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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
Author(s) -
Forró Enikő,
Galla Zsolt,
Fülöp Ferenc
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600234
Subject(s) - chemistry , hydroxymethyl , enantioselective synthesis , stereochemistry , benzylamine , cleavage (geology) , ring (chemistry) , amino acid , enantiomer , medicinal chemistry , catalysis , organic chemistry , biochemistry , geotechnical engineering , fracture (geology) , engineering
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.