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

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.