1992 Fiscal Year Final Research Report Summary
Basic Studies and Synthetic Application of Enzyme Functions
| Project/Area Number |
03044077
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kyoto University |
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Principal Investigator |
FUJI Kaoru Institute for Chemical Research, Kyoto University, 化学研究所, 教授 (20027056)
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| Co-Investigator(Kenkyū-buntansha) |
TORBJORN NOR ストックホルム王立工科大学, 教授
KAWABATA Takeo Institute for Chemical Research, Kyoto University, 化学研究所, 助手 (50214680)
TANAKA Kiyoshi Institute for Chemical Research, Kyoto University, 化学研究所, 助教授 (50093266)
MURAI Akio Faculty of Science, Hokkaido University, 理学部, 教授 (20000838)
NORIN Torbjorn Department of Organic Chemistry, Royal Institute of Technology, Sweden
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| Project Period (FY) |
1991 – 1992
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| Keywords | Lipase / Peroxidase / Meso-aziridine / Cis-disubstituted aziridine / Unusual Amino Acids / Bestatin, / Unsaturated diol / Brometherification |
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| Research Abstract |
Enzymes such as esterase, lipase, and oxidase promote fundamental and important reactions in the living systems. In this research, we have developed the synthetic applications of these enzymes.
1. Conversion of meso-aziridines into optically active cis-disubstituted aziridines by enzymatic transesterification.
Cis-disubstituted aziridines are important class of compounds since they are the consituents of antitumor agents such as mytomycin C and FR-900482 and also they play a key role on the antitumor activity. Meso-aziridine derivatives are readily prepared from commercially available cis-2-butene-1,4-diol. Transformation of the meso-derivatives into the optically active ones was carried out with a nucleophile (butanol) in oraganic solvent (diisopropyl ether) in the presence of the enzyme. Among a variety of lipases and esterases screened, readily available and cheep lipase, Amano P, has proved to highly enantioselective in catalyzing the transesterification reactions (95-98%ee). Optically active cis-disubstituted aziridines are expected to be useful precursors of unusual amino acids. Threo-beta-amino alcohols were obtained by the ring-opening reaction of aziridines through intramolecular attack of a hydroxy group. The amino alcohols were then transformed to the unusual amino acids which are the key constituents of biologically active peptides such as bestatin and apthanin G.
2. Peroxidase-promoted transformation of unsaturated diols into cyclic ethers.
A variety of unsaturated diols were transformed into cyclic ethers in the presence of lactoperoxidase (LPO) and sodium bromide. Structures of the precursor diols determined the mode of cyclization. Thus, five-membered cyclic ethers and eight- membered cyclic ethers were regioselectively formed, respectively. A bicyclic natural bromo ether, laureatin, have been also transformed from the original precursor, (3Z,6S,7S)-laurediol by LPO.
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