Expanding the medicinally relevant chemical space with architecturally complex natural products and their synthetic analogues

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H06110
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Biomolecular chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Inoue Masayuki 東京大学, 大学院薬学系研究科(薬学部), 教授 (70322998)
• Co-Investigator(Kenkyū-buntansha): 櫻井 香里 東京農工大学, 工学(系)研究科(研究院), 准教授 (50447512)
• Project Period (FY): 2017-05-31 – 2022-03-31
• Keywords: 合成化学 / 全合成 / 天然物 / 生物活性分子の設計 / 生理活性

Outline of Final Research Achievements

Architecturally complex natural products with molecular weight of over 500 often exhibit potent bioactivities, and represent privileged structures for the development of pharmaceuticals. We achieved many total syntheses of the complex terpenes, nucleosides, and peptides. The developed strategies and tactics significantly simplified the synthetic routes to the natural products, thereby facilitating their practical preparations. Furthermore, a medicinally relevant chemical space was expanded by the preparation of numerous natural product analogues, leading to the discovery of new artificial analogues with higher or disparate bioactivities. Structure-activity relationship studies of these analogues enabled us to determine biologically significant structural features and to elucidate their mode of actions. The thus-obtained results together will serve as valuable information for the synthesis and design of novel molecules with more potent and selective biological activities.

Free Research Field

天然物合成化学、生物有機化学

Academic Significance and Societal Importance of the Research Achievements

分子量が500を超える巨大複雑天然物は、一般的な医薬品よりも強力な活性を有する。しかし、巨大複雑天然物の機能は未解明であり、創薬に応用されていなかった。本研究成果は、分子の形状を自由自在に操ることができる有機化学を進歩させ、創薬プロセスの飛躍的な加速、巨大複雑天然物の創薬応用に繋がる革新的なものである。医薬品の開発、生体機能の新しい解析法の開発や一般原理の解明に寄与するため、広範な科学技術・公衆衛生分野に大きな意義を持つ。