- 學位論文
Stereocontrolled Synthesis of Prostaglandin via Multicomponent Anion-Relay Strategy
Stereocontrolled Synthesis of Prostaglandin via Multicomponent Anion-Relay Strategy
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摘要
本研究主題為合成 (±)-15-deoxy-Prostaglandin E2 以及 (-)-Prostaglandin E2 methyl ester。 此合成之主要策略為: (i) 利用雷福馬斯基之不對稱醛醇反應建立C11之立體中心; (ii) 利用異原子誘導共軛加成(HADCA)反應建立高立體選擇性之產物; iii) Brook重排反應; (iv) 分子內環化反應。其中(ii)-(iv) 可藉由一鍋化反應而得到具多官能基之五圓環產物。此五圓環產物可再與前列腺素的支鏈進行烷基化反應，之後再藉由去磺酸酯化反應以及去矽烷基反應可合成天然物(±)-15-deoxy-Prostaglandin E2以及 (-)-Prostaglandin E2 methyl ester。此反應總產率分別為34%和24%。本研究同時也探討利用苯硫基作為在不對稱炔類之引導官能基用於進行高位向選擇性的矽氫化反應。
並列摘要
Two total syntheses of (±)-15-deoxy-Prostaglandin E2 and (-)-Prostaglandin E2 methyl ester are completed through heteroatom-directed conjugate addition (HADCA). The key steps in this strategy are (i) Samarium-Reformatsky asymmetric aldol reaction; (ii) substrate control HADCA reaction in highly stereoselective manner; (iii) 1,4-Brook rearrangement; (iv) intramolecular cyclization to produce cyclopentanone, especially, (ii)-(iv) were achieved in one-pot reaction. Alkylation of the α-side chain with ketosulfone then followed by desulfonylation and desilylation afforded the (±)-15-deoxy-PGE2 and (-)-PGE2 methyl ester in 34% and 24% yield respectively. Highly regioselective hydrosilylation of unsymmetric alkynes using phenylthio moiety as directing group and also discussed in this dissertation.
參考文獻
References and Notes
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