Enzymatic Transformations 62. Preparative Scale Synthesis of Enantiopure Glycidyl Acetals using an Aspergillus niger Epoxide Hydrolase-Catalysed Kinetic Resolution

The hydrolytic kinetic resolution of five glycidaldehyde acetal derivatives was examined using the recombinant Aspergillus niger epoxide hydrolase as biocatalyst. This could successfully be performed, at room temperature, using solely demineralised water as solvent and following a two‐phase methodology allowing us to operate at a global substrate concentration as high as 200 g/L in the reactor. The observed E values were shown to be modest to excellent, depending on the structure of the acetal moiety, indicating that it is possible to achieve this resolution very efficiently just by choosing the right substituents. Both the unreacted (R)‐epoxide and the formed (S)‐diol could thus be obtained in good to excellent ee (ee>99 % for the epoxide). For the best substrates, the reaction could be performed within a few hours by using a biocatalyst over substrate molecular ratio of about 9 to 10×10−4 mol %. The turnover frequency (TOF) as well as the total turnover number (TON) of the enzyme proved to be excellent as compared to chemical catalysts – reaching respectively values in the order of 6×102 mol sub/mol enz/min and 6×104 mol sub/mol enz. The space‐time yield of the best (two‐phase) reactor could thus reach a value as high as 56 g/L/hour. As a demonstration experiment, a 50‐g scale resolution of glycidaldehyde 2,2‐dimethyltrimethylene acetal was performed.