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博碩士論文 etd-0724116-095035 詳細資訊
Title page for etd-0724116-095035
論文名稱
Title
海洋真菌 Fusarium solani 之化學成分及其活性研究; Vitroprocines和其衍生物之合成研究
Study on the Chemical Constituents of Marine-Derived Fungus, Fusarium solani and Their Biological Activities.; Study on the Synthesis of Vitroprocines and Its Derivatives.
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
183
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
2016-06-15
繳交日期
Date of Submission
2016-10-17
關鍵字
Keywords
天然化合物、抗生素、胺基酸-聚酮衍生物、海洋弧菌、口腔癌、細胞毒殺、仙人掌桿菌、茄型鐮胞菌、海洋真菌
marine fungus, Fusarium solani, Bacillus cereus, cytotoxicity, oral cancer, natural product, amino-polyketide derivatives, antibiotics, marine Vibrio sp.
統計
Statistics
本論文已被瀏覽 5647 次,被下載 34
The thesis/dissertation has been browsed 5647 times, has been downloaded 34 times.
中文摘要
第一部分

為了搜尋新穎的海洋真菌之抗微生物二次代謝物,我們找到一隻菟葵共生真
菌,茄型鎌胞菌 (Fusarium solani)。此真菌是在台灣屏東縣的萬里桐採集。從茄
型 鐮 胞 菌 的 乙 酸 乙 酯 (ethyl acetate) 萃 取 物 都 具 有 對 抗 鮑 氏 不 動 桿 菌
(Acinetobacter baumannii)和仙人掌桿菌(Bacillus cereus)的活性。

利用抗微生物活性導引分離法和高效能液相層析儀(HPLC)純化,我們從茄
型鐮胞菌(F. solani)的乙酸乙酯萃取物中得到十個 1, 4-萘醌衍生物(110)。上述化
合物的結構解析都是藉由 1D 和 2D NMR 光譜以及質譜,並且比對文獻得到的。
其中,化合物 1 和 2 在資料庫中並沒有找到相同的化合物,可能是新化合物。在
初步的抗菌活性試驗之中,發現化合物 1 對仙人掌桿菌(B. cereus)有抑制活性。
此外,化合物 1 和 2 對癌細胞株 HSC-3 和 Ca9-22 具有細胞毒殺活性。


第二部分

Vitroprocines 是一系列胺基酸-聚酮衍生物,此類化合物是由海洋弧菌 Vibrio
sp. QWI-06 中所分離出來的。在研究中發現,vitroprocines 這類化合物具有抑制
鮑氏不動桿菌(Acinetobacter baumannii)的抗菌活性,此菌為一種伺機性致病菌,
會影響免疫力低下的人。某些突變形的鮑氏不動桿菌具有多重抗藥性,醫院內感
染會導致死亡率增加。因此,尋找能抑制鮑氏不動桿菌的抗生素是非常急切的。

基於 vitroprocines 這類化合物具有抗菌活性,我們嘗試進行 vitroprocine A 與
其類似的合成。利用逆合成分析以及參考文獻,我們設計出一個從 L-酪胺酸做為
起始物合成 vitroprocine A。在此論文將介紹我們所做的合成工作。
Abstract
Part 1

When searching the novel anti-microbial secondary metabolites from
marine-derived fungus. We found a symbiotic fungus, Fusarium solani (FS-01),
isolated from a Palythoa sp., collected from Wanlitong, Pingtung County, Taiwan.
The ethyl acetate (EA) extract of these two fungus showed inhibitory effects against
Acinetobacter baumannii and Bacillus cereus.

Based on the anti-microbial activity-directed fractionation and HPLC isolation,
we isolated ten 1, 4-naphthoquinone derivatives (110) from the EA extract of F.
solani. The structures of these isolates were elucidated by 1D and 2D NMR and MS
data and comparison with the literature data. In these compounds, compound 9 and 10
did not found the identical compounds in the database. Maybe these two compounds
were novel compounds. Furthermore, the anti-microbial activites of these isolates
showed compound 1 exhibited antibacterial activity against B. cereus. Moreover,
compound 1 exhibited cytotoxicity activity against HSC-3 and Ca9-22 cancer cell
line.


