1997 Fiscal Year Final Research Report Summary
Synthesis of Multi-functional Chiral Molecules by Developing the Function of Biocatalysts
| Project/Area Number |
07455362
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Okayama University |
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Principal Investigator |
UTAKA Masanori Okayama University, Faculty of Engineering, Professor, 工学部, 教授 (30033153)
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| Co-Investigator(Kenkyū-buntansha) |
TSUBOI Sadao Okayama University, Faculty of Environmental Science and Technology, Professor, 環境理工学部, 教授 (00032954)
EMA Tadashi Okayama University, The Graduate School of Natural Science and Technology, Resea, 大学院・自然科学研究科, 助手 (20263626)
SAKAI Takashi Okayama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (00170556)
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| Project Period (FY) |
1995 – 1997
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| Keywords | bakers'yeast / reductase / asymmetric reduction / biocatalyst / lipase / optically active |
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| Research Abstract |
1. Highly Stereoselective Synthesis of Polyfunctional Chiral Building Blocks
A reductase that shows reducing activity toward 1-chloro-2-hexanone was purified from bakers'yeast cell-free extract by means of chromatographic separations in 4 steps. Reductants with high optical purity were obtained.
Highly enantioselcective kinetic resolutions of several chiral building blocks were accomplished by the lipase-catalyzed transesterifications.
2. Artificial Improvement of the Enantioselectivity
We incidentally discovered that a small amount of organic solvent can affect the enantioselectivity in the bakers'yeast reduction of 1-chloro-2,4-alkanediones. By using organic solvent, inhibitor, and heat treatment, the 6% ee was increased up to 94% ee.
In the lipase-catalyzed transesterification in organic solvent, the acyl-enzyme intermediate is in situ formed. By changing the acyl donor, the structure of the acyl-enzyme is also changed, which is expected to change the enantioselectivity. Examination of this concept to 2-substituted cyclopentenols resulted in the change of the E values.
The lipase-catalyzed transesterifications were performed at various temperatures ranging from 30 to -60ﾟC.As a result, the enantioselectivity was increased with decrease of the temperature. Plot of 1nE against 1/T afforded a straight line, from which DELTADELTAH^<<double plus>> and DELTADELTAS^<<double plus>> values were calculated according to a theoretical equation.
3. Origin of the Enantioselectivity
Kinetic study revealed that chiral recognition in the binding step is unimportant for the enantioselectivity but that chiral discrimination operates at the transition state. Stereoelectronic theory was applied to the lipase-catalyzed reaction and molecular orbital calculations were performed on a model reaction. A transition -state model to rationalize the enantioselectivity was proposed.
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Research Products
(14 results)
