Catalytic Asymmetric Synthesis for the Next Generation Drug Discovery

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14878
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: NODA Hidetoshi 公益財団法人微生物化学研究会, 微生物化学研究所, 主任研究員 (40771738)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 不斉触媒 / β-アミノ酸 / ペプチド / 含窒素複素環

Outline of Final Research Achievements

This research project aimed at the development of new catalytic reactions for the synthesis of b2-amino acids. Readily available, substituted isoxazolidin-5-ones were selected as substrates. The efforts in this project has led to two classes of transformations: direct catalytic asymmetric Mannich-type reactions and traceless CH functionalizations. The former reaction was well suited for the synthesis of complex, linear b2,2-amino acids, whereas the latter was for cyclic b2-amino acids otherwise difficult to obtain. The cyclization process was triggered upon the generation of alkyl nitrene species that has not been documented well in the literature, opening up a new avenue to the chemistry of the reactive intermediate.

Free Research Field

有機化学

Academic Significance and Societal Importance of the Research Achievements

医薬品開発効率の向上が強く叫ばれる近年の創薬化学研究では，「新規」かつ「ドラッグライク」な化合物をこれまで以上に迅速に供給，試験する必要がある．本研究で得られた構造的に多様な新規アミノ酸類はこのような要請に応えるビルディングブロックとして，有機合成化学の観点から創薬化学研究を大きく変革するに資する化合物である．