Stereoselective Enzyme Cascades: An Efficient Synthesis of Chiral γ-Butyrolactones

A one-pot consecutive two-enzyme sequential cascade toward chiral γ-butyrolactones using an enoate reductase as well as alcohol dehydrogenases in combination with a glucose dehydrogenase is reported. In this scalable process, the products were obtained in high yield (up to 90%) and with perfect enantioselectivity (98→99% ee). The starting materials, ethyl 4-oxo-pent-2-enoates, are readily accessible via Wittig-type reactions. Furthermore, the stereoselectivity of the enoate reductase catalyzed reaction has been studied in detail, leading to deeper insights into the mechanism of this enzyme.