One-Pot Lipase-Catalyzed Enantioselective Synthesis of (R)-(-)-N-Benzyl-3-(benzylamino)butanamide: The Effect of Solvent Polarity on Enantioselectivity

Molecules. 2017 Dec 9;22(12):2189. doi: 10.3390/molecules22122189.


The use of the solvent engineering has been applied for controlling the resolution of lipase-catalyzed synthesis of β-aminoacids via Michael addition reactions. The strategy consisted of the thermodynamic control of products at equilibrium using the lipase CalB as a catalyst. The enzymatic chemo- and enantioselective synthesis of (R)-(-)-N-benzyl-3-(benzylamino)butanamide is reported, showing the influence of the solvent on the chemoselectivity of the aza-Michael addition and the subsequent kinetic resolution of the Michael adduct; both processes are catalyzed by CalB and both are influenced by the nature of the solvent medium. This approach allowed us to propose a novel one-pot strategy for the enzymatic synthesis of enantiomerically enriched β-aminoesters and β-aminoacids.

Keywords: aza-Michael addition; chemoselectivity; enantioselectivity; lipase promiscuity; solvent engineering; stereoselectivity.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism*
  • Benzylamines / chemistry
  • Biocatalysis
  • Crotonates / chemistry
  • Lipase / metabolism*
  • Solvents
  • Stereoisomerism
  • Thermodynamics


  • Amino Acids
  • Benzylamines
  • Crotonates
  • Solvents
  • Lipase