Part 2

Vitroprocines, a series of amino-polyketide derivatives, were isolated from the
marine bacterium, Vibrio sp. QWI-06. In our research, vitroprocines exhibited
significant antibacterial activity against Acinetobacter baumannii. A. baumannii is an
opportunistic pathogen and affects people with compromised immune systems. Some
mutant stains of A. baumannii showed multiple-drug resistance to increase the in-
hospital mortality. Therefore, it is urgent to search new antibiotic against A. baumannii.
Because of the interest in antibiotic properties of vitroprocines, we are trying to
synthesize vitroprocine A and its structural analogs. Based on the retrosynthesis
analysis and literatural survey, we designed a synthetic pathway from L-tyrosine.
Herein, we will describe our works on the synthesis vitroprocine A.
目次 Table of Contents
第一部分

論文審定書 i
公開授權書 ii
謝誌 iii
中文摘要 v
Abstract vi
目錄 vii
圖目錄 ix
表目錄 xii
Fusarium solani所分離到之化合物 xiv
第一章 緒論 1
第一節 前言 1
第二節 茄型鐮胞菌(Fusarium solani)的研究背景 3
第三節 茄型鐮胞菌(Fusarium solani)之文獻回顧 5
第二章 材料方法與分離流程 16
第一節 茄型鐮胞菌之樣品採集與鑑定 16
第三節 茄型鐮胞菌的萃取與分離流程 22
第三章 結構解析 31
第一節 Javanicin (1)之結構證明 31
第二節 Solaniol (2)之結構證明 37
第三節Anhydrojavanicin (3)之結構證明 43
第四節 5-hydroxy-8-methoxy-2,4-dimethylnaphtho[1,2-b]furan-6,9-dione (4)之結構證明 50
第五節 Fusarubin methyl ether (5)之結構證明 56
第六節 Anhydrofusurabin (6)之結構證明 63
第七節 2-acetonyl-5-hydroxy-7-methoxy-3-methyl-1,4-naphthoquinone (7)之結構證明 68
第八節 Bostrycoidin (8)之結構證明 76
第九節 5-hydroxy-8-methoxy-2,4-dimethyl-1H-benzo[g]indole-6,9-dione (9)之結構證明 81
第十節 2-acetonyl-8-amino-5-hydroxy-7-methoxy-3-methyl-1,4-naphthoquinone (10)之結構證明 88
第四章 生物活性測試 94
第一節 抗菌活性測試 94
第二節 細胞毒殺活性測試 95
第五章 結論 100
第六章 實驗相關部分 101
第一節 海洋微生物培養基 101
第二節 儀器設備與試藥 104
第三節 各化合物物理性質與光譜資料 106
第七章 參考文獻 112


第二部分


中文摘要 i
Abstract ii
目錄 iii
圖目錄 v
表目錄 vi
合成化合物列表 vii
第一章 緒論 1
第一節 前言 1
第二節 Tyroscherin與其類似物之介紹與全合成分析 3
Tyroscherin之全合成途徑(一) 3
Tyroscherin之全合成途徑(二) 5
(2RS,8R,10R)-YM-193221之全合成途徑 7
第二章 實驗結果與討論 8
第一節 Vitroprocine A之逆合成分析 8
第二節 Vitroprocine A之全合成途徑(一) 10
Part 1-A 10
Part 1-B 12
第三節 Vitroprocine A之全合成途徑(二) 13
第三章 結論 15
第四章 實驗材料與方法 16
第一節 實驗方法 16
步驟一 16
步驟二 17
步驟二之二 18
方法A-步驟三 18
方法A-步驟四 19
方法A-步驟五 20
方法B-步驟三 21
方法B-步驟四 22
合成(3-Bromopropoxy)-tert-butyldimethylsilane 23
合成popargyl alcohol, tert-butyldimethyl-silyl ether 23
第二節 化合物資料 24
L-tyrsoine (起始物) 24
L-tyrosine methyl ester (T1) 25
(S)-N-(tert-butoxycarbonyl)-tyrosine methyl ester (T2) 27
(S)-N-tert-butoxycarbonyl-O-benzyl-tyrosine methyl ester (T3) 30
(S)-N-tert-butoxycarbonyl-O-benzyl-N-α-methoxyl-N-α-methyl-tyrosinamide (T4) 33
tert-butyl (S)-[5-(tert-butyldimethylsilyloxy)-1-[4-(benzyl)benzyl]-2-oxopentyl]-methylcarbamate (T5) 36
Compound T7 38
Compound T8 39
(3-Bromopropoxy)-tert-butyldimethylsilane 41
第五章 參考文獻 43
參考文獻 References
第一部分

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