Berendsen W R, Gendrot G, Freund A, Reuss M
Institute of Biochemical Engineering (IBVT), University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Biotechnol Bioeng. 2006 Dec 5;95(5):883-92. doi: 10.1002/bit.21034.
Lipase-catalyzed kinetic resolution of racemates is a popular method for synthesis of chiral synthons. Most of these resolutions are reversible equilibrium limited reactions. For the first time, an extensive kinetic model is proposed for kinetic resolution reactions, which takes into account the full reversibility of the reaction, substrate inhibition by an acyl donor and an acyl acceptor as well as alternative substrate inhibition by each enantiomer. For this purpose, the reversible enantioselective transesterification of (R/S)-1-methoxy-2-propanol with ethyl acetate catalyzed by Candida antarctica lipase B (CAL-B) is investigated. The detailed model presented here is valid for a wide range of substrate and product concentrations. Following model discrimination and the application of Haldane equations to reduce the degree of freedom in parameter estimation, the 11 free parameters are successfully identified. All parameters are fitted to the complete data set simultaneously. Six types of independent initial rate studies provide a solid data basis for the model. The effect of changes in substrate and product concentration on reaction kinetics is discussed. The developed model is used for simulations to study the behavior of reaction kinetics in a fixed bed reactor. The typical plot of enantiomeric excess versus conversion of substrate and product is evaluated at various initial substrate mixtures. The model is validated by comparison with experimental results obtained with a fixed bed reactor, which is part of a fully automated state-of-the-art miniplant.
脂肪酶催化外消旋体的动力学拆分是合成手性合成子的一种常用方法。这些拆分反应大多是受可逆平衡限制的反应。首次提出了一种用于动力学拆分反应的广泛动力学模型，该模型考虑了反应的完全可逆性、酰基供体和酰基受体对底物的抑制作用以及每种对映体的替代底物抑制作用。为此，研究了南极假丝酵母脂肪酶B（CAL-B）催化的（R/S）-1-甲氧基-2-丙醇与乙酸乙酯的可逆对映选择性酯交换反应。这里提出的详细模型适用于广泛的底物和产物浓度范围。经过模型判别并应用霍尔丹方程降低参数估计中的自由度后，成功确定了11个自由参数。所有参数同时拟合到完整数据集。六种类型的独立初始速率研究为该模型提供了坚实的数据基础。讨论了底物和产物浓度变化对反应动力学的影响。所开发的模型用于模拟研究固定床反应器中反应动力学的行为。在各种初始底物混合物下评估对映体过量与底物和产物转化率的典型关系图。通过与使用固定床反应器获得的实验结果进行比较来验证该模型，该固定床反应器是最先进的全自动小型工厂的一部分。
