Analysis of terpene cyclization reactions based on computational chemistry, synthetic organic chemistry, and biochemistry

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K14791
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: University of Yamanashi
• Principal Investigator: Sato Hajime 山梨大学, 大学院総合研究部, 特任助教 (80782648)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: テルペン / 計算化学 / 天然物化学

Outline of Final Research Achievements

In this study, the mechanism of terpene cyclase was analyzed using experimental and computational chemistry. Artificial substrates with trifluoromethyl groups were synthesized to elucidate the role of the Me group and the effect of increased electrophilicity of the carbocation and decreased electron density of the double bond on the cyclization reaction. The biosynthetic reaction mechanism of spiroalbatene and peniroquesine was also elucidated. This research has both an engineering significance of deep understanding of the mechanism of terpene cyclization and its application to “manufacturing by learning from nature” and a significance of pursuing the basic science of the reactivity of carbocation. As research results, one review article and three original papers have been published.

Free Research Field

計算化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、テルペン環化反応における反応制御機構の解明を目的とし、CF3基を有する人工基質を用いて、カルボカチオンと低求核性二重結合の反応性、およびMe基の役割を明らかにすることを目指しています。この研究は、従来の実験科学的手法に加え、最新の計算化学を組み合わせた独自のアプローチを採用しており、学術的に新規性と独創性を有しています。本研究成果により、自在にテルペン化合物を生産する酵素設計や、低環境負荷型物質生産によるSDGsへの貢献の可能性を秘めています。さらに、CF3基を有する環化生成物は、新規医薬品リード化合物や新規機能性分子としての応用が期待されるため、社会的意義も大きいと考えられます。