(69g) Enzymatic Synthesis of Small Chiral Alcohols in One-Phase and Two-Phase Systems

Small enantiomerically pure alcohols are building blocks for pharmaceutical agents and important fine chemical intermediates. Therefore, they are of high commercial interest. However, high enantioselectivities are virtually impossible for the synthesis of small chiral alcohols with chemical catalysts.[1] Due to this, biocatalysis becomes more and more important for those applications. The enzymatic synthesis can be carried out in one-phase and two-phase systems with reaction conditions specially adapted to substrate and enzyme. In one-phase systems for the synthesis of small chiral alcohols the reverse reaction leads to decrease in enantiomeric excess (ee) and in conversion. Furthermore, in one-phase systems hardly water soluble substrates cannot be employed. Utilizing biphasic systems, equilibrium can be shifted to product side by extracting the products back into the non-aqueous phase[2], and racemisation can be supressed as well.[3] Apart from that, higher concentrations of substrates with low H2O solubility can be used (Fig. 1). The non-reactive phase also serves as a reservoir for the reactive phase. On the other hand, non-aqueous media can lead to deactivation of the enzyme. Results will be presented comparing one-phase and two-phase systems employing MTBE as a conventional organic solvent, and task specific ionic liquids (IL).[4] [1] Rissom, S.; Beliczey, J.; Giffels, G.; Kragl, U.; Wandrey, Chr. Tetrahedron: Asymmetry, 1999, 10, 923-928 [2] Eckstein, Marrit F.; Villela Vilho, Murillo; Liese, Andreas; Kragl, Udo Chemical Communication, 2004, 9,1084-1085 [3] Ansorge-Schumacher, Marion; Greiner, Lasse; Schroeper, Florian; Mirtschin, Sebastian; Hischer, Tanja Biotechnology Journal, 2006, 1, 564-568 [4] The kind gift of ionic liquids from Patrick Baeuerlein, University of Eindhoven, Netherlands, is acknowledged. The kind gift of enzymes from S. Na'amnieh and A. Pawlowski, X-Zyme GmbH, Duesseldorf, Germany, is acknowledged.