Institute of Biochemical and Biomedical Engineering, Chang Gung University, Kwei-Shan, Tao-Yuan, 33302, Taiwan.
Bioprocess Biosyst Eng. 2012 Aug;35(6):953-62. doi: 10.1007/s00449-012-0680-x. Epub 2012 Jan 17.
A new approach to the lipase-catalyzed hydrolytic resolution of (R,S)-azolyl carbamates for obtaining chiral azolyl carbamates and alcohol is described. With (R,S)-1-phenylethyl azolyl carbamates as the model substrates, the best reaction condition of using (R,S)-1-phenylethyl 4-bromopyrazole carbamate (1) as the substrate in water-saturated diisopropyl ether at 45 °C is selected. The kinetic constants, and hence enantiomeric ratio of 124, are then estimated from the kinetic analysis by considering the alcohol inhibition effect, with which theoretical time-course conversions for both enantiomers are numerically solved and agree with the experimental data. The thermodynamic parameters -ΔΔH and -ΔΔS satisfying a linear enthalpy-entropy compensation relationship of -ΔΔS = -38.84 + 3.29(-ΔΔH) are further estimated. An extension of the resolution platform to (R,S)-4-bromopyrazole carbamates derived from other (R,S)-alcohols (4, 5, 7) is also addressed.
本文描述了一种新的脂肪酶催化（R，S）-唑基氨基甲酸酯的水解拆分方法，用于获得手性唑基氨基甲酸酯和醇。以（R，S）-1-苯基乙基唑基氨基甲酸酯为模型底物，选择在 45°C 的水饱和二异丙醚中使用（R，S）-1-苯基乙基 4-溴吡唑基氨基甲酸酯（1）作为底物的最佳反应条件。然后通过考虑醇抑制效应，从动力学分析中估算出动力学常数，从而估计出对映体比率 124，由此数值求解了两种对映体的理论时程转化率，并与实验数据相符。进一步估计了满足线性焓熵补偿关系-ΔΔS=-38.84+3.29(-ΔΔH)的热力学参数-ΔΔH 和-ΔΔS。还扩展了拆分平台，以用于由其他（R，S）-醇（4、5、7）衍生的（R，S）-4-溴吡唑基氨基甲酸酯。
