Creation of Artificial Biocatalysts with NHC and Application to Organic Synthesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 25288078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Okayama University
• Principal Investigator: Ema Tadashi 岡山大学, 自然科学研究科, 教授 (20263626)
• Project Period (FY): 2013-04-01 – 2019-03-31
• Keywords: 生体触媒 / 有機触媒 / 含窒素複素環式カルベン / 無溶媒

Outline of Final Research Achievements

We created an artificial biocatalyst capable of catalyzing the C-C bond formation. To enable the binding to the catalytic serine residue of the active site of a lipase, NHC precursor 1 bearing a phosphate group (transition-state analog) was synthesized in 13 steps. Artificial biocatalyst CALB-1 was obtained by mixing 1 with a lipase, and it catalyzed the asymmetric benzoin reaction. We also demonstrated that enzymatic properties such as enantioselectivity could be controlled by the chemical modification of the I287C variant of a lipase. We also found that the catalyst loading of NHC can be reduced under solvent-free conditions. Even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2 mol%), and even semi-solid state organocatalysis took place.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

C-C結合形成反応を触媒できる汎用酵素は極めて希である。生体触媒は、環境に優しく持続的発展を可能にする技術の１つであるが、C-C結合形成反応を触媒できるものが少ないため、これを打破する革新的手法が待ち望まれていた。本研究では、C-C結合形成反応を触媒できる活性種として含窒素複素環式カルベン（NHC）を選択し、NHC前駆体をタンパク質反応場であるリパーゼに導入することにより、人工生体触媒を創成し、実際にC-C結合形成反応を触媒することを確認した。C-C結合形成反応を触媒する人工生体触媒を創成できることを実証した本研究の意義は極めて大きい。