Kitamoto Yuichi, Kuruma Yosuke, Suzuki Kazumi, Hattori Tetsutaro
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan.
J Org Chem. 2015 Jan 2;80(1):521-7. doi: 10.1021/jo502521e. Epub 2014 Dec 3.
The Candida antarctica lipase B (CAL-B) catalyzed kinetic resolution of primary and secondary alcohols via acetylation is dependent on the permittivity (ε) of the reaction solvent. For example, the enantiomeric ratio (E) vs ε plot for the acetylation of 1-(naphth-2-yl)ethanol (1) exhibits a convex shape, taking the maximum E value at a medium ε value (11.2), whereas the same plot for the acetylation of benzyl 3-hydroxybutylate (3) exhibits a concave shape, taking the minimum E value at a similar ε value (11.6). Kinetic studies reveal that the difference in shape of the E vs ε plots originates from the relative reaction rate between the enantiomers with different Michaelis constants (Km). Thus, when the enantiomer with a larger Km value in the middle ε region reacts more slowly than its antipode, the ε dependence of E exhibits a convex shape. On the other hand, when the enantiomer reacts more quickly, it exhibits a concave shape. The E vs ε plot for the acetylation of 2-methoxy-2-phenylethanol (7) exhibits a convex shape with the maximum E value (20) at ε = 14.1. The E value can be further improved to almost reach the efficiency required for industrial applications (E ≈ 30) by the addition of a nitro compound.
南极假丝酵母脂肪酶B（CAL-B）催化的伯醇和仲醇通过乙酰化进行的动力学拆分取决于反应溶剂的介电常数（ε）。例如，1-（萘-2-基）乙醇（1）乙酰化反应的对映体比例（E）与ε的关系图呈凸形，在中等ε值（11.2）时达到最大E值，而苄基3-羟基丁酸酯（3）乙酰化反应的相同关系图呈凹形，在相似的ε值（11.6）时达到最小E值。动力学研究表明，E与ε关系图形状的差异源于具有不同米氏常数（Km）的对映体之间的相对反应速率。因此，当在中等ε区域中具有较大Km值的对映体反应比其对映体慢时，E对ε的依赖性呈凸形。另一方面，当对映体反应更快时，它呈凹形。2-甲氧基-2-苯基乙醇（7）乙酰化反应的E与ε关系图呈凸形，在ε = 14.1时达到最大E值（20）。通过添加硝基化合物，E值可进一步提高，几乎达到工业应用所需的效率（E≈30）。
