Please use this identifier to cite or link to this item: http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/111114
Title: Yatein 和7-Deoxypodophyllotoxin 衍生物的合成研究
Synthetic Studies of Yatein and 7-Deoxypodophyllotoxin Derivatives
Authors: 簡敦誠
Chien, Tun-Cheng
杜岳樺
Tu, Yueh-Hua
Keywords: 7-脫氧鬼臼毒素
苯甲基碳陽離子
自由基
Yatein
7-deoxypodophyllotoxin
2-ODD
benzylic carbocation
radical
Issue Date: 2019
Abstract: 依托泊苷(Etoposide)是目前臨床使用的抗癌藥物,主要作用機制為抑制DNA拓樸異構酶II。雖然依托泊苷是世界衛生組織所列的基本藥物,但其製造需要從植物鬼臼中分離出(−)-鬼臼毒素((−)-podophyllotoxin),再利用人工合成得到。在2015年Sattely團隊研究顯示,此合成中的起始物(−)-鬼臼毒素,是以松柏醇經由多個酵素(DIR、PLR、SDH、 P450、OMT1及2-ODD)催化反應步驟得到。其中,我們有興趣的是Yatein在酵素2-ODD催化下,進行分子內合環反應,得到7-脫氧鬼臼毒素(7-deoxypodophyllotoxin)。為了探討酵素的反應機制,以β-piperonyl-γ-butyrolactone作為共同前驅物,合成酵素的受質Yatein和推測產物7-脫氧鬼臼毒素及其衍生物。我們的結果表明,最初提出的羥基化中間體不太可能參與該反應。相反,苯甲基自由基及碳陽離子中間體的形成可用於觸發碳–碳鍵形成以構建(-)-鬼臼毒素的碳環。
Etoposide is a clinically used anticancer drug. Its mechanism of action is inhibition of DNA topoisomerase II. Although etoposide is a basic drug listed by the World Health Organization, its manufacture requires the isolation of (−)-podophyllotoxin from plant scorpion as the precursor, followed by multi-step chemical synthesis. In 2015, Sattely’s team showed that the biosynthesis of (−)-podophyllotoxin was accomplished from coniferyl alcohol via multiple enzyme catalysis (DIR, PLR, SDH, P450, OMT1 and 2-ODD). In the biosynthetic pathway of (–)-podophyllotoxin, we have been interested to establish a reasonable reaction mechanism for 7-deoxypodophyllotoxin from yatein under 2-ODD-catalyzed oxidative cyclization. To study the 2-ODD catalyzed reaction, the synthesis of mechanistic probes, including yatein and deoxypodophyllotoxin analogs, started with β-piperonyl-γ- butyrolactone as a common precursorwas investigated.
URI: http://etds.lib.ntnu.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=id=%22G060642082S%22.&%22.id.&
http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/111114
Other Identifiers: G060642082S
Appears in Collections:學位論文

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