Development of manganese-catalyzed aerobic oxidative transformations for finding bioactive compounds

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06944
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Kitasato University
• Principal Investigator: Yamamoto Daisuke 北里大学, 薬学部, 講師 (10509970)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 酸化反応 / マンガン錯体 / 環境調和性 / アミノペルオキシ化反応 / イソオキサゾリン環

Outline of Final Research Achievements

Molecular oxygen (O2) is an abundant and environmentally friendly oxidant due to its continuous production through photosynthesis. Therefore, recently, the development of catalytic oxidative transformations that incorporate oxygen atoms from the air into a substrate has attracted research and industrial attention.
In this study, we achieved the stereoselective oxygenative aminoperoxidation of N-(but-3-en-1-yloxy)arylsulphonamides. Several hydroxymethylated isoxazolidines were obtained in high yields by directly incorporating O2 from the air (pure oxygen was not required) and using only a low-loading Mn(III) complex (1.0-1.5 mol%) in EtOH as an environmentally friendly solvent. All reaction processes could be conducted in open air without cooling, heating or high pressure. Considering the simplicity of operation, wide range of substrates and mild reaction conditions, this novel reaction is a promising synthetic approach for synthesising hydroxymethylated isoxazolidines.

Free Research Field

化学系薬学

Academic Significance and Societal Importance of the Research Achievements

再生可能な資源である空気中の酸素分子を酸素源として利用する分子変換法は、これまで有機酸化物や無機酸化物に依存していた酸化反応を一新しうるものであり、持続可能な社会の実現に求められる技術の一つとして注目されている。今回我々が本申請課題を通じて開発した触媒的酸素付加型アミノペルオキシ化反応は、医薬品や天然物などに広く存在するイソオキサゾリジン環を合成できる方法論である。本手法は、EtOH中、基質に対し僅か1 mol%のマンガン錯体を添加するのみで、窒素－炭素結合形成と酸素分子の付加を一挙に進行させることができる操作性の優れた環境調和性の高い分子変換法である。