Basic Studies and Synthetic Application of Enzyme Functions
Grant-in-Aid for Overseas Scientific Survey.
|Research Institution||Kyoto University|
FUJI Kaoru Institute for Chemical Research, Kyoto University, 化学研究所, 教授 (20027056)
TORBJORN Nor ストックホルム王立工科大学, 教授
川端 猛夫 京都大学, 化学研究所, 助手 (50214680)
田中 圭 京都大学, 化学研究所, 助教授 (50093266)
村井 章夫 北海道大学, 理学部, 教授 (20000838)
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
NORIN Torbjorn Department of Organic Chemistry, Royal Institute of Technology, Sweden
MURAI Akio Faculty of Science, Hokkaido University
TANAKA Kiyoshi Institute for Chemical Research, Kyoto University
|Project Fiscal Year
1991 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1992 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1991 : ¥2,500,000 (Direct Cost : ¥2,500,000)
|Keywords||Lipase / Peroxidase / Meso-aziridine / Cis-disubstituted aziridine / Unusual Amino Acids / Bestatin, / Unsaturated diol / Brometherification / リパーゼ / ペルオキシダーゼ / メソ-アジリジン / シス-ジ置換アジリジン / 異常アミノ酸 / ベスタチン / 不飽和ジオール / ブロモエーテル化 / リパ-ゼ / エステル交換反応 / アジリジン / アミノアルコ-ル|
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.
Research Output (9results)