Asymmetric Synthesis of N-Alkyl Amino Acids through a Biocatalytic Dynamic Kinetic Resolution of PEGylated N-Alkyl Amino Esters

Org Lett. 2023 Dec 15;25(49):8927-8931. doi: 10.1021/acs.orglett.3c03784. Epub 2023 Dec 5.

Abstract

The first examples of a practical procedure for a lipase-catalyzed dynamic kinetic resolution of PEGylated N-alkyl amino esters is reported. This method allows for the preparation of a broad range of aromatic and aliphatic enantiomerically enriched N-alkyl unnatural amino acids in up to 98% yield and 99% ee. We have found that PEGylated esters have a significant solubility advantage and improved reactivity over traditional hydrophobic lipase substrates, thereby allowing for efficient and scalable dynamic kinetic resolution (DKR) under aqueous conditions.

MeSH terms

  • Amino Acids* / chemistry
  • Catalysis
  • Esters* / chemistry
  • Kinetics
  • Lipase / metabolism
  • Polyethylene Glycols
  • Stereoisomerism

Substances

  • Esters
  • Amino Acids
  • Lipase
  • Polyethylene Glycols