Diversified artificial natural products extracts by photo-reaction

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19191
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry and related fields
• Research Institution: Chiba University
• Principal Investigator: Arai Midori 千葉大学, 大学院薬学研究院, 准教授 (40373261)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 天然物 / 光環化反応 / ロカグラミド / Wnt / がん

Outline of Final Research Achievements

Extract of natural resources is a mixture of unknown diversified natural products. In this research, we aimed the synthesis of new natural products mixture by photo-cyclized reaction. Although several MeOH extracts of plants were irradiated by UV lamp with olefin compounds, unfortunately reproducibility was low. Therefore, synthesis of rocaglamides with fluorous tag was examined. We also succeeded in synthesizing of rocaglamide derivatives with heterocycles. They showed strong Wnt signal inhibitory activity. Moreover, biotin-tagged rocaglamides retained the Wnt signal inhibitory activity.

Free Research Field

天然物化学，ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究では生薬エキスを用いて光環化付加反応を検討した．光反応を用いたエキス有機合成は初の試みであった．また，光環化付加反応を用いて種々のヘテロ環ロカグラミド誘導体の合成に成功し，それらが，がんで異常亢進しているWntシグナルに対する阻害作用を有していることを見いだした．この結果は，ヘテロ環含有ロカグラミドの新規生物活性を見いだした学術的意義もさることながら，ロカグラミド誘導体が新規抗がん剤リードになる可能性を示唆しており，社会的意義があるものと考えている．