Lipase-catalyzed resolution of 4-aryl-substituted β-lactams

Effect of substitution on the 4-aryl ring

Jason Alexander 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 Citations (Scopus)

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

Fingerprint

Lactams
Lipase
Substitution reactions
Enantiomers
Burkholderia cepacia
Stereochemistry
Enantioselectivity
Substrates
Hydrolysis
Catalytic Domain
Buffers
Phosphates
X-Rays
Single crystals
X rays

Keywords

  • Enatioselectivity
  • Kinetic resolution
  • Lactam
  • Lipase

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

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

Lipase-catalyzed resolution of 4-aryl-substituted β-lactams : Effect of substitution on the 4-aryl ring. / Carr, Jason Alexander; Al-Azemi, Talal F.; Long, Timothy E.; Shim, Jeung Yeop; Coates, Cristina M.; Turos, Edward; Bisht, Kirpal S.

In: Tetrahedron, Vol. 59, No. 46, 10.11.2003, p. 9147-9160.

Research output: Contribution to journalArticle

Carr, JA, Al-Azemi, TF, Long, TE, Shim, JY, Coates, CM, Turos, E & Bisht, KS 2003, 'Lipase-catalyzed resolution of 4-aryl-substituted β-lactams: Effect of substitution on the 4-aryl ring', Tetrahedron, vol. 59, no. 46, pp. 9147-9160. https://doi.org/10.1016/j.tet.2003.09.057
Carr, Jason Alexander ; Al-Azemi, Talal F. ; Long, Timothy E. ; Shim, Jeung Yeop ; Coates, Cristina M. ; Turos, Edward ; Bisht, Kirpal S. / Lipase-catalyzed resolution of 4-aryl-substituted β-lactams : Effect of substitution on the 4-aryl ring. In: Tetrahedron. 2003 ; Vol. 59, No. 46. pp. 9147-9160.
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