環狀α-胺基酸的脫羰基碳－碳鍵形成反應:合成2號位置取代哌啶與吡咯啶之生物鹼

Abstract

本論文主要探討的是氮上具有烷基取代環狀α-胺基酸的脫羰基碳－碳鍵形成反應，其關鍵步驟為利用乙二醯氯試劑形成亞胺離子中間體，再加入具有sp-, sp2-, sp3-混成碳的格里納試劑進行親核加成反應，製備一系列二號位具有取代的α-胺基酸衍生物。藉由1H NMR進行α-胺基酸衍生物脫羰基反應中間物的監測，確認脫羰基反應的發生，並計算亞胺離子中間體的轉換率，以此優化後續加成反應的最佳反應時間。此脫碳基反應可應用於生物鹼的合成，本研究利用相較於文獻中簡化的合成步驟，成功製備出尼古丁 (nicotine)、毒芹鹼 (coniine)、毒藜鹼 (anabasine) 及N-methylconnine等四種天然生物鹼，拓展了反應的應用性。In this thesis, we discuss the decarbonylation reaction of N-alkylated cyclic α-amino acid derivatives to form the corresponding iminium intermediates, followed by the use of the sp-, sp2-, sp3-Grignard reagent for nucleophilic addition reaction, to enable the synthesis of a series of 2-substituted α-amino acid derivatives. The decarbonylation reaction can be monitored by 1H NMR to confirm the formation of the iminium intermediates and the conversion yields can be estimated, which allowed us to optimize the reaction time. We also demonstrated that the synthesis of natural alkaloids, such as nicotine, anabaine, coniine and N-methylconnine, with shortest steps and a simplified method to expand the applicability of the reaction.