Efficient Two-Step Synthesis of Nor(pseudo)ephedrines Using Immobilized Biocatalysts

Nor(pseudo)ephedrine (N(P)E) isomers, belonging to the amphetamine class of ephedra alkaloids, are naturally occurring substances found in plants such as Catha edulis (khat) and various Ephedr a species. Besides their biological activity as sympathomimetics, N(P)Es are valuable in termediates in pharmaceutical synthesis, also serving as auxiliaries and ligands in asymmetric organic reactions [1,2]. Traditional chemical approaches for the asymmetric synthesis of N (P)Es are often complex, thus achieving high yields and optical purity poses significant challenges [3]. A two-step biocatalytic method for synthesizing (1S)-N(P)Es was recently proposed by some of the authors [4]. This approach relies on a benzoin-type condensation catalyzed by the acetoin oxidoreductase (Ao:DCPIP OR) from Bacillus licheniformis, followed by a transamination step mediated by an amine transaminase ((S)- or (R)-ATA). However, enzyme stability under reaction conditions, along with challe nges in enzyme recovery and reuse, remain significant limitations. To address these issues, we immobilized Ao:DCPIP OR and ATAs and assessed their performance in terms of yield, stability, and recyclability. The two-step biotransformation catalyzed by the immobilized enzymes allowed to obtain (1S)-N(P)Es with hi gh conversion and optical purity [5].