Ghanem Ashraf
Department of Organic Chemistry, University of Geneva, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland.
Org Biomol Chem. 2003 Apr 21;1(8):1282-91. doi: 10.1039/b301086d.
The use of enzymes as valuable catalysts in organic solvents has been well documented. However, some of their features limit their application in organic synthesis, especially the frequently lower enzyme activity under nonaqueous conditions, which constitutes a major drawback in the application of enzymes in organic solvents. In addition, many enzymatic reactions are subject to substrate or product inhibition, leading to a decrease in the reaction rate and enantioselectivity. To overcome these drawbacks and to make enzymes more appealing to organic chemists, we demonstrate the use of cyclodextrins as regulators for the Pseudomonas cepacia lipase (PSL) and macrocyclic additives to enhance the reaction rate and enantioselectivity E in lipase-catalyzed enantioselective transesterification of 1-(2-furyl)ethanol in organic solvents. Both reaction rate and enantioselectivity were significantly enhanced by several orders of magnitude when using co-lyophilized lipase in the presence of cyclodextrins. The effect of cyclodextrin derivatives as well as solvents on the improvement of the reaction parameters has been studied. The observed enhancement was tentatively interpreted in terms of their ability to give a certain flexibility to the enzyme and to form a host-guest complex, thus avoiding product inhibition and leading to enhancement of the reaction rate and enantioselectivity. The effect of cyclodextrin additives on the enzyme morphology has been studied using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) of the co-lyophilized lipase with cyclodextrins. The ability of cyclodextrins to form a host-guest complex to avoid product inhibition, which leads to the observed enhancement, has been proved by NOESY, COSY, 13C and 1H NMR.
酶作为有机溶剂中有价值的催化剂的应用已有充分记载。然而，它们的一些特性限制了其在有机合成中的应用，尤其是在非水条件下酶活性常常较低，这是酶在有机溶剂中应用的一个主要缺点。此外，许多酶促反应会受到底物或产物抑制，导致反应速率和对映选择性降低。为了克服这些缺点并使酶对有机化学家更具吸引力，我们展示了使用环糊精作为洋葱假单胞菌脂肪酶（PSL）的调节剂以及大环添加剂来提高在有机溶剂中脂肪酶催化的1-(2-呋喃基)乙醇对映选择性酯交换反应的反应速率和对映选择性E。当在环糊精存在下使用共冻干脂肪酶时，反应速率和对映选择性均显著提高了几个数量级。研究了环糊精衍生物以及溶剂对反应参数改善的影响。观察到的增强作用初步解释为它们赋予酶一定灵活性并形成主客体复合物的能力，从而避免产物抑制并导致反应速率和对映选择性提高。使用扫描电子显微镜（SEM）和与环糊精共冻干脂肪酶的能量色散X射线（EDX）研究了环糊精添加剂对酶形态的影响。通过NOESY、COSY、13C和1H NMR证明了环糊精形成主客体复合物以避免产物抑制的能力，这导致了观察到的增强作用。
