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研究生:尉世昌
研究生(外文):Shyh-Chang Yu
論文名稱:I、劍葉木姜子根部化學成分之研究II、Lycorine化學結構修飾之研究
論文名稱(外文):I、Studies on the Chemical Constituents from Roots of Litsea lancifolia II、Studies on the Chemical Structural Modification of Lycorine
指導教授:李水盛
指導教授(外文):Shoei-Sheng Lee
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:170
中文關鍵詞:離心式分配層析法
外文關鍵詞:CPC (Centrifugal Partition Chromatography)
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摘要
一、 劍葉木姜子根部化學成分之研究
二、 Lycorine化學結構修飾之研究
第一部份:
  樟科Litsea屬植物,以富含isoquinoline類成分著稱。為了建立樟科植物化學分類法及充實天然物化學資料庫,本論文乃繼續研究劍葉木姜子之化學成分。
  莖部已被本實驗室研究過,而僅發現其含有少量之生物鹼,本研究為根部,在一般酸鹼處理和有機溶劑分配抽取總生物鹼後,以離心式分配層析、快速管柱層析被分離得到五個 aporphine類生物鹼。它們是 laurolitsine (1), boldine (2), isoboldine (3),laurotetanine (4),和 norisoboldine (5)。 其中以 boldine (2) 為最主要成分 (0.02%,w/w)。水可溶部份由 Amberlite XAD-II、Sephadex LH-20、離心式分配層析及快速管柱層析的組合層析後,分離出 (-)-magnocurarine (6), norcorytuberine (9),及二個恩菎化合物。這些化合物的結構鑑定由光譜解析。
第二部份:
  Lycorine (10),是一個在石蒜科植物中含有之主要生物鹼,已被證實對 DNA 及 RNA 病毒有抑制活性。例如,它在 1μg/ml 的濃度下抑制流行性小兒麻痹症病毒。先前我們實驗室研究顯現這生物鹼富含於文珠蘭中。為探討結構和抗病毒活性之關係,在本論文的第二部份製備幾個 lycorine (10) 衍生物。
  Lycorine (10),起始物乃以一種簡易之分離方式由文珠蘭葉部獲得(產率1.36%)。其主要化學修飾包括氧化,和在弱酸及強酸條件下催化之氫化。而後者氫化反應在強酸環境下(H2,Pd-C,EtOAc/conc. H2SO4)產生七個產物(13-19)。其中有些是立體異構物,而它們之結構以 NOE、2D NMR,及CD 分析法鑑定。
  這些化學修飾產物(12-24)將被進行抗病毒及細胞毒性生物測試,其結果將可供作對抗病毒劑之基礎。

Abstract
I、 Studies on the Chemical Constituents from Roots of Litsea lancifolia
II、 Studies on the Chemical Structural Modification of Lycorine
Part I、
Lauraceaous plants of Litsea genus are noted for the existence of various isoquino-lines. In order to establish the chemotaxonomy of the Lauraceae and enrich the natural products chemical bank, this thesis was aimed to study continuously on the chemical constituents of L. lancifolia.
The stem portion had been studied in this laboratory and found that it contained little amount of alkaloids. After general acid-base treatment and organic solvent partition for extracting alkaloids, the free bases obtained were separated by centrifugal partition chromatography (CPC), and flash column to give five aporphine type alkaloids. They are laurolitsine (1), boldine (2), isoboldine (3), laurotetanine (4), and norisoboldine (5). Among these, boldine (2) is a major one (0.02% , w/w). The water soluble fraction after separation via the combination of chromatography on Amberlite XAD-II, Sephadex LH-20, CPC and flash column yielded (-)-magnocurarine (6), norcorytuberine (9), and two anthraquinones. The structural elucidation of these compounds was based on spectral analysis.
Part II、
Lycorine (10), a major alkaloid present in the Amaryllidaceae, has been demonstrated to possess inhibitory activity against DNA and RNA viruses. For example, it inhibited Poliomyelitis virus at a concentration of 1μg/ml. Previous studies in our laboratory revealed that this alkaloid was rich in Crinum asiaticum. To investigate the structure and anti-viral activity relationship, several lycorine (10) analogues were prepared in the second part of this thesis.
Lycorine (10), the starting material was obtained from the leaves of C. asiaticum
by a facile separation method (yield 1.36%). Major chemical modifications included oxidation and catalytical hydrogenation under weak and strong acidic conditions. The latter reaction under strong acid environment (H2, Pd-C, EtOAc / conc. H2SO4) yielded seven products (13-19). Some of these were stereoisomers and their structures were elucidated by NOE, 2D NMR and CD analysis.
Antiviral and cytotoxic bioassay on these chemically modified products (12-24) will be undertaken and the results will serve as a basis for further exploration of anti-viral agents.

