Synthetic study of Andrastin C with high density of quaternary asymmetric carbons aiming at the elucidation of its mode of action

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: University of Shizuoka
• Principal Investigator: Yoshimura Fumihiko 静岡県立大学, 薬学部, 准教授 (70374189)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アンドラスチン / ブラシリカルジン / 全合成 / 四級不斉炭素 / シアノ基 / ニトリル / シアノエン反応

Outline of Final Research Achievements

This research aimed at the asymmetric total syntheses of Andrastin C and Brasilicardins A-D which belong to biologically active natural products with multiple quaternary asymmetric carbon atoms. To achieve this goal, new methods for stereoselective construction of a quaternary asymmetric carbon atom were developed by using an intramolecular conjugate addition of a cyano anion and an intramolecular cyano ene reaction. By using them as key reactions, we accomplished the asymmetric total syntheses of Brasilicardin A-D. In addition, we developed the stereoselective synthesis of the AB-ring and BCD-ring units of Andrastin C.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

複雑な構造をもつ天然物の合成は、既存の反応の単純な組み合わせでは不可能である。本研究では、シアノ基の特性に着目した合成反応の開発と四級不斉炭素が密集した天然物の全合成への展開を行った。独自の合成戦略で複雑構造天然物ブラシリカルジン類の網羅的不斉全合成を実現し、学術的意義は大きい。また、新反応の実用性を天然物全合成で実証できたため、有機合成化学の進展にも寄与できたと考えている。