Front Cover: Streamlining Vorinostat Synthesis: A Chemoenzymatic Continuous Flow Approach (Eur. J. Org. Chem. 27/2025)

Abstract

The Front Cover shows suberanoyl hydroxamic acid (SAHA), also known as vorinostat, a histone deacetylase (HDAC) inhibitor approved by the FDA for the treatment of patients with cutaneous T-cell lymphoma. To date, most of the developed synthetic approaches require halogenated solvents, as well as work-up and purification steps to isolate the desired hydroxamic acid. In their Research Article (DOI: 10.1002/ejoc.202500178), S. Princiotto and co-workers describe a new chemo-enzymatic preparation that employs more eco-friendly solvents and avoids tedious and expensive purification procedures. The synthesis was optimized under continuous-flow conditions, starting from suberanoyl acid (first train). Reaction with O-tetrahydropyranyl hydroxylamine (NH₂OTHP, boarding platform) is biocatalyzed by CaLB lipase (tunnel). The drop-off point represents the acidic resin responsible for acetal cleavage, that is, deprotection of the O-THP moiety. Pure vorinostat arrives at the final station (VORINOSTATION) 4 hours after boarding without any intermediate stops.