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

An 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 H 2 O (0.5 equiv.) in i Pr 2 O 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.