總目錄
誌謝***************************************************I
摘要***************************************************II
Abstract***********************************************III
總目錄*************************************************IV
表目錄 ( List of Tables )******************************VI
圖目錄 ( List of Figures )***************************** VII
流程圖目錄 ( List of Schemes)************************** XI
Glossary*********************************************** XI
第一部份:劍葉木姜子根部化學成分之研究
壹、 諸論與研究目的************************************1
1.1 植物簡介*****************************************1
1.2 木姜子屬植物化學成分之相關研究*******************1
1.3 研究目的***************..************************14
貳、 實驗結果與討論************************************14
2.1 Aporphine 類生物鹼化合物*************************16
2.1.1 Laurolitsine (1)******************************16
2.1.2 Boldine (2)***********************************16
2.1.3 Isoboldine (3)********************************17
2.1.4 Laurotetanine (4)*****************************17
2.1.5 Norisoboldine (5)*****************************18
2.1.6 Norcorytuberine (9)***************************18
2.2 四級生物鹼***************************************20
2.2.1 (-)-Magnocurarine (6)*************************20
2.3 Anthraquinone 類化合物***************************20
2.3.1 1-O-β-D-Glucopyranosyl-emodin (7)************20
2.3.2 Compound (8)**********************************22
2.4 結論*********************************************22
參、實驗部份*******************************************23
3.1 儀器與器材***************************************23
3.1.1 理化性質測定儀器******************************23
3.1.2 成分分離之儀器與材料**************************23
3.1.3 試劑(材料)及溶劑****************************23
3.1.4 薄層層析展開溶媒系統**************************24
3.2 抽取與分離***************************************24
3.2.1 氯仿可溶部份之成分分離************************24
3.2.2 水層可溶部份之成分化合物 (6) - (9) 之分離*****29
第二部份:Lycorine 結構化學修飾之研究******************32
壹、 諸論與研究目的************************************32
貳、 實驗結果與討論************************************32
2.1 Lycorine (10)之萃取與分離************************39
2.2 Diacetyllycorine (11)之製備**********************39
2.3 Dihydrolycorine (12)之製備***********************40
2.4 化合物 (13)-(19)之製備與結構解析*****************40
2.5 Dihydrodiacetyllycorine (20)之製備***************47
2.6 化合物 (21)之製備********************************48
2.7 化合物 (22)之製備********************************48
2.8 化合物 (23)之製備********************************48
2.9 化合物 (24)之製備與分離**************************49
參、實驗部份*******************************************50
3.1 儀器與器材***************************************50
3.1.1 理化性質測定儀器******************************50
3.1.2 成分分離之儀器與材料**************************50
3.1.3 試劑(材料)及溶劑****************************50
3.1.4 薄層層析展開溶媒系統**************************51
3.2 Lycorine (10)之萃取與分離************************51
3.3 Diacetyllycorine (11)之製備**********************52
3.4 Dihydrolycorine (12)之製備***********************52
3.5 化合物 (13)-(19)之製備與分離*********************53
3.6 Dihydrodiacetyllycorine (20)之製備***************58
3.7 化合物 (21)之製備********************************59
3.8 化合物 (22)之製備********************************60
3.9 化合物 (23)之製備********************************60
3.10 化合物 (24)之製備與分離*************************61
肆、參考文獻*******************************************63
伍、附圖 (Spectra Appendices)**************************67

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