海洋無脊椎動物至今已被發現不少具有生物活性的二次代謝產物。我們對兩種軟珊瑚Lobophytum crassum 和Dendronephthya griffini的化學成分研究中，一共分離純化出28個化合物。從軟珊瑚Lobophytum crassum中分離出14個化合物，包含7個新的cembranoid類化合物，crassumolides A–G (1–7)，和3個 glycolipid化合物，(2R)-1-hydroxy-3-hexadecyloxy-propyl-β-D-arabinopyranoside (8)、 (2R)-1-hydroxy-3-octadecyloxy-propyl-β-D-arabinopyranoside (9)、 以及 (2R)-1-acetoxy-3-hexadecyloxy-propyl-β-D-arabino-pyranoside (10)，以及4個已知化合物分別為lobohedleolide (11)、17-dimethylaminolobo- hedleolide (12)、 sinulariol A (13)、和denticulatolide (14)。從軟珊瑚Dendronephthya griffini純化出10個新的固醇類化合物griffinisterones A–J (15–24)，同時也得到1個已知化合物15-chlorogriffinsulfate (25)、3個新的直鏈多氯取代的化合物，包含 griffinsulfate (26)、15-chlorogriffinol (27)、與griffinol (28)。以上化合物的結構鑑定是經由各種光譜資料的分析。C-24位置的異構物(15和16)除了利用二維NMR圖譜的解析之外，也利用15的單晶繞射來加以鑑定。
我們將在軟珊瑚中大量的已知化合物lobohedleolide (11)拿來作化學結構修飾進而得到化合物29–34。將11以meta-chloro- peroxybenzoic acid (MCPBA)氧化得到29和30；以SeO2氧化可以得到31。化合物34為使用11與1-hydroxybenzotriazole (HOBt)偶合反應時所得到的產物。將11進行OH基導引的Henbest epoxidation 得到化合物32，其非鏡相立體選擇性(diastereoselectivity)可以高達99％以上。11利用EDC-coupling反應進行甲基酯化反應得到33，過程中添加DMAP的鹽酸鹽類可以大大地提高產率，而所得到的甲基酯化合物33也得以讓我們定出3的絕對立體組態。上述天然以及結構修飾過的化合物的細胞毒活性和抗發炎活性也將在此論文中討論。

Marine invertebrate have been found to be a rich source of bioactive secondary metabolites. During the course of our investigation on the bioactive chemical constituents from marine invertebrates, twenty-eight metabolites have been isolated from two soft coral Lobophytum crassum and Dendronephthya griffini. Investigation on L. crassum has led to the isolation of fourteen compounds, including seven new cembranoids, crassumolides A–G (1–7), and three new glycolipids (2R)-1-hydroxy -3-hexadecyloxy-propyl-β-D-arabinopyranoside (8), (2R)-1-hydroxy-3- octadecyloxy-propyl-β-D-arabinopyranoside (9), and (2R)-1-acetoxy-3- hexadecyloxy-propyl-β-D-arabino-pyranoside (10), coupled with four known compounds, lobohedleolide (11), 17-dimethylaminolobohedleolide (12), sinulariol A (13), and denticulatolide (14). Ten new steroids, griffinisterones A–J (15–24), were isolated from the soft coral D. griffini, while a known, 15-chlorogriffinsulfate (25), and three new polychlorinated acyclic compounds，griffinsulfate (26), 15-chlorogriffinol (27), and griffinol (28), were also purified from the same organism. Structures of these metabolites were identified as new natural products by extensive spectroscopic methods. Except for the use of 2D NMR, the 24-epimers of 15 and 16 were identified by a single-crystal X-ray crystallography on 15.
Lobohedleolide (11), obtained in large quantity in L. crassum, has also been modified to 29–34 by chemical conversion. Oxidation with meta-chloro-peroxybenzoic acid (MCPBA) afforded compounds 29 and 30, and with selenium dioxide led to the formation of 31. Compound 34 is the product of O-coupling reaction of 11 with 1-hydroxybenzotriazole (HOBt). Over 99﹪diastereoselectivity was observed in the process of Henbest hydroxyl-directed epoxidation on 11 to yield 32. EDC-coupling with an aid of HCl salt of DMAP afforded methylester 33 in high yield, and proved the absolute stereochemistry of 3. The cytotoxicity and anti-inflammatory activities of the natural and modified compounds were also discussed herein.

