Development of efficient synthetic method of tricyclic humulanolides and structure-activity relationship

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Japan Women's University
• Principal Investigator: ABE Hideki 日本女子大学, 理学部, 教授 (00328551)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 三環性フムラノライド / wilfolide B / ラジカル環化反応 / 異性化反応 / 閉環メタセシス

Outline of Final Research Achievements

With the aim of studying the structure-activity relationship of humulene-based tricyclic fumulanolides, development of an efficient synthetic method for them. After synthesizing an aldehyde having a Z-unsaturated ester from 2,2-dimethyl-1,3-propanediol as a starting material, the radical cyclization using samarium iodide afforded the bicyclic lactone. Then, two types of side chains were constructed for the bicyclic lactone via introduction of a butenyl group at the lactone carbonyl α position, and an isomerization was performed to adjust the stereochemistry. Finally, the construction of the 8-membered ring by ring closing metathesis followed by catalytic hydrogenation allowed us to achieve the first total synthesis of wilfolide B.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

今回確立した三環性フムラノライド wilfolide B の全合成経路は、類似した三環性化合物の合成を可能とするため、今後構造活性相関研究への展開を期待させる成果が得られたものと考えている。またそこから生まれる新しい知見は、フムラノライド類の利用価値を判別するための材料の１つになるものと思われることから、今回の成果は非常に意義深い成果であると考えられる。