Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/16829
標題: 探索(+)-Fawcettimine的合成途徑
Synthetic Studies toward (+)-Fawcettimine
作者: 王科棟
Wang, Ko-Tung
關鍵字: fawcettimine
阿茲海默症
total synthesis
全合成
出版社: 化學系所
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摘要: (+)-Fawcettimine的四環骨架是藉由丙烯酸甲酯經由三個步驟製備出銅試劑與(R)-環己烯酮進行Michael加成反應形成具有兩個不對稱中心的酮酯類化合物,接著在鹼性環境下進行分子內Dieckmann縮合反應,建構出cis- hydrindanone環系統,並創造出第三個不對稱中心。再與烷基溴化合物,進行分子間的碳-烷基化反應,創造出第四個四級碳不對稱中心,之後選擇性進行單邊三氟甲磺醯化反應(triflation),得到enol triflate化合物。接著使用關鍵步驟進行分子內Heck環合反應,合成出含氮九圓環與副產物八圓環化合物,而九圓環化合物再進行選擇性氫化反應,即可得到Toste中間物,最後經由Toste教授所發表的三個步驟即可全合成(+)-fawcettimine。
(+)-Fawcettimine has a tetracyclic framework containing a single quaternary carbon center.Stereocontrolled coupling addition of methyl 3-iodopropanate-derived zinc reagent to (+)-5-methyl-2-cyclohexenone, Application of the base-promated intramolecular Dieckmann condensation and a regiocontolled C-alkylation of 1,3-diketone enolate with t-butyl N-allyl,N-(2-bromoethyl)carbamate,and then implementation of a regioselective installation of enol triflate and palladium-catalyzed intramolecular coupling between triflate with alkene moiety led efficient to a readily separable mixture of tricyclic dienic ketone and its regioisomer..Chemoselective hydrogenation of dienic ketone with H2/Pd/C in MeOH proceeded without complication to give the monounsaturated tricyclic keto carbamate,which serves as a pivotal precursor to (+)-Fawcettimine.
URI: http://hdl.handle.net/11455/16829
其他識別: U0005-2707201015130600
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