Lipase-catalyzed resolution of 4-aryl-substituted β-lactams: Effect of substitution on the 4-aryl ring

Jason A. Carr, Talal F. Al-Azemi, Timothy E. Long, Jeung Yeop Shim, Cristina M. Coates, Edward Turos, Kirpal S. Bisht

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Pseudomonas cepacia lipase (PS-30) was used in hydrolytic resolution of 3-acetoxy-4-aryl-substituted azetidin-2-ones (>97% ee). Twenty-three β-lactam substrates with varied substituents at the C-4 center of the ring were synthesized and subjected to lipase-PS catalyzed hydrolysis in phosphate buffer (pH 7.2, 0.2 M) at 25°C. The reactions occurred with high enantioselectivity and substrate conversion. The effect of substitution on the C-4 aryl ring on lipase hydrolytic activity was dependent upon the steric and electronic nature of the substituent and its position on the aryl ring. The stereopreference of the lipase PS-30 for the (3S,4R) enantiomer was rationalized using a known active site model. Absolute stereochemistry of the enantiomers was established using single crystal X-ray crystallographic techniques.

Original languageEnglish (US)
Pages (from-to)9147-9160
Number of pages14
JournalTetrahedron
Volume59
Issue number46
DOIs
StatePublished - Nov 10 2003
Externally publishedYes

Keywords

  • Enatioselectivity
  • Kinetic resolution
  • Lactam
  • Lipase

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Carr, J. A., Al-Azemi, T. F., Long, T. E., Shim, J. Y., Coates, C. M., Turos, E., & Bisht, K. S. (2003). Lipase-catalyzed resolution of 4-aryl-substituted β-lactams: Effect of substitution on the 4-aryl ring. Tetrahedron, 59(46), 9147-9160. https://doi.org/10.1016/j.tet.2003.09.057