Toward stereocontrolled, chemoenzymatic synthesis of unnatural peptides

An efficient, chemoenzymatic method for the multicomponent synthesis of unnatural tripeptides is presented. Development of a previously described procedure combines the diversity offered by multicomponent reactions with the selectivity of biocatalysts and allows the convenient introduction of varied amino acid moieties into the tripeptide scaffold, with control of the stereochemistry. Additionally, it allows the introduction of a methyl group to the amide nitrogen, leading to derivatives of N-methylated amino acids.