The N‐Hydroxymethyl Group as a Traceless Activating Group for the CAL‐B‐Catalysed Ring Cleavage of β‐Lactams: A Type of Two‐Step Cascade Reaction

Abstract

AbstractAn efficient enzymatic two‐step cascade procedure has been devised for rapid access to diverse amino acids from N‐hydroxymethyl‐β‐lactams; representative amino acids include the antifungal agent cispentacin, intermediates for the taxol side‐chain, and assorted cathepsin inhibitors. When CAL‐B‐catalysed hydrolyses of racemic N‐hydroxymethyl‐β‐lactams were performed with H2O (0.5 equiv.) in iPr2O at 60 °C, relatively quick (vs. non‐activated counterparts) and enantioselective (E > 200) ring cleavage reactions took place. As the ring‐opened amino acids formed, the hydroxymethyl group, as a traceless activating group, underwent spontaneous in situ degradation. Consequently, the desired β‐amino acid and unreacted N‐hydroxymethyl‐β‐lactam enantiomers (ee > 95 %) were formed. The formation of polymers, induced by liberation of formaldehyde, was successfully restricted by the addition of benzylamine as a capture agent, to the enzymatic reactions.