Development of a Novel Chiral Piperidine Construction Method Utilizing Multi-component Linkage Reactions and Total Synthesis of Alkaloids

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14620
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Chiba University
• Principal Investigator: Shiomi Shinya 千葉大学, 大学院薬学研究院, 特任助教 (20892805)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 有機合成化学 / 天然物化学 / アルカロイド

Outline of Final Research Achievements

The first asymmetric total synthesis of huperzine H was successfully accomplished by heating 1 equivalent of KHMDS and a crown ether in toluene. This reaction represents a valuable methodology for the synthesis of natural products with challenging 9-membered ring structures. The research findings were published in the Journal of Organic Chemistry, a renowned journal of the American Chemical Society, and were highlighted as the cover picture.

Furthermore, a novel piperidine ring construction reaction utilizing an organocatalyst was developed, enabling the efficient synthesis of synthetic intermediates that can be further transformed into various alkaloids. The results of this research were presented at the Kanto Branch Meeting of the Pharmaceutical Society of Japan and the Annual Meeting of the Pharmaceutical Society of Japan, providing valuable insights into the development of this synthetic route.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって抗アルツハイマー活性などが知られているリコポジウムアルカロイドの仲間であるフペルジンHの初の不斉全合成を達成し、その相対および絶対立体配置を全て明らかにした。合成によって得られたフペルジンHは学内共同研究の生物活性試験サンプルとして提供し、薬理活性を調査中である。