臺灣博碩士論文加值系統

β-carboline類化合物具有不錯的抗腫瘤和抗病毒的生物活性，所以引起我們對其衍生物之合成和藥理研究的興趣。本實驗應用簡單的Pictet-Spengler合成反應再以DDQ氧化得到一系列1-substitutedβ-carboline衍生物。化合物88-91是利用以tryptamine做起始物加入各種N-substituted-3-carbazole carboxaldehyde合成而得到的，然後將化合物88-91分別氧化成化合物92-95所有的化合物之結構是由各種光譜分析方法來確定的。而這一系列化合物已送往 國立中國醫藥研究所來進行細胞毒殺活性的測試，並藉此來研究化合物結構與生物活性的關係。測試結果顯示化合物88及93分別對肝癌（Hepa）及鼻咽癌（KB）細胞具有較佳的毒殺活性，其值分別為1.12 μg/ml及0.48 μg/ml。而第九位氮上的長鏈取代基越長活性則越弱，當碳數為16或20時，如化合物90、91、94及95，活性則完全消失。
另一方面，於蘭嶼取得的海綿Cacospongia sp.以甲醇/氯仿萃取後，其萃取物利用矽膠管柱分離，得到fasciculatin異構物 (97), 此化合物之結構利用了紫外線光譜、紅外線光譜、質譜、一維和二維的核磁共振譜來測定。

Previously, the naturalβ-carboline metabolites as potent antitumor and antival agents have spurred a great interest on the synthetic and pharmacological studies ofβ-carboline derivatives. Herein, a simple synthetic method by the application of Pictet-Spengler reaction and DDQ oxidation allowed the preparation of 1-substitutedβ-carboline derivatives. Compounds 88-91 were synthesized from tryptamine and N-substituted-3-carbazole carboxaldehyde via Pictet-Spengler cyclization. Then, oxidation of compounds 88-91 by DDQ provided compounds 92-95. Their structures were determined by spectroscopic methods. Biological screening revealed that compounds 88 and 93 possessed in vitro cytotoxicties against two tumor cell lines (KB, Hepa), respectively. The ED50 value of compound 88 showed cytotoxicities against Hepa (Human hepatoma) tumor cell lines were 1.12 μg/ml. The ED50 value of compound 93 showed cytotoxicities against KB (Human oral epidermoid carcinoma) tumor cell lines were 0.48 μg/ml.
On the other hand, the marine sponge Cacospongia sp. was collected along seashore area of Lan-Yu in Taiwan. Fractionation of the MeOH/CHCl3 extract by using silica gel column chromatography yielded a dauble bond isomer fasciculatin (97). The structure of 97 was identified by UV、IR、MS、1D and 2D NMR.

壹、生物活性1-Substituted-β-carboline衍生物的合成
一、緒論 1
二、研究動機 9
三、合成結果與結構鑑定 12
（一）合成結果 12
（二）結構鑑定 15
四、討論 30
五、實驗部份 33
（一）儀器 33
（二）試劑 33
（三）實驗方法和數據 34
貳、台灣產海綿Cacospongia sp.之成分研究
一、緒論 128
（一）前言 128
（二）Cacospongia sp.之成分介紹 129
（三）C-25 furanosesterterpens之文獻回顧 130
二、材料與方法 133
（一）材料 133
（二）分離方法簡述 133
三、結果與討論 135
（一）化合物97之分子結構鑑定 147
（二）衍生物118之分子結構鑑定 139
（三）衍生物119之分子結構鑑定 139
四、實驗部分 140
（一）儀器與材料 140
（二）成分之分離 141
（三）化合物97之分離純化 141
（四）衍生物118之製備 142
（五）衍生物119之製備 142
　參、參考文獻 154

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