Development of peptide catalysts based on library screening and machine learning

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05487
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kudo Kazuaki 東京大学, 生産技術研究所, 教授 (80251669)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ペプチド触媒 / 面不斉化合物 / グアニジン触媒 / 不斉触媒反応

Outline of Final Research Achievements

Regarding the proposal to find some kind of correlation between the amino acid sequence of the peptide catalyst and its catalytic reaction result, which was originally planned, it was not possible to draw a clear conclusion.
On the other hand, we could discover a new N-terminal guanidinylated strongly basic peptide asymmetric catalyst that non-covalently activates substrates, and used it to a Michael addition of β-dicarbonyl compounds to nitroolefins with high enantioselectivity. Furthermore, it was found that the kinetic resolution proceeded with high efficiency when planar chiral [2.2]paracyclophane with a 2-nitrovinyl group was used as the substrate.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

グアニジンにキラルな置換基を結合させた強塩基性不斉触媒はこれまでに報告例があるものの，決まってグアニジンが2本以上の結合を介して不斉源とつながった形をしていた。今回我々が見出したペプチド触媒は，グアニジンが1本の結合のみで不斉源とつながった構造をもち，このことによってかさ高い基質の反応を触媒できることが示された。また，面不斉化合物の速度論的光学分割では，一般の低分子触媒ではほとんどキラリティーの認識ができないことが判明し，この点でもペプチド触媒という新しいタイプの有機触媒の有用性を示すことができた。