猪胰脂肪酶催化外消旋P-手性α-羟基磷酸酯类化合物的动力学拆分

Kinetic Resolution of Racemic P-Chiralα-Hydroxymethylphosphonates Catalyzed by Lipase from Porcine Pancreas

酶催化具有高效、高选择性以及反应条件温和等优点,已经成为有机合成领域的重要方法.研究了P-手性α-羟基磷(膦)酸酯类化合物的合成方法.在猪胰脂肪酶的催化作用下,外消旋α-羟基磷(膦)酸酯与乙酸乙烯酯之间能够顺利地发生酯交换反应,以高达49%的产率和83%的ee值得到相应的手性产物,且该反应在非常温和的条件下就能够进行.同时,在计算机的辅助下建立了酶-底物之间的结合模型,通过对接的方法揭示了反应中酶催化对映选择性的机理.

The development of enzyme-catalyzed methods for the synthesis of P-chiral phosphine derivatives has important implications.Herein this work presents a direct biocatalytic transesterification of racemicα-hydroxyphosphonates and vinyl acetate,which provides a rapid access to P-chiral hydroxymethylphosphonates.Catalyzed by lipase from porcine pancreas(PPL),which is commercially available,the reactions proceed efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides in up to 49%yield and 83%ee under very mild conditions.The enzyme-substrate binding mode was established and the high enantioselectivity of PPL was revealed through docking simulations.