中 文 摘 要

在墾丁南灣附近採集到Dysidea avara的海綿經由酒精浸泡後，利用管柱層析及高效液相層析儀加以分離純化，初步得到兩個化合物，這兩個化合物結構上的化學資料，經由核磁共振儀（300 MHz）、EIMS、FABMS、UV、IR、及旋光光度計的測試，並和文獻1比對，證實分別為avarol（1） 及avarone（2）。針對化合物1進行各種醯化反應，得到一系列的化合物14 ~ 20，此外並利用化合物methylhrdroxyquinone（21）來作半合成反應，得到化合物22 ~ 24。衍生物14~20及22~24之結構經核磁共振、質譜與各種光譜確認分別為2’,5’-O-dibenzoylavarol（14）、2’,5’-O-〔p-chlorobenzoyl〕avarol（15）、2’,5’-O-dicinnamoylavarol（16）、2’,5’-O-〔p-bromobenzoyl〕avarol（17）、2’,5’-O-dioctanoylavarol（18）、2’,5’-O-〔p-florobenzoyl〕avarol（19）、Diacetylavarol（20）、2’,5’-O-dibenzoyl methylhydroxyquinone（22）、2’,5’-O-〔p-chlorobenzoyl〕methylhydroxyquinone（23）、diacetylmethylhydroxyquinone（24）。利用這一系列的化合物分別送往中國醫藥研究所及國家衛生研究院來進行細胞毒殺活性及抗病毒活性實驗，並探討化合物結構與生物活性間的關係。

英文摘要

The marine sponge Dysidea avara was collected along south seashore area of Kenting. Fractionation of the EtOH extract by using silica gel column chromatografphy and HPLC yielded avarol（1） and avarone（2）. The structure elucidation of 1 and 2 was achieved by NMR（300 MHz）, EIMS, FABMS, UV, IR and specific rotation. In order to study the structure and activity relationship, compound 1 was acylated to yield a series of avarol derivaties（14 ~ 20）. In addition, three compounds（22 ~ 24） were prepared from methylhydroxyquinone via acylation. Derivatives 14 ~ 20 and 22 ~ 24 were confirmed by spectral methods including NMR, MS, UV and IR as 2’,5’-O -dibenzoylavarol（14）、2’,5’-O-〔p-chlorobenzoyl〕avarol（15）、2’,5’-O-dicinnamoyl -avarol（16）、2’,5’-O-〔p-bromobenzoyl〕avarol（17）、2’,5’-O -dioctanoylavarol（18）、2’,5’-O-〔p-florobenzoyl〕avarol（19）、Diacetylavarol（20）、methylhydroxyquinone（22）、2’,5’-O-〔p-chlorobenzoyl〕methylhydroxyquinone（23）、diacetylmethylhydroxyquinone（24）. All of these compounds were send to National Health Research Institute and National Research Institute of Chinese Medicine for antitumor and antiviral tests in vitro. The investigation of their structure and activity relationship is now in progress.

目 錄

一、 緒論 頁次
(一)前言----------------------------------------------------1
(二)同屬海綿過去之文獻回顧----------------------------------2
(三)研究目的------------------------------------------------6
二、 材料與方法
(一)材料----------------------------------------------------8
(二)分離方法簡述--------------------------------------------8
三、 結果與討論
(一) 化合物SP-ST17-C（1）分子結構之鑑定--------------------11
(二) 化合物SP-ST17-B-A（2）分子結構之鑑定------------------13
四、 衍生物的製備
（一）衍生物14 ~ 20 的製備---------------------------------------18
（1）2’,5’-O-dibenzoylavarol（14）之結構解析--------------------19
（2）2’,5’-O-〔p-chlorobenzoyl〕avarol（15）之結構解析----------22
（3）2’,5’-O-dicinnamoylavarol（16）之結構解析-------------------24
（4）2’,5’-O-〔p-bromobenzoyl〕avarol（17）之結構解析-----------26
（5）2’,5’-O -dioctanoylavarol（18）之結構解析-------------------28
（6）2’,5’-O-〔p-florobenzoyl〕avarol（19）之結構解析------------30
（7）Diacetylavarol（20）之結構解析-----------------------------34
（二）衍生物22 ~ 24 的製備---------------------------------------36
（1） 2’,5’-O-dibenzoylmethylhydroxyquinone（22）之結構解--------37
（2） 2’,5’-O -〔p-chlorobenzoyl〕methylhydroxyquinone（23）結構解析
----------------------------------------------------------39
（3）diacetylmethylhydroxyquinone（24）之結構解析---------------41
五、 實驗部分
(一) 儀器與材料-----------------------------------------------50
(二) Dysidea avara成分之分離方法-----------------------------51
(三) 化合物1之分離純化---------------------------------------52
(四) 化合物2之分離純化---------------------------------------53
(五) 2’,5’-O-dibenzoylavarol（14）之結構解析---------------------54
(六) 2’,5’-O-〔p-chlorobenzoyl〕avarol（15） 之結構解析---------55
(七) 2’,5’-O-dicinnamoylavarol（16）之結構鑑定-----------------56
(八) 2’,5’-O-〔p-bromobenzoyl〕avarol（17）---------------------57
(九) 2’,5’-O -dioctanoylavarol（18）----------------------------58
(十) 2’,5’-O-〔p-florobenzoyl〕avarol（19）---------------------59
(十一) Diacetylavarol（20）結構解析----------------------------60
(十二) 2’,5’-O-dibenzoylmethylhydroxyquinone（22）結構解析-------------------------------------------------------61
(十三) 2’,5’-O -〔p-chlorobenzoyl〕methylhydroxyquinone（23）結構解析-------------------------------------------------62
(十四) diacetylmethylhydroxyquinone（24）結構解析------------63
六、附錄
（一）人類鼻咽癌細胞及肝癌細胞毒殺活性測試---------------------64
（二）人類胃癌細胞活性測試-------------------------------------65
七、參考文獻-------------------------------------------------------66

