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-2enoates, 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.

The synthesis of enantio-and diastereomerically pure g-butyrolactones is described using a one-pot, two-enzyme cascade. Ethyl 2-methyl-4-oxoA C H T U N G T R E N N U N G pent-2-enoate (2) was reduced selectively first in a 1,4-reduction using the old yellow enzyme (OYE1) [EC 1.6.99.1] and consecutively in a 1,2-reduction by an alcohol dehydrogenase [EC 1.1.1.2].

No abstract