Total synthesis of cycloartane-type triterpenoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02131
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Tsukano Chihiro 京都大学, 農学研究科, 准教授 (70524255)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 合成化学 / 生物有機化学 / 有機化学 / 全合成 / 生理活性 / 構造活性相関

Outline of Final Research Achievements

Pre-schisanartanin A and lancilactone C are triterpenoids, isolated from Schisandra chinensis and Kadsura lancilimba, respectively, which exhibit broad-spectrum antiviral activity, but their cytotoxicity is very weak, making them valuable as pharmaceutical seed compounds. In this study, we developed an efficient synthetic strategy for cycloartane skeletons based on a domino [4+3] cycloaddition involving cleavage of a three-membered ring. By developing this synthetic strategy, we succeeded in constructing the characteristic 7-membered triene structure of lancilactone C (proposed structure) and achieved its total synthesis. Based on NMR data and proposed biosynthesis of lancilactone C, the proposed structure was revised, and its revised structure was elucidated by further synthesis. Additionally, the left and right fragments of pre-schisanartanin A containing an all cis-substituted propane were also synthesized.

Free Research Field

有機化学・天然物化学

Academic Significance and Societal Importance of the Research Achievements

現在、複雑な構造を有するトリテルペノイドは、天然物合成研究の最先端にあり、新しい合成戦略と新規生物活性物質の創出の場となっている。本研究においても、ドミノ[4+3]環化付加反応を開発した点や、特異な置換パターンを有する三員環を含む構造の新規合成法を確立した点で、学術的意義はきわめて大きい。本合成法の創出は、シクロアルタン型トリテルペノイドlancilactone Cの世界初の全合成と真の構造解明につながり、これにより自然界からごく微量しか得られない複雑かつ新奇なトリテルペノイドの確実な供給法を確立したことに加えて、多置換３員環や不飽和７員環をもつ生理活性物質を合成するための新しい指針を得た。