Efficient Preparation of Optically Active Highly Strained Azirines and Synthesis of Natural and Unnatural Amines and Amino Acids

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12450366
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: SAKAI Takashi Okayama University, Faculty of Engineering, Professor, 工学部, 教授 (00170556)
• Co-Investigator(Kenkyū-buntansha): KORENAGA Toshinobu Okayama University, Faculty of Engineering, Assistant Professor, 工学部, 助手 (70335579) ; EMA Tadashi Okayama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (20263626)
• Project Period (FY): 2000 – 2002
• Keywords: azirine / optically active / lipase / asymmetric synthesis / enzyme / amino acid / low-temperature reaction / aziridine

Research Abstract

Stereoselective reactions starting from azirines have been developed. In the hydrogenation of aziridine, which was synthesized by the reaction of azirine with AlMe_3, the ring-opening reaction took place at the 3-position specifically to give only β-amino alcohol. Whether the stereochemistry at the 3-position was retained or inverted depended on the solvent used. An interesting correlation was found between the dielectric constants of the solvents and the diastereomeric excess values (% de). We also succeeded in the synthesis of new azirine carboxylic acid ester. Β-Keto ester was reacted with hydroxyl amine to give the corresponding oxime. Treatment with tosyl chloride and triethylamine afforded the new azirine carboxylic acid ester.
Although the reaction rate of the lipase-catalyzed kinetic resolution of azirine at -40 ℃ was improved by using lipase immobilized to porous ceramics support, the enantioselectivily was decreased as compared to that obtained with the lipase on Celite. Vario us acylating agents were examined to improve the enantioselectivity. Using vinyl butyrate, the E value was increased up to 96, and the catalytic turnover number was improved by more than 10-fold.
We have previously found in the lipase-catalyzed kinetic resolution that lowering the reaction temperature results in an increase in enantioselectiviry. In this study, we found that the enantioselectivity is increased according to a thermodynamic equation, but below a critical temperature, the enantioselectivity is decreased according to another equation. We call this temperature "the inversion temperature". In the kinetic resolution of azirine, the change of solvent resulted in the change of the inversion temperature. Furthermore, the change of lipase also resulted in the shift of the inversion temperature. The correlation between the inversion temperatures and various parameters of the solvents was investigated. To investigate the salvation mode for azirine, low-temperature NMR spectra were measured. As a result, complicated factors that are affected by the kinds of lipase and substrate seemed to be responsible for the inversion temperature.

Research Products

• [Publications] Sakai, T., Hayashi, K., Yano, F., Takami M., Ino, M., Korenaga, T., Ema, T.: "Enhancement of the Efficiency of the Low Temperature Method for Kinetic Resolution of Primary Alcohols by Optimizing the Organic Bridges in Porous Ceramic-Immobilized Lipase"Bull.Chem.Soc.Jpn.. (印刷中).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sakai, T., Hayashi, K., Yano, F., Takami, M., Ino, M., Korenaga, T., Ema, T.: "Enhancement of the Efficiency of the Low Temperature Method for Kinetic Resolution of Primaty Alcohols by Optimizing the Organic Bridges in Porous Ceramic-Immobilized Lipase"Bull. Chem. Soc. Jpn.,. in press. (2003)
  • Description: 「研究成果報告書概要(欧文)」より