目錄 I
圖目錄 IV
表目錄 XVII
中文摘要 XIX
英文摘要 XX
結構總圖及反應流程 XXII

第一章、緒論 1
第一節 研究背景與動機 1
第二節 物種形態與分類地位 6
第三節 相關文獻回顧 7

第二章、結果與討論
第一節 Lobophytum crassum的成分研究 23
(一) Crasslobonin A (1)之結構解析 23
(二) Crasslobonin B (2)之結構解析 32
(三) Crasslobonin C (3)之結構解析 39
(四) Crasslobonin D (4)之結構解析 46
(五) Crasslobonin E (5)之結構解析 53
(六) Crasslobonin F (6)之結構解析 61
(七) Crasslobonin G (7)之結構解析 68
(八) (2R)-1-Hydroxy-3-hexadecyloxy-propyl-β-D-
arabinopyranoside (8)之結構解析 75
(九) (2R)-1-Hydroxy-3-octadecyloxy-propyl-β-D-
arabinopyranoside (9)之結構解析 86
(十) (2R)-1-Acetoxy-3-hexadecyloxy-propyl-β-D-
arabinopyranoside (10)之結構解析 93
(十一) Lobohedleolide (11)之結構解析 101
(十二) 17-Dimethylaminolobohedleolide (12)之結構解析 104
(十三) Sinulariol A (13)之結構解析 107
(十四) Denticulatolide (14)之結構解析 110
第二節 Dendronephthya griffini的成分研究 113
(十五) Griffinisterone A (15)之結構解析 113
(十六) Griffinisterone B (16)之結構解析 121
(十七) Griffinisterone C (17)之結構解析 128
(十八) Griffinisterone D (18)之結構解析 135
(十九) Griffinisterone E (19)之結構解析 142
(二十) Griffinisterone F (20)之結構解析 151
(二十一) Griffinisterone G (21)之結構解析 159
(二十二) Griffinisterone H (22)之結構解析 166
(二十三) Griffinisterone I (23)之結構解析 173
(二十四) Griffinisterone J (24)之結構解析 181
(二十五) 15-Chlorogriffinsulfate (25) 189
(二十六 ) Griffinsulfate (26) 193
(二十七) 15-Chlorogriffinol (27) 199
(二十八) Griffinol (28) 206

第三節 Lobohedleolide之化學結構修飾
(二十九) 11R,12R-Epoxy-lobohedleolide (29)之結構解析 213
(三十) 11S,12S-Epoxy-lobohedleolide (30)之結構解析 220
(三十一) 13S-Hydroxy-lobohedleolide (31)之結構解析 228
(三十二) 11R,12R-Epoxy-13S-hydroxy-lobohedleolide (32)
之結構解析 235
(三十三) Lobohedleolide methyl ester (33)之結構解析 244
(三十四) O-Hydroxybenzotriazoyl-lobohedleolidate (34)之
結構解析 246

第四節 細胞毒殺以及抗發炎活性結果 252
2-4-1 細胞毒殺活性篩檢結果 252
2-4-2 抗發炎活性篩檢結果 253
第三章、結論 262

第四章、實驗方法以及設備 265
第一節 實驗器材及設備 265
第二節 樣品之採樣以及萃取分離 267
4-2-1 Lobophytum crassum 部分 267
4-2-2 Dendronephthya griffini 部分 269
第三節 化學反應步驟 270
4-3-1 製備化合物1的(S)-以及(R)-MTPA esters 270
4-3-2 酸性條件下水解化合物8 270
4-3-3 製備甘油醚8a的bis-(R)-MTPA ester (8b) 271
4-3-4 製備化合物8c與8d 272
4-3-5 製備化合物10的(S)-以及(R)-MTPA esters 273
4-3-6 將化合物10b轉換成8d 274
4-3-7 製備化合物19之(R)- 與(S)-PGME amides 274
4-3-8 酸性條件下水解化合物25與26 275
4-3-9 以MCPBA氧化化合物11 275
4-3-10 SeO2氧化化合物11 276
4-3-11 製備化合物32 277
4-3-12 製備化合物33 277
4-3-13 製備化合物34 278
第四節 生物活性篩檢實驗方法 279
4-4-1 細胞毒殺活性篩檢方法 279
4-4-2 抗發炎活性篩檢方法 281
第五章、參考文獻 283
附錄一、 X-ray data of compound 15 291
附錄一、 X-ray data of compound 30

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