Enantioselective hydrolysis of 3,4-disubstituted β-lactams. An efficient enzymatic method for the preparation of a key Taxol side-chain intermediate

Zsolt Galla, Ferenc Beke, Eniko Forró, Ferenc Fülöp

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

3,4-Disubstituted β-lactams 3-benzyloxy-4-(4-chlorophenyl)azetidin-2-one [(3S∗,4R∗)-(±)-1], 3-benzyloxy-4-phenylazetidin-2-one [(3S∗,4R∗)-(±)-2] and 4-(4-chlorophenyl)-3-phenoxyazetidin-2-one [(3S∗,4R∗)-(±)-3] were resolved through immobilized CAL-B-catalysed ring-cleavage reactions. Excellent enantioselectivities (E > 200) were obtained for (3S∗,4R∗)-(±)-1 and (3S∗,4R∗)-(±)-2 when the reactions were performed with added H2O as nucleophile in tert-butyl methyl ether at 70 °C, whereas only moderate E (12) was achieved for (3S∗,4R∗)-(±)-3 under the same conditions but in diisopropyl ether. The resulting ring-opened β-amino acids [(2R,3S)-4 (ee > 98%), (2R,3S)-5 (ee > 98%) and (2R,3S)-6 (ee = 50%)] and the unreacted β-lactams [(3S,4R)-1-3] (ee > 98%) could be easily separated.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalJournal of Molecular Catalysis B: Enzymatic
Volume123
DOIs
Publication statusPublished - Jan 1 2016

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Keywords

  • Candida antarctica lipase B
  • Enzyme catalysis
  • Ring-cleavage
  • Taxol
  • ß-amino acid

ASJC Scopus subject areas

  • Catalysis
  • Bioengineering
  • Biochemistry
  • Process Chemistry and Technology

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