壹.吲啶生物鹼的全合成研究 貳.氮上具烷基取代脯胺酸進行脫羰基反應中間物的鑑定

(1)Synthetic Study toward Indolizidine Alkaloids. (2)Identification of Reactive Intermediates for the Decarbonylative Reaction of 1-Alkylprolines.

王瀞暄(Wang Jing-Shiuan)

指導教授 ： 簡敦誠

國立臺灣師範大學/理學院/化學系/碩士(2017年)

https://doi.org/10.6345/NTNU202203417

摘要

本論文研究主題共分兩部分。
第一部分主要使用相較於文獻中相對簡化的合成步驟以實驗室開發的仿生合成方法製備吲啶生物鹼。以氮上具苯甲基取代的脯胺酸為起始物與草酸醯氯形成的亞胺離子，與3’,4’-二甲氧基苯乙酮進行分子內Mannich反應以製備2位為benzoylmethylene取代的pyrrolidine。並進行氮上具苯甲基取代的2-benzoylmethylene pyrrolidine去除保護基以製備ruspolinone的探討。而架構吲啶的關鍵步驟是以天然物ruspolinone進行醯胺合成後，接著進行分子內Aldol反應製備。最後將醯胺上羰基還原為亞甲基製備吲啶生物鹼。
第二部分探討使用氮上具苯甲基取代脯胺酸與乙二醯氯形成亞胺離子後，與未經活化的C-H親核試劑進行Mannich反應來制備pyrrolizidine -位具有取代的反應機制。在我們的研究結果中顯示1-alkyl-1-pyrrolinium為具有反應活性的中間體。而azomethine ylide雖然並未涉入脫羧基Mannich反應中，但可以藉由1-benzyl-1-pyrrolinium在鹼性條件下，進行去質子化來製備。

關鍵字

吲啶 ； 分子內Mannich反應 ； 仿生合成

並列摘要

This master's thesis contains two research topics.
The first topic focuses on the development of a biomimetic synthesis method which is relatively simple compared to the literature’s synthetic steps to the synthesis of indolizidine alkaloids. A concise strategy includes a construction of 2-benzoylmethylene pyrrolidine by a direct formation of pyrrolinium intermediates from N-benzylproline and subsequent intermolecular Mannich reactions with 3’,4’-dimethoxyacetophenone to form N-benzylruspolinone. Subsequently, the removal of the benzyl group afforded ruspolinone. The crucial indolizidine-ring closure was accomplished by amide formation at the pyrrolidine and followed by intramolecular Aldol reaction. Finally, the reduction of the amide carbonyl group to methylene furnished the indolizidine alkaloids
The final topic described the mechanistic study for the decarbonylative reaction of 1-benzylprolines with oxalyl chloride followed by the Mannich reaction with unactivated C-H nucleophiles to form 2-substituted pyrrolidines. Our study showed that 1-alkyl-1-pyrrolinium is the reactive intermediate. The results also confirmed that the azomethine ylide, although it was not involved in the decarbonylative Mannich reaction, can be generated by deprotonation of 1-benzyl-1-pyrrolinium under basic condition.

並列關鍵字

indolizidine alkaloids ； intermolecular Mannich reactions ； biomimetic synthesis ； ruspolinone

參考文獻

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