(100.26.179.251) 您好!臺灣時間:2021/04/12 19:43
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:陳文娟]
研究生(外文):Chen, Wen chuan
論文名稱:I.Ceanothicacid之化學結構修飾及生物活性研究II.亞洲濱棗葉部之成分研究
論文名稱(外文):I. Preparation and Biological Effects of Ceanothic acid derivatives II. Chemical constituents from the leaves of Colubrina asiatica(L.) Brongn.
指導教授:李水盛
指導教授(外文):Lee Shoei-Sheng
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥學系
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
畢業學年度:85
語文別:中文
論文頁數:4
中文關鍵詞:亞洲濱棗生物活性
外文關鍵詞:Ceanothic acidColubrina asiatica
相關次數:
  • 被引用被引用:0
  • 點閱點閱:210
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
中文摘要
本論文包括二部分: 第一部分
:Ceanothic acid之化學結構修飾及生物活性研究 第二部分:亞洲濱棗
葉部之成分研究 第一部分:
Betulinic acid為lupane型之triterpene類化合物,廣泛分布於植物界,
據報導其有細胞毒性及抗人類免疫不全病毒 (HIV) 之活性。與其結構類
似之ceanothic acid富含於鼠李科植物馬甲子 (Paliurus ramosissimus)
中,其結構除A環之部分結構---五員環及C-1接有COOH與betulinic acid
有差異外,其餘結構均相同,為進一步探討betulinic acid衍生物之細胞
毒性及抗人類免疫不全病毒之作用,本論文第一部分主要針對ceanothic
acid結構中C-1及C-3取代基進行結構修飾,以評估此縮環betulinic acid
衍生物抗HIV反轉錄脢 (RT) 及癌細胞之活性。本研究將crude ceanothic
acid進行O-benzylation,得到ceanothic acid 2,28-dibenzyl ester為
起始物,以製備2-norceanothane及ceanothane衍生物,主要化學反應步
驟包括:PCC氧化3-OH為酮基;在LiI/γ-collidine加熱迴流下,進行去
芐基反應;LiALH4之還原反應,將酯基還為一級醇;脫水反應,而在C-1
與C-3間形成雙鍵。 初步生
物活性測試結果顯示這些化合物對HIV-RT沒有顯著抑制活性,但是
betulinic acid及屬於2-norceanothane衍生物之化合物5,6,10在10 mg/
ml對卵巢癌 (OV-3) 及子宮頸癌 (HeLa) 細胞有明顯的抑制活性。並由
IC50之betulinic acid之活性最強,在OV-3及HeLa細胞的IC50值分別
為0.88 mg/ml及0.81 mg/ml,所以A環仍以六員環最具細胞毒性。 第二
部分: 亞洲濱棗為
鼠李科植物,廣泛分布在熱帶及亞熱帶地區,據文獻報導其富含具安神作
用之dammarane類皂素 (jujubogenin glycoside)。本實驗室已從事具固
醇核之lanoster-ol類成分之微生物轉變研究,而dammarane型之
jujubogenin正屬於此類,因此本論文第二 部分是繼續研究本植物葉部之
jujubogenin glycoside成分,並研發製備真正非糖體juju- bogenin之方
法,以作為日後微生物轉變研究或製備具生物活性衍生物之用。 葉部
乙醇抽取物之氯仿可溶物用正己烷脫脂後,再以離心式分配層析儀、
Sephadex LH-20、成滴逆向層析法、低壓逆相管柱層析法及一般的吸附性
層析法,作進一步分離、 純化,共得到6個化合物,其中4個屬於
dammarane glycosides:colubrin (13), II-65-1(14), II-93-3 (15),
II-55-3 (16);2個屬於flavonol glycosides: rutin (17), ka-
empferol-3-O-rutinoside (18)。 另外,部分氯仿可溶物經Sephadex
LH-20劃分triterpene saponin及flavonol glyc-osides,saponin類再進
行酸水解及強鹼下氧化裂解反應,而分別得到ebelin lactone
(19) 及真正非糖體jujubogenin (20)。
這些化合物之結構係以包括二維核磁共振技術之光譜分析加以確認,其中
以化合物 14-16為首次分離之天然物。
I. Preparation and Biological Effects of Ceanothic acid
derivatives II. Chemical constituents from the leaves
of Colubrina asiatica (L.) Brongn.Part I
Betulinic acid, a lupane type triterpene widely distributed in
the plant kingdom, has been reported to possess cytotoxic and
anti-HIV activities. The structurally similar natural product
ceanothic acid, a abundant in rhamnaceousplant Paliurus
ramosissimus, possesses a carboxylic acid substitution at C-1
and a five-membered A ring instead of six-membered as in
betulinic acid. To further explore the anti-HIV activity and
cytotoxicity of betulinic acid derivatives, part I of this
thesis was aimed to prepare2-norceanothic acid analogues
from ceanothic acid, and assay their activities against human
immunodeficiency virus reverse transcriptase (HIV-RT) and cancer
cell lines. 2-Norceanothane and ceanothane derivatives were
prepared starting from ceanothic acid 2,28-dibenzyl ester,
obtained from o-benzylation. Major reaction steps included PCC
oxidation to give 3-oxo product, debenzylation with Lithium
iodide in γ-collidine under reflux, LiAlH4 reduction the ester
to give the primary alcohol, and dehydration to give double bond
between C-1 and C-3. The
biological tests demonstrated that these compounds had no
significant inhibition against HIV-RT, but betulinic acid and
2-norceanothane derivatives 5,6,10 (10 mg/ml) exhibited
significant inhibitory activity against OV-3 and HeLa cells.
From the IC50, betulinic acid is found to be the most potent
one, IC50 0.88 mg/ml and 0.81 mg/ml on OV-3 and HeLa cells,
respectively. Therefore , the six-membered A ring also played a
key role in cytotoxic activity. Part II
Colubrina asiatica (L.) Brongn., a rhamnaceous plant, is widely
distributed in tropical and subtropical areas. The dammarane
saponins (jujubogenin glycoside) possessing sedative effect was
reported to be rich in this plant. The microbial transformation
of lanosterol possessing steroid nucleus has beencarried out in
our laboratory, and the dammarane type jujubogenin isolated
from C. asiatica (L.) Brongn. also belong to this category.
Consequently, the second part of this thesis was aimed to
continue the study on the isolation of jujubogenin glycosides
from C. asiatica (L.) Brongn. and to develop method in
preparation of genuine aglycone jujubogenin from the glycosides,
for ng the further microbial transformation or for preparing the
derivatives as potential biologically active principles. The
chloroform soluble fraction of the EtOH extract of the leaves
was defatting by trituration with hexane. After that this
fraction was separated by combination of centrifugal partition
chromatography (C.P.C), Sephadex LH-20, lobar RP-18, droplet
counter current chromatography (D.C.C.C.) and the conventional
adsorption chromatography to give six compounds. Of these four
are dammarane glycosides, i.e. colubrin (13), II-65-1 (14),
II-93-3 (15), II- 55-3 (16); two are flavonoid glycosides, i.e.
rutin (17) and kaempferol-3-O- rutinoside (18). In addition,
part of chloroform soluble fraction was passed through a
Sephadex LH-20 column to remove flavonol glycosides. The
remaining saponin fraction was hydrolyzed under acid
conditions or oxidatively degraded under strong base conditions
to give ebelin lactone (19) and jujubogenin(20), respectively.
Structural elucidation of these comounds was based on elaborate
spectral analysis including 2D NMR techniques. Among these,
compounds 14-16 are novelnatural products.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