Development of comprehensive approach to the synthesis of flavonoid via novel nucleophilic aromatic substitution reaction

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15468
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: University of Shizuoka
• Principal Investigator: SHIGETA TAKASHI 静岡県立大学, 食品栄養科学部, 助教 (00779225)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 芳香族求核置換反応 / フラボノイド / フラバン-3-オール / 電子豊富芳香族 / 網羅的合成

Outline of Final Research Achievements

Natural flavonoids which are multiple electron-donating groups substituted aromatic compounds potent several properties. However, it is difficult that the flavonoid compounds with various substitution pattern are synthesized with uniform method. Comprehensive synthesis is one of the most effective strategy to provide a specific group of natural products from widely usable substrates. Recently novel nucleophilic aromatic substitution reaction (SNAr reaction) was developed in our laboratory. In this study, new SNAr reaction was applied to the synthesis of flavan-3-ol derivatives. Synthetic method of fluorobenzene derivatives (1) and epoxy compounds (2) was developed. Subsequently, cyclization precursors (4) were synthesized from substrates 1 and 2. Furthermore, compounds 5 with flavan-3-ol structure was obtained by developed SNAr reaction.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

本法は、SNAr 反応が抱える「基質に依存した反応性」を改善する手法である点が学術的に興味深いだけでなく、天然物合成に対してより効率的な合成ルートを開発するための鍵となりうる。天然に存在するフラボノイド類は 2 万種を超える一方で、ほとんどのフラボノイドはそれぞれの有する機能性が明らかにされていない。フラボノイド類の網羅的な合成法を開発することでライブラリーが構築されれば、機能性解析の研究を進める際に望みの天然物を容易に利用できるようになる。機能性の解析が進むことで食品に含まれるフラボノイド類の健康効果が明らかとなり、食品の新たな付加価値を発掘することや社会の健康増進に寄与することができる。