Some Items of Interest to Process R&D Chemists and Engineers

Amide bond formation remains a cornerstone of pharmaceutical synthesis, with more than half of the top-selling smallmolecule drugs containing at least one amide linkage.To address the sustainability and atom economy limitations associated with conventional amide coupling strategies, Lei and co-workers contributed to the development of a novel biocatalytic approach based on engineered oxidative amidases (OxiAms) (Science, DOI: 10.1126/science.adw3365).Through multiple rounds of protein engineering, aldehyde dehydrogenases were successfully repurposed to catalyze the direct oxidative amidation of aldehydes and amines.Strategic mutations increased the hydrophobicity of the catalytic pocket, enabling selective capture of thioester intermediates by nucleophilic amines rather than water.The resulting enzyme platform demonstrated broad substrate tolerance, providing access to more than 70 amide products from diverse aldehyde and amine partners.The methodology was further expanded into a one-pot, two-step synthesis from alcohols by integrating an alcohol dehydrogenase with an NAD + recycling system.Its practical relevance was validated through gram-scale synthesis and the shortened de novo preparation of valuable pharmaceutical targets, highlighting its potential for sustainable drug manufacturing. ■ CATALYST-AND BASE-FREE ELECTROCHEMICAL ORTHO AMINATION OF PHENOLSConventional routes to N-alkyl aryl amines typically require multistep sequences usually involving nitro group reduction followed by N-alkylation, leading to lengthy processes and reduced overall sustainability.To support the identification of more efficient synthetic alternatives, Liu, Wang, and coworkers reported an electrochemical methodology enabling the direct amination of arenes under catalyst-free and base-free conditions (Chem.Commun., DOI: 10.1039/d6cc01670g).The approach leverages electrochemical activation to generate reactive intermediates without the need for additional reagents, Highlights from the Literature pubs.acs.org/OPRD