之分離純化 103
1. GN82-11-4-2-15 (8) 之分離純化 103
2. GN82-16-5-6-25 (9) 之分離純化 106
五、GN82軟珊瑚Klyxum simplex化學成分之結構解析 109
1. GN82-11-4-2-15 (8) 之結構解析 109
2. GN82-16-5-6-25 (9) 之結構解析 120
伍、生物活性之研究 130
一、抗發炎活性試驗之原理與方法 130
1. 抗發炎活性試驗原理 130
2. In vitro 抗發炎活性檢測方法 135
二、軟珊瑚化學成分抗發炎測試結果 137
三、神經細胞保護作用實驗之原理與方法 138
1. 神經細胞保護作用實驗之原理 138
2. 神經細胞保護作用實驗方法 139
四、軟珊瑚化學成分神經細胞保護作用試驗結果 140
陸、結論 142
柒、參考文獻 145
捌、附錄 152
一、儀器 152
二、材料 153
圖目錄
圖一、GN76穗花軟珊瑚Lemnalia flava化學成分之萃取與分離流程 21
圖二、GN76-9-1 (1) 之 碳譜 48
圖三、GN76-9-1 (1) 之 高解析ESI質譜 49
圖四、GN76-9-1 (1) 之 紅外光譜 50
圖五、GN76-9-1 (1) 之 氫譜 51
圖六、GN76-9-1 (1) 之 HSQC圖譜 52
圖七、GN76-9-1 (1) 之 HSQC局部放大圖譜 53
圖八、GN76-9-1 (1) 之 COSY圖譜 54
圖九、GN76-9-1 (1) 之 HMBC圖譜 55
圖十、GN76-9-1 (1) 之 NOESY圖譜 56
圖十一、GN76-9-1b (1b) 之 氫譜 57
圖十二、GN76-9-1c (1c) 之 氫譜 58
圖十三、化合物1a之Mosher酯化反應後氫值差 47
圖十四、GN76-10-3 (2) 之 碳譜 61
圖十五、GN76-10-3 (2) 之 氫譜 62
圖十六、GN76-10-3 (2) 之 紅外光譜 63
圖十七、GN76-12-6-10-1 (3) 之 碳譜 65
圖十八、GN76-12-6-10-1 (3) 之 氫譜 66
圖十九、GN76-12-6-10-1 (3) 之 紅外光譜 67
圖二十、GN76-25-1 (4) 之 碳譜 70
圖二十一、GN76-25-1 (4) 之 紅外光譜 71
圖二十二、GN76-25-1 (4) 之 氫譜 72
圖二十三、GN76-25-5 (5) 之 碳譜 75
圖二十四、GN76-25-5 (5) 之 紅外光譜 76
圖二十五、GN76-25-5 (5) 之 氫譜 77
圖二十六、GN76-30-5 (6) 之 碳譜 80
圖二十七、GN76-30-5 (6) 之 紅外光譜 81
圖二十八、GN76-30-5 (6) 之 氫譜 82
圖二十九、GN79花冠軟珊瑚Efflatounaria tottoni化學成分萃取與分離流程
85
圖三十、GN79-11-3 (7) 之 碳譜 94
圖三十一、GN79-11-3 (7) 之 HSQC圖譜 95
圖三十二、GN79-11-3 (7) 之 COSY圖譜 96
圖三十三、GN79-11-3 (7) 之 氫譜 97
圖三十四、GN79-11-3 (7) 之 HMBC圖譜 98
圖三十五、GN79-11-3 (7) 之 NOESY圖譜 99
圖三十六、GN82軟珊瑚Klyxum simplex化學成分萃取與分離流程 102
圖三十七、GN82-11-4-2-15 (8) 之 碳譜 112
圖三十八、GN82-11-4-2-15 (8) 之 紅外光譜 113
圖三十九、GN82-11-4-2-15 (8) 之 HSQC圖譜 114
圖四十、GN82-11-4-2-15 (8) 之 氫譜 115
圖四十一、GN82-11-4-2-15 (8) 之 COSY圖譜 116
圖四十二、GN82-11-4-2-15 (8) 之 HMBC圖譜 117
圖四十三、GN82-11-4-2-15 (8) 之 HMBC局部放大圖譜 118
圖四十四、GN82-11-4-2-15 (8) 之 NOESY圖譜 119
圖四十五、GN82-16-5-6-25 (9) 之 碳譜 123
圖四十六、GN82-16-5-6-25 (9) 之 HSQC圖譜 124
圖四十七、GN82-16-5-6-25 (9) 之 HSQC局部放大圖譜 125
圖四十八、GN82-16-5-6-25 (9) 之 COSY圖譜 126
圖四十九、GN82-16-5-6-25 (9) 之 氫譜 127
圖五十、GN82-16-5-6-25 (9) 之 HMBC圖譜 128
圖五十一、GN82-16-5-6-25 (9) 之 NOESY圖譜 129
表目錄
表一、化合物1−6、8−9 之抗發炎測試結果 137
表二、化合物3−6 和8 神經細胞保護實驗結果 140
表三、化合物8 和6 神經細胞保護實驗結果 141
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