3-aza-Cope-Mannich cascade reaction for the construction of alkaloid skeletones

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08183
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Meijo University
• Principal Investigator: Takeo Sakai 名城大学, 薬学部, 准教授 (90583873)
• Research Collaborator: Mori Yuji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 3-aza-Cope / Mannich / 連続反応 / イオン対抽出 / 第4級アンモニウム / 転位反応 / アルカロイド

Outline of Final Research Achievements

We developed two types of 3-aza-Cope-Mannich cascade reactions. Based on the ion-pair extraction using tetracyanocyclopentadienide (TCCP) salts, we first synthesized a complex quaternary vinyl ammonium salt which is a starting material of a 3-aza-Cope-Mannich reaction to afford Tricyclic alkaloid skeleton. Next, we examined a cascade reaction involving Gold catalyzed 5-exo-dig cyclization, 3-aza-Cope rearrangement of a spiro vinyl ammonium intermediate, and a Mannich reaction. We successfully obtained a tetracyclic compound including cephalotaxine skeleton. Further studies of the TCCP ion-pair extraction and studies toward the total synthesis of alkaloid natural products are ongoing in our laboratory based on the knowledges obtained by this project.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

有機合成化学領域では取り扱いが困難であった第4級アンモニウム塩を出発原料し、3-aza-Cope-Mannich連続反応という前例のない連続反応で、複雑なアルカロイドの縮環骨格合成法を開発したことが、本研究課題の重要な学術的な意義である。今後、本研究成果を用いたアルカロイド天然物の全合成研究や、従来困難であったビニル第４級アンモニウム塩を原料とする新規反応開発などへの展開が見込まれ、新たな知見を見出す鍵となる発見が行えたと考えている。