Development of Boropeptide Chemistry Based on Asymmetric C-H Borylation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21183
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Sawamura Masaya 北海道大学, 理学研究院, 教授 (40202105)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: アミノボロン酸 / ボロペプチド / 不斉合成

Outline of Final Research Achievements

An asymmetric C-H boration reaction was attempted using peptide compounds with various structures as reaction substrates, but due to the difficulty in synthesizing the substrate and to the fact that the boration reaction did not proceed as expected, we did not obtain any useful results. Regarding the synthesis of medium molecular peptides containing unnatural amino acids, it was found that the reaction between an alkylboronate and an isocyanate proceeded efficiently under the reaction conditions using a rhodium catalyst. In the palladium-catalyzed reaction of aryl halides, the sterieochemistry of the coupling reaction is reversed depending on whether the reaction substrate is a boronate produced from a secondary amide or a tertiary amide. However, as the above studies proceeded, it gradually became clear that the reproducibility of the C-H boration reaction was not good, resulting in a significant delay in the progress of the research.

Free Research Field

有機金属化学

Academic Significance and Societal Importance of the Research Achievements

アミノ酸のカルボキシル基がボロン酸で置換された化合物はボロアミノ酸と呼ばれ、これを含むペプチド系化合物（ボロペプチド）は医薬原体として実際に利用されている。現在は分子量が小さなボロペプチドが開発されているが、中分子領域でのボロペプチドの機能には大きな可能性が期待されるところである。本研究では通常のペプチドの主鎖C-H結合の直接ホウ素化活性を種々検討し、今後の研究に活用可能な有用な情報が得られた。また、αーイソシアノメチルボロネート及びその誘導体を用いるボロペプチド合成法について検討した結果から、有機ホウ素化合物の化学的性質を理解する上での有用な情報が得られた。