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

E. Forró, Zsolt Galla, F. Fülöp

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 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. An efficient enzymatic two-step cascade procedure was devised for CAL-B-catalysed hydrolysis of racemic N-hydroxymethyl-β-lactams. Conditions in which the hydroxymethyl group serves as a traceless activating group (E > 200), giving desired β-amino acid along with unreacted starting lactam enantiomers (ee > 95 %) were identified; polymerization was controlled by addition benzylamine addition.

Original languageEnglish
Pages (from-to)2647-2652
Number of pages6
JournalEuropean Journal of Organic Chemistry
Volume2016
Issue number15
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • Amino acids
  • Cascade reaction
  • Enantioselectivity
  • Enzyme catalysis
  • Hydrolysis
  • Lactams
  • Traceless activating group

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

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