Large-scale stereoselective enzymatic ketone reduction with in situ product removal via polymeric adsorbent resins

Abstract 3,4-methylene-dioxyphenyl acetone was stereoselectively reduced to the corresponding S-3,4-methylene-dioxyphenyl isopropanol in >95% isolated yield and >99.9% enantiomeric excess (ee). The NAD(P)H-dependent enzymatic activity within living Zygosaccharomyces rouxii was utilized to accomplish this reaction. Since the substrate and product were both toxic to Z. rouxii, polymeric hydrophobic resins were used to both supply substrate to and remove the product from the reaction mixture as it formed. This approach allowed the reaction concentration to be increased from 6 to 40 g l−1. The reaction was scaled-up to a volume of 300 l by utilizing a commercially available agitated filter as a reactor. This reactor design allowed the reaction, product isolation, and resin recycle to be accomplished within a single piece of equipment. The overall reactor productivity was 75 g l−1 day−1.