Isolation and synthetic studies on Lycopodium alkaloids towards the remedy for Alzheimer disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Chiba University
• Principal Investigator: Kogure Noriyuki 千葉大学, 薬学研究科(研究院), 助教 (80396689)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アルカロイド / リコポジウム / 構造決定 / 不斉全合成

Outline of Final Research Achievements

Because of the aging society, the discovery of new remedies for memory disorder (or Alzheimer disease) is urgent business in Japan.Some Lycopodium alkaloids are known to have acetylcholine esterase (AChE) inhibitory activity. This research was aimed for the discovery of Lycopodium alkaloids which have strong activity against AChE by separation from Lycopodium plants and total synthesis from commercially available reagents.
As a result, we have isolated many Lycopodium alkaloids from L. carinata and L. nummulariforium, distributed in Thailand, and elucidated their structures by spectroscopic analyses and chemical conversions. Furthermore, we have achieved the total syntheses of natural Lycopodium alkaloids utilizing our original strategy. The shortest total synthesis of lycodine was accomplished by a strategy featuring the one-pot construction of a tetra cyclic lycodine skeleton from a linear precursor, which was inspired by the biosynthetic consideration of Lycopodium alkaloids.

Free Research Field

天然物化学