Enzymatic resolution of 4-N-phenylacetylamino-derivatives obtained from multicomponent reactions using PenG amidase and in silico studies

Dirk Strübing, Helfried Neumann, Stefan Klaus, Axel Jacobi Von Wangelin, Dirk Gördes, Matthias Beller, Paolo Braiuca, Cynthia Ebert, Lucia Gardossi, Udo Kragl

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The three component coupling reaction of aldehydes, phenylacetamide and dienophiles gave the corresponding N-phenylacetamidocyclohexene derivatives in good yields (55-70%) and high regioselectivity. For the first time, enzymatic kinetic resolution of this class of compounds has been achieved. The enantioselective hydrolysis of 4-N-phenylacetylamino-cis-3a,4,7,7a- hexahydroisoindole-1,3-dione derivatives using Penicillin G amidase (PGA) from Escherichia coli gave the remaining enantiomer with ee-values from 30 to 70% at 50% conversion. On the basis of molecular modeling predictions, 1-N-phenylacetylamino-2-cyano-5-cyclohexene derivatives were synthesized. The kinetic resolution resulted in ees up to 99%. The differences of the observed selectivities confirmed the in silico predictions based on the simulation of enzyme-substrate interactions.

Original languageEnglish
Pages (from-to)683-691
Number of pages9
JournalTetrahedron
Volume60
Issue number3
DOIs
StatePublished - 12 Jan 2004
Externally publishedYes

Keywords

  • Hydrolases
  • Modelling
  • Multicomponent reaction
  • Penicillin G amidase

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