七、參考文獻

1. L. Minale, R. Riccio and G. Sodano,“ Avarol, a novel sesquiterpenoid hydroquinone with a rearranged drimane skeleton from the sponge Dysidea avara ”, Tetrahedron letter, 1974, 38, pp 3401-3404.
2. G. Cimino, L. Cariello, S. Derosa, S. Destefano, L. Zanetti, “ Structure of 2 biologically-active sesquiterpenoid amino-quinones from the marine sponge Dysidea avara ”, Experientia ,1982, 38, pp 896-896.
3. A. Crispino, A. DE Giulio, S. Deb Rosa and G. Strazzullo,“ A new bioactive derivative of avarol from Dysidea avara ”, J. Nat. Prod., 1989, 52, PP. 646-648.
4. A. De Giulio, S. De Rosa, G. Di Vincenzo and G. Strazzullo,“ Further bioactive derivative of avarol from Dysidea avara ”, Tetrahedron, 1990 , 46 , pp. 7971-7976.
5. S. Hirsch, A. Rudi, “ New avarone and avarol derivatives from the marine sponge Dysidea cinerea ”, J. Nat. Prod., 1991, 54, PP. 92-97.
6. Y. C. Shen and P. W. Hsieh, “ New sesquiterpene hydroquinones from a taiwanese marine sponge Polyfibrospongia australis ”, J. Nat. Prod., 1997, 60, PP. 93-97.
7. R. Talpir, A. Rudi and Y. Kashman, “ Three new sesquiterpene hydroquinones form marine origin ”, Tetrahedron, 1994, 50, pp. 4179-4184.
8. Pretsch, Clerc, Seibl, and Simon, “ Table of spectral data for structure determination of organic compounds ”.
9. Silverstein, Bassler, and Morrill, “ Spectrometric identification of organic compounds”.
10. KA. Alvi, P. Crews, “ Sesquiterpenoid Quinones from the Sponge, Dysidea-Avara as Tyrosine Kinase Inhibitors ”, Abstracts of Papers of the American Chemical Society 1992, 204, pp 161.
11. A. Degiulio, S. Derosa, G. Divincenzo, G. Strazzullo,“ Further Bioactive Derivative of Avarol from Dysidea-Avara ”,Tetrahedron 1990, 46, pp 7971-7976.
12. F. Giordan, R. Puliti,“ Structure of the 2,5-Dimethyl Ether of Avarol, a Sesquiterpenoid Hydroquinone from the Marine Sponge Dysidea-Avara ”, Acta Crystallographica Section C-crystal Structure Communications 1987, 43, pp 985-988.
13. W. Muller, A. Maidhof, W. Sachsse, RK. Zahn, HC. Schroder, B. Diehlseifert, N. Dogovic, C. Becker, MJ. Gasic, “ Inhibition of Mitosis by Avarol, a Natural Product Isolated from the Sponge Dysidea Avara ”, Basic and Applied Histochemistry 1985, 29, pp 321-330.
14. R. Puliti, S. Derosa, CA. Mattia, “ 4'-Methylaminoavarone from Dysidea-Avara ”, Acta Crystallographica Section C-crystal Structure Communications 1998, 54, pp 1954-1957.
15. R. Puliti, S. Derosa, CA. Mattia,“ Studies on Avarol Derivatives - 2',5'-Diacetylavarol from Dysidea-Avara ”,
Acta Crystallographica Section C-crystal Structure Communications 1995, 51, pp 2163-2166.
16. R. Puliti, S. Derosa, CA. Mattia,“ Crystal Studies of Avarol Derivatives - 5'-Acetylavarol from Dysidea-Avara ”, Acta Crystallographica Section C-crystal Structure Communications 1995, 51, pp 1195-1198.