PD 125375三環結構的合成研究 Synthetic Studies toward tricyclic ring of PD 125375

dc.contributor 簡敦誠 zh_TW
dc.contributor Chien, Tun-Cheng en_US
dc.contributor.author 蔣佳穎 zh_TW
dc.contributor.author Chiang, Chia-Yin en_US
dc.date.accessioned 2019-09-04T09:08:11Z
dc.date.available 不公開
dc.date.available 2019-09-04T09:08:11Z
dc.date.issued 2017
dc.description.abstract 1987年由C. Rithner團隊在Streptomyces achromogenes中所分離出三種化合物,兩種為具有pyrrolobenzodiazepine (PBD)結構的生物鹼,且具有抗菌活性的已知化合物Tomaymycin和Oxotomaymycin,第三種為本篇主要化合物PD 125375。PD 125375具有5-6-5三環結構且含有兩個連續的手性中心,在pyrrolidine上具有一個E form的3- ethylidine取代,而結構是與Tomaymycin類似,雖然PD 125375與Tomaymycin皆有3-ethylidinepyrrolidine的結構,但PD 125375的生物合成途徑及全合成是尚未被研究的,而我們則致力於利用化學合成途徑去合成出PD 125375,我們開發了一個使用簡單的方法,讓氮上具有保護的prolinal與N-Ts-pyrrole利用LDA的鹼性條件下進行反應,進而得到具有高立體選擇性的單一產物,經由一些官能基的轉換,再由分子內提供羰基和進行分子內合環反應而得到5-6-5三環結構之化合物。 zh_TW
dc.description.abstract PD 125375 and the well-known antibiotic Tomaymycin, a pyrrolobenzodiazepine (PBD) alkaloid, were isolated from the Streptomyces achromogenes and characterized by C. Rithner. It has a 5-6-5 tricyclic core with two contiguous chiral carbons, as well as the E form of 3-ethylidene on the pyrrolidine ring, which was structurally related to Tomaymycin. Although the novel structure of PD 125375 includes the 3-ethylidenepyrrolidine moiety also present in Tomaymycin, the biosynthetic pathway leading to PD 125375 is not developed. We were particularly interested in the synthesis of PD 125375. We have developed a simple method to synthesize the coupled product from N-protected prolinal and lithiated N-Ts-pyrrole by LDA with high stereoselectivity. After functional group manipulations, the removal of both N-protecting groups, and the introduction of the bridged carbonyl group between two nitrogens, the 5-6-5 tricyclic core could be obtained as a single stereoisomer in 11 synthetic steps. en_US
dc.description.sponsorship 化學系 zh_TW
dc.identifier G060342083S
dc.identifier.uri http://etds.lib.ntnu.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=id=%22G060342083S%22.&%22.id.&
dc.identifier.uri http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/100088
dc.language 中文
dc.subject 脯胺酸 zh_TW
dc.subject 吡咯 zh_TW
dc.subject 全合成 zh_TW
dc.subject proline en_US
dc.subject pyrrole en_US
dc.subject PD 125375 en_US
dc.title PD 125375三環結構的合成研究 zh_TW
dc.title Synthetic Studies toward tricyclic ring of PD 125375 